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26042017
1
Sicherheitsbeurteilung neuartiger LebensmittelHaslberger SS 2017
bull Einfuumlhrung Sicherheit Risiko Hazard WHO Codexbull Substantial equivalent intended- unintended Effectsbull Geschichte Ziele der Lebensmittelproduktion Entwicklungen Pflanzen Tiere MObull Values in der Interaktion Mensch Umweltbull Spezifische Aspekte GVOs Gentransfer Allergie CRISPR Klonierenbull Lebensmittel -zutaten mit neuer Struktur aus nicht traditionellen Rohstoffen
fremden Kulturkreisen Neue technische Verfahren an traditionellen Lebensmittelnbull Regelungen Novel food traceability labelling 200118 18292013 18302003bull Umwelt Cartagena Protokoll Trade regulationsbull Sicherheitsbewertung Risk assessment Elemente Toxikologiebull Health claim fuctional food personalised Nutrition Epigeneticbull Vortraumlge zu Beispielen
Food is not safe in principle ( WHO ) As safe as Blickweisen
26042017
2
Was zu Regeln wozu
Umwelt Gesundheit Food Feed Produkt
Denkmodelle
Wie zu regeln
CODEX Alimentarius
Development of scientifically sound
international standards and norms for
consumer health protection and fair food
trade practices
WHO Risk Analysis in general
Risk Assessment Risk Management
Risk Communication
Process Initiation
Science based Policy based
Interactive exchange
of information and opinions
concerning risks
Uncertainty
26042017
3
CODEX CODEX
Definitionen
Hazard Eigenschaften eines Stoffes oder Mischung von
Stoffen die bei der Herstellung beim Gebrauch oder der
Entsorgung negative Auswirkungen auf den Organismus oder
die Umwelt haben koumlnnen
Risiko Risiko ist die Moumlglichkeit dass ein schaumldigendes
Ereignis unter bestimmten Bedingungen aufgrund der
Exposition chemischer oder physikalischer Stoffe auftritt oder
die zu erwartende Haumlufigkeit des Auftretens eines
schaumldigenden Ereignisses
Hazard qualitativer Begriff
Risiko quantitativer Begriff
bull Risikobewertung
bull Strukturierter Prozess
bull Ziel Charakterisierung der Natur und der
Wahrscheinlichkeit eines negativen Resultats
bull basiert auf wissenschaftlichen Erkenntnissen
bull transparent objektiv nachvollziehbar
Risk assessment
26042017
4
Risk assessment
bull Identifikation der Gefahren
bull Charakterisierung der Gefahren
bull Expositionsabschaumltzung
bull Charakterisierung der Risiken
Hazard identification ndash Gefahrenidentifizierung
bull Identifikation von bekannten oder unbekannten
Gesundheitsgefahren in Verbindung mit einer bestimmten
Substanz
bull biologische (Mikroorganismen wie zB Salmonellen
Listerien)
bull chemische (Pestizide Tierarzneimittel Schwermetalle
usw)
bull physikalische Gefahren (Fremdkoumlrper wie zB Steine
Glas
Prinzipien des Risk assessment
Prinzipien des Risk assessment
Hazard characterisation ndash Gefahrencharakterisierung
bull bestimmt Erreger und moumlgliche Nebenwirkungen
bull qualitative undoder quantitative Bewertung
bull chemische Stoffe dose-response-assessment
bull biologische oder physikalische Stoffe dose-response-
assessment wenn die Daten vorliegen
bull Daten aus wissenschaftlicher Forschung toxikologischen
epidemiologische Studien und Statistiken
Exposure assessment ndash Expositionsabschaumltzung
bull qualitative undoder quantitative Bewertung des
Ausmaszliges eines Erregers
bull gesamte aktuelle Exposition der Bevoumllkerung
bull basiert auf der Verknuumlpfung von Verzehrsdaten
bestimmter Lebensmittel mit dem Vorhandensein der
Substanz in den betroffenen Lebensmitteln
Prinzipien des Risk assessment
26042017
5
Prinzipien des Risk assessment
Risk characterisation ndash Risikocharakterisierung
Integration von hazard identification hazard characterization
and exposure assessment in einer Schaumltzung der
Nebenwirkungen inklusive der auftretenden Unsicherheiten
die in der Population auftreten koumlnnen
Plant Selection
Agriculture begins with the collection and planting of seeds from wild plants
Occurs in 8 locations throughout the world between 7000 -12000 years ago
Selections were made based on yield seed size and taste
7
Biotechnology and Agriculture development
Landraces Diversity
10
Refers to the particular kinds of old seed strains and varieties that are farmer-selected in areas where local subsistence agriculture has long prevailed Landraces are highly adapted to specific locales or groups
Definition modified by native and also immigrant farmers
The term is usually applied to varieties of corn squash and beans that were domesticated by native farmers
GREEN Revolution
13
Term coined by US Agency 1968) Movement to increase yields by using New crop cultivars Irrigation Fertilizers Pesticides Mechanization A planned international effort funded by Rockefeller Foundation Ford Foundation Many developing country governments Purposed to eliminated hunger by improving crop performance Norman Borlaug ( 1970 Nobel price)
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6
T Malthus 1766- 1834Crisis in food production
12
Models for population growth and food security
Pessimistic or Alarmist Theory
Malthus - 19th century Coale amp Hoover (1958)
Paul Ehrlich (Population Bomb)
Meadows (Limits to Growth) ndash 1960s and 1970s
Focus on population policy amp fixed non-renewable resources
Optimistic Theory
Ester Boserup ndash 1960s ndash 70s (agric Intensification)
Julian Simon ndash 1970s - 80s (human capital)
Neutralist or Revisionist Theory
Pflanzenzuumlchtung
Breeding yield time for development
29
Klassische Zuumlchtungsmethoden
AuslesezuumlchtungSelektionszuumlchtungDie Auslesezuumlchtung faumlngt mit dem Anbau von Genotypengemischen (vorh genetische Linien auch Wildpflanzen) an Aus dem nach gemeinsamer Abbluumlte erzeugten Saatgut werden Pflanzen mit vorteilhaften Eigenschaften ausgewaumlhlt (Zuchtwahl Massenauslese) KombinationszuumlchtungDie Kombinationszuumlchtung ist eine Kreuzung verschiedener Genotypen (Linien) Es entsteht ein neuer Genotyp
HeterosiszuumlchtungIn der Heterosiszuumlchtung werden bei Fremdbefruchtern (Mais Roggenhellip) in mehrjaumlhriger Zuumlchtung aus heterozygoten Ausgangspflanzen nahezu homozygote Inzuchtlinien gezuumlchtet Kreuzt man zwei solche Linien tritt bei der F1 Generation oft eine auffallende Mehrleistung gegenuumlber der Elternformen auf Dies nennt man bdquoHeterosis-Effekt
HybridzuumlchtungDie Hybridzuumlchtung ist ein Beispiel fuumlr Heterosiszuumlchtung zur Erzielung einer hohen markt- oder betriebsgerechten pflanzlichen Produktion durch Bastardwuumlchsigkeit So werden bei der Hybridzuumlchtung geeignete gesondert gezuumlchtete Inzuchtlinien einmalig miteinander gekreuzt (Einfachhybride) [1] Die Nachkommen der ersten Generation (F1) einer solchen Kreuzung haben gegenuumlber der Elterngeneration ein uumlppigeres Wachstum (HeterosiseffektFuumlr den Landwirt bedeutet dies jedoch dass das Saatgut jedes Jahr wieder neu bezogen werden muss wenn er den Ertragsvorteil gegenuumlber Nicht-Hybriden weiterhin erhalten will da der Heterosiseffekt nur in der F1-Generation auftritt und danach wieder verloren geht
MutationszuumlchtungBei der Mutationszuumlchtung werden Samen Roumlntgen- oder Neutronenstrahlen Kaumllte- und Waumlrmeschocks oder anderen Mutagenen ausgesetzt[2] um neue Eigenschaften durch Mutation zu erzielen die einen positiven Effekt aufweisen Damit wird die Zuumlchtung neuer Sorten erheblich beschleunigt
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Hybridzuumlchtung Heterosis Hybrid Heterosis effect
Introducing new traits in a plant family(Random) Mutation Breeding
67
IAEA
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8
Breeding Irradiation
Irradiator at Institute of
Radiation Breeding Ibaraki-ken JAPAN (httpwwwirbaffrcgojp)
68
Mutation breeding
69
Tissue culture Clones
70
Somaclonal variation
Production of a new variety of japanese
butterbur using somaclonal variation(uppernew variety lowernative variety)
71
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9
Tomoffel Breeding using transposons
72
Ein Transposon ist ein DNA-Abschnitt bestimmter Laumlnge im Genom der seine Position im Genom veraumlndern kann (Transposition) Man unterscheidet Transposons deren mobile Zwischenstufe von RNA gebildet wird (Retroelemente oder Klasse-I-Transposon) von denjenigen deren mobile Phase DNA ist (DNA-Transposon oder Klasse-II-Transposon)
Transposon tagging
The molecular isolation of transposable elements now permits the cloning of genes in which the element resides The major advantage of this system is that genes whose function is not known can be cloned
75
Molecular marker directed breeding
73
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10
Bio-Technology
INTEGRATED Pest Management A modern Way of Agriculture
74
Cloning Definition
Cloning is the process of making an identicalcopy of something
In biology it collectively refers to processesused to
-- copies of DNA Fragments (molecular cloning)-- cells (cell cloning)-- organism
The term also covers when organisms such as bacteria insectsor plants reproduce asexually
DNA cloning
To clone a piece of DNA DNAis cut into fragments usingrestriction enzymes thatrecognize specific sequencesof bases in DNA Thefragments are pasted intovectors that have been cut bythe same restriction enzymeVectors (eg plasmids orviruses) are needed to transferand maintain DNA in a hostcell
Reproductive Cloning
Reproductive cloning is a technology used to generate an animal thathas the same nuclear DNA as another currently or previously existinganimal Dolly was created by reproductive cloning technology In aprocess called somatic cell nuclear transfer (SCNT) scientists transfergenetic material from the nucleus of a donor adult cell to an egg whosenucleus has been removed The reconstructed egg containing the DNAfrom a donor cell must be treated with chemicals or electric current inorder to stimulate cell division Once the cloned embryo reaches asuitable stage it is transferred to the uterus of a female host where itcontinues to develop until birth
26042017
11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
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12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
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13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
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14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
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15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
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16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
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17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
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CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
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GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
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21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
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22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
2
Was zu Regeln wozu
Umwelt Gesundheit Food Feed Produkt
Denkmodelle
Wie zu regeln
CODEX Alimentarius
Development of scientifically sound
international standards and norms for
consumer health protection and fair food
trade practices
WHO Risk Analysis in general
Risk Assessment Risk Management
Risk Communication
Process Initiation
Science based Policy based
Interactive exchange
of information and opinions
concerning risks
Uncertainty
26042017
3
CODEX CODEX
Definitionen
Hazard Eigenschaften eines Stoffes oder Mischung von
Stoffen die bei der Herstellung beim Gebrauch oder der
Entsorgung negative Auswirkungen auf den Organismus oder
die Umwelt haben koumlnnen
Risiko Risiko ist die Moumlglichkeit dass ein schaumldigendes
Ereignis unter bestimmten Bedingungen aufgrund der
Exposition chemischer oder physikalischer Stoffe auftritt oder
die zu erwartende Haumlufigkeit des Auftretens eines
schaumldigenden Ereignisses
Hazard qualitativer Begriff
Risiko quantitativer Begriff
bull Risikobewertung
bull Strukturierter Prozess
bull Ziel Charakterisierung der Natur und der
Wahrscheinlichkeit eines negativen Resultats
bull basiert auf wissenschaftlichen Erkenntnissen
bull transparent objektiv nachvollziehbar
Risk assessment
26042017
4
Risk assessment
bull Identifikation der Gefahren
bull Charakterisierung der Gefahren
bull Expositionsabschaumltzung
bull Charakterisierung der Risiken
Hazard identification ndash Gefahrenidentifizierung
bull Identifikation von bekannten oder unbekannten
Gesundheitsgefahren in Verbindung mit einer bestimmten
Substanz
bull biologische (Mikroorganismen wie zB Salmonellen
Listerien)
bull chemische (Pestizide Tierarzneimittel Schwermetalle
usw)
bull physikalische Gefahren (Fremdkoumlrper wie zB Steine
Glas
Prinzipien des Risk assessment
Prinzipien des Risk assessment
Hazard characterisation ndash Gefahrencharakterisierung
bull bestimmt Erreger und moumlgliche Nebenwirkungen
bull qualitative undoder quantitative Bewertung
bull chemische Stoffe dose-response-assessment
bull biologische oder physikalische Stoffe dose-response-
assessment wenn die Daten vorliegen
bull Daten aus wissenschaftlicher Forschung toxikologischen
epidemiologische Studien und Statistiken
Exposure assessment ndash Expositionsabschaumltzung
bull qualitative undoder quantitative Bewertung des
Ausmaszliges eines Erregers
bull gesamte aktuelle Exposition der Bevoumllkerung
bull basiert auf der Verknuumlpfung von Verzehrsdaten
bestimmter Lebensmittel mit dem Vorhandensein der
Substanz in den betroffenen Lebensmitteln
Prinzipien des Risk assessment
26042017
5
Prinzipien des Risk assessment
Risk characterisation ndash Risikocharakterisierung
Integration von hazard identification hazard characterization
and exposure assessment in einer Schaumltzung der
Nebenwirkungen inklusive der auftretenden Unsicherheiten
die in der Population auftreten koumlnnen
Plant Selection
Agriculture begins with the collection and planting of seeds from wild plants
Occurs in 8 locations throughout the world between 7000 -12000 years ago
Selections were made based on yield seed size and taste
7
Biotechnology and Agriculture development
Landraces Diversity
10
Refers to the particular kinds of old seed strains and varieties that are farmer-selected in areas where local subsistence agriculture has long prevailed Landraces are highly adapted to specific locales or groups
Definition modified by native and also immigrant farmers
The term is usually applied to varieties of corn squash and beans that were domesticated by native farmers
GREEN Revolution
13
Term coined by US Agency 1968) Movement to increase yields by using New crop cultivars Irrigation Fertilizers Pesticides Mechanization A planned international effort funded by Rockefeller Foundation Ford Foundation Many developing country governments Purposed to eliminated hunger by improving crop performance Norman Borlaug ( 1970 Nobel price)
26042017
6
T Malthus 1766- 1834Crisis in food production
12
Models for population growth and food security
Pessimistic or Alarmist Theory
Malthus - 19th century Coale amp Hoover (1958)
Paul Ehrlich (Population Bomb)
Meadows (Limits to Growth) ndash 1960s and 1970s
Focus on population policy amp fixed non-renewable resources
Optimistic Theory
Ester Boserup ndash 1960s ndash 70s (agric Intensification)
Julian Simon ndash 1970s - 80s (human capital)
Neutralist or Revisionist Theory
Pflanzenzuumlchtung
Breeding yield time for development
29
Klassische Zuumlchtungsmethoden
AuslesezuumlchtungSelektionszuumlchtungDie Auslesezuumlchtung faumlngt mit dem Anbau von Genotypengemischen (vorh genetische Linien auch Wildpflanzen) an Aus dem nach gemeinsamer Abbluumlte erzeugten Saatgut werden Pflanzen mit vorteilhaften Eigenschaften ausgewaumlhlt (Zuchtwahl Massenauslese) KombinationszuumlchtungDie Kombinationszuumlchtung ist eine Kreuzung verschiedener Genotypen (Linien) Es entsteht ein neuer Genotyp
HeterosiszuumlchtungIn der Heterosiszuumlchtung werden bei Fremdbefruchtern (Mais Roggenhellip) in mehrjaumlhriger Zuumlchtung aus heterozygoten Ausgangspflanzen nahezu homozygote Inzuchtlinien gezuumlchtet Kreuzt man zwei solche Linien tritt bei der F1 Generation oft eine auffallende Mehrleistung gegenuumlber der Elternformen auf Dies nennt man bdquoHeterosis-Effekt
HybridzuumlchtungDie Hybridzuumlchtung ist ein Beispiel fuumlr Heterosiszuumlchtung zur Erzielung einer hohen markt- oder betriebsgerechten pflanzlichen Produktion durch Bastardwuumlchsigkeit So werden bei der Hybridzuumlchtung geeignete gesondert gezuumlchtete Inzuchtlinien einmalig miteinander gekreuzt (Einfachhybride) [1] Die Nachkommen der ersten Generation (F1) einer solchen Kreuzung haben gegenuumlber der Elterngeneration ein uumlppigeres Wachstum (HeterosiseffektFuumlr den Landwirt bedeutet dies jedoch dass das Saatgut jedes Jahr wieder neu bezogen werden muss wenn er den Ertragsvorteil gegenuumlber Nicht-Hybriden weiterhin erhalten will da der Heterosiseffekt nur in der F1-Generation auftritt und danach wieder verloren geht
MutationszuumlchtungBei der Mutationszuumlchtung werden Samen Roumlntgen- oder Neutronenstrahlen Kaumllte- und Waumlrmeschocks oder anderen Mutagenen ausgesetzt[2] um neue Eigenschaften durch Mutation zu erzielen die einen positiven Effekt aufweisen Damit wird die Zuumlchtung neuer Sorten erheblich beschleunigt
26042017
7
Hybridzuumlchtung Heterosis Hybrid Heterosis effect
Introducing new traits in a plant family(Random) Mutation Breeding
67
IAEA
26042017
8
Breeding Irradiation
Irradiator at Institute of
Radiation Breeding Ibaraki-ken JAPAN (httpwwwirbaffrcgojp)
68
Mutation breeding
69
Tissue culture Clones
70
Somaclonal variation
Production of a new variety of japanese
butterbur using somaclonal variation(uppernew variety lowernative variety)
71
26042017
9
Tomoffel Breeding using transposons
72
Ein Transposon ist ein DNA-Abschnitt bestimmter Laumlnge im Genom der seine Position im Genom veraumlndern kann (Transposition) Man unterscheidet Transposons deren mobile Zwischenstufe von RNA gebildet wird (Retroelemente oder Klasse-I-Transposon) von denjenigen deren mobile Phase DNA ist (DNA-Transposon oder Klasse-II-Transposon)
Transposon tagging
The molecular isolation of transposable elements now permits the cloning of genes in which the element resides The major advantage of this system is that genes whose function is not known can be cloned
75
Molecular marker directed breeding
73
26042017
10
Bio-Technology
INTEGRATED Pest Management A modern Way of Agriculture
74
Cloning Definition
Cloning is the process of making an identicalcopy of something
In biology it collectively refers to processesused to
-- copies of DNA Fragments (molecular cloning)-- cells (cell cloning)-- organism
The term also covers when organisms such as bacteria insectsor plants reproduce asexually
DNA cloning
To clone a piece of DNA DNAis cut into fragments usingrestriction enzymes thatrecognize specific sequencesof bases in DNA Thefragments are pasted intovectors that have been cut bythe same restriction enzymeVectors (eg plasmids orviruses) are needed to transferand maintain DNA in a hostcell
Reproductive Cloning
Reproductive cloning is a technology used to generate an animal thathas the same nuclear DNA as another currently or previously existinganimal Dolly was created by reproductive cloning technology In aprocess called somatic cell nuclear transfer (SCNT) scientists transfergenetic material from the nucleus of a donor adult cell to an egg whosenucleus has been removed The reconstructed egg containing the DNAfrom a donor cell must be treated with chemicals or electric current inorder to stimulate cell division Once the cloned embryo reaches asuitable stage it is transferred to the uterus of a female host where itcontinues to develop until birth
26042017
11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
26042017
12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
3
CODEX CODEX
Definitionen
Hazard Eigenschaften eines Stoffes oder Mischung von
Stoffen die bei der Herstellung beim Gebrauch oder der
Entsorgung negative Auswirkungen auf den Organismus oder
die Umwelt haben koumlnnen
Risiko Risiko ist die Moumlglichkeit dass ein schaumldigendes
Ereignis unter bestimmten Bedingungen aufgrund der
Exposition chemischer oder physikalischer Stoffe auftritt oder
die zu erwartende Haumlufigkeit des Auftretens eines
schaumldigenden Ereignisses
Hazard qualitativer Begriff
Risiko quantitativer Begriff
bull Risikobewertung
bull Strukturierter Prozess
bull Ziel Charakterisierung der Natur und der
Wahrscheinlichkeit eines negativen Resultats
bull basiert auf wissenschaftlichen Erkenntnissen
bull transparent objektiv nachvollziehbar
Risk assessment
26042017
4
Risk assessment
bull Identifikation der Gefahren
bull Charakterisierung der Gefahren
bull Expositionsabschaumltzung
bull Charakterisierung der Risiken
Hazard identification ndash Gefahrenidentifizierung
bull Identifikation von bekannten oder unbekannten
Gesundheitsgefahren in Verbindung mit einer bestimmten
Substanz
bull biologische (Mikroorganismen wie zB Salmonellen
Listerien)
bull chemische (Pestizide Tierarzneimittel Schwermetalle
usw)
bull physikalische Gefahren (Fremdkoumlrper wie zB Steine
Glas
Prinzipien des Risk assessment
Prinzipien des Risk assessment
Hazard characterisation ndash Gefahrencharakterisierung
bull bestimmt Erreger und moumlgliche Nebenwirkungen
bull qualitative undoder quantitative Bewertung
bull chemische Stoffe dose-response-assessment
bull biologische oder physikalische Stoffe dose-response-
assessment wenn die Daten vorliegen
bull Daten aus wissenschaftlicher Forschung toxikologischen
epidemiologische Studien und Statistiken
Exposure assessment ndash Expositionsabschaumltzung
bull qualitative undoder quantitative Bewertung des
Ausmaszliges eines Erregers
bull gesamte aktuelle Exposition der Bevoumllkerung
bull basiert auf der Verknuumlpfung von Verzehrsdaten
bestimmter Lebensmittel mit dem Vorhandensein der
Substanz in den betroffenen Lebensmitteln
Prinzipien des Risk assessment
26042017
5
Prinzipien des Risk assessment
Risk characterisation ndash Risikocharakterisierung
Integration von hazard identification hazard characterization
and exposure assessment in einer Schaumltzung der
Nebenwirkungen inklusive der auftretenden Unsicherheiten
die in der Population auftreten koumlnnen
Plant Selection
Agriculture begins with the collection and planting of seeds from wild plants
Occurs in 8 locations throughout the world between 7000 -12000 years ago
Selections were made based on yield seed size and taste
7
Biotechnology and Agriculture development
Landraces Diversity
10
Refers to the particular kinds of old seed strains and varieties that are farmer-selected in areas where local subsistence agriculture has long prevailed Landraces are highly adapted to specific locales or groups
Definition modified by native and also immigrant farmers
The term is usually applied to varieties of corn squash and beans that were domesticated by native farmers
GREEN Revolution
13
Term coined by US Agency 1968) Movement to increase yields by using New crop cultivars Irrigation Fertilizers Pesticides Mechanization A planned international effort funded by Rockefeller Foundation Ford Foundation Many developing country governments Purposed to eliminated hunger by improving crop performance Norman Borlaug ( 1970 Nobel price)
26042017
6
T Malthus 1766- 1834Crisis in food production
12
Models for population growth and food security
Pessimistic or Alarmist Theory
Malthus - 19th century Coale amp Hoover (1958)
Paul Ehrlich (Population Bomb)
Meadows (Limits to Growth) ndash 1960s and 1970s
Focus on population policy amp fixed non-renewable resources
Optimistic Theory
Ester Boserup ndash 1960s ndash 70s (agric Intensification)
Julian Simon ndash 1970s - 80s (human capital)
Neutralist or Revisionist Theory
Pflanzenzuumlchtung
Breeding yield time for development
29
Klassische Zuumlchtungsmethoden
AuslesezuumlchtungSelektionszuumlchtungDie Auslesezuumlchtung faumlngt mit dem Anbau von Genotypengemischen (vorh genetische Linien auch Wildpflanzen) an Aus dem nach gemeinsamer Abbluumlte erzeugten Saatgut werden Pflanzen mit vorteilhaften Eigenschaften ausgewaumlhlt (Zuchtwahl Massenauslese) KombinationszuumlchtungDie Kombinationszuumlchtung ist eine Kreuzung verschiedener Genotypen (Linien) Es entsteht ein neuer Genotyp
HeterosiszuumlchtungIn der Heterosiszuumlchtung werden bei Fremdbefruchtern (Mais Roggenhellip) in mehrjaumlhriger Zuumlchtung aus heterozygoten Ausgangspflanzen nahezu homozygote Inzuchtlinien gezuumlchtet Kreuzt man zwei solche Linien tritt bei der F1 Generation oft eine auffallende Mehrleistung gegenuumlber der Elternformen auf Dies nennt man bdquoHeterosis-Effekt
HybridzuumlchtungDie Hybridzuumlchtung ist ein Beispiel fuumlr Heterosiszuumlchtung zur Erzielung einer hohen markt- oder betriebsgerechten pflanzlichen Produktion durch Bastardwuumlchsigkeit So werden bei der Hybridzuumlchtung geeignete gesondert gezuumlchtete Inzuchtlinien einmalig miteinander gekreuzt (Einfachhybride) [1] Die Nachkommen der ersten Generation (F1) einer solchen Kreuzung haben gegenuumlber der Elterngeneration ein uumlppigeres Wachstum (HeterosiseffektFuumlr den Landwirt bedeutet dies jedoch dass das Saatgut jedes Jahr wieder neu bezogen werden muss wenn er den Ertragsvorteil gegenuumlber Nicht-Hybriden weiterhin erhalten will da der Heterosiseffekt nur in der F1-Generation auftritt und danach wieder verloren geht
MutationszuumlchtungBei der Mutationszuumlchtung werden Samen Roumlntgen- oder Neutronenstrahlen Kaumllte- und Waumlrmeschocks oder anderen Mutagenen ausgesetzt[2] um neue Eigenschaften durch Mutation zu erzielen die einen positiven Effekt aufweisen Damit wird die Zuumlchtung neuer Sorten erheblich beschleunigt
26042017
7
Hybridzuumlchtung Heterosis Hybrid Heterosis effect
Introducing new traits in a plant family(Random) Mutation Breeding
67
IAEA
26042017
8
Breeding Irradiation
Irradiator at Institute of
Radiation Breeding Ibaraki-ken JAPAN (httpwwwirbaffrcgojp)
68
Mutation breeding
69
Tissue culture Clones
70
Somaclonal variation
Production of a new variety of japanese
butterbur using somaclonal variation(uppernew variety lowernative variety)
71
26042017
9
Tomoffel Breeding using transposons
72
Ein Transposon ist ein DNA-Abschnitt bestimmter Laumlnge im Genom der seine Position im Genom veraumlndern kann (Transposition) Man unterscheidet Transposons deren mobile Zwischenstufe von RNA gebildet wird (Retroelemente oder Klasse-I-Transposon) von denjenigen deren mobile Phase DNA ist (DNA-Transposon oder Klasse-II-Transposon)
Transposon tagging
The molecular isolation of transposable elements now permits the cloning of genes in which the element resides The major advantage of this system is that genes whose function is not known can be cloned
75
Molecular marker directed breeding
73
26042017
10
Bio-Technology
INTEGRATED Pest Management A modern Way of Agriculture
74
Cloning Definition
Cloning is the process of making an identicalcopy of something
In biology it collectively refers to processesused to
-- copies of DNA Fragments (molecular cloning)-- cells (cell cloning)-- organism
The term also covers when organisms such as bacteria insectsor plants reproduce asexually
DNA cloning
To clone a piece of DNA DNAis cut into fragments usingrestriction enzymes thatrecognize specific sequencesof bases in DNA Thefragments are pasted intovectors that have been cut bythe same restriction enzymeVectors (eg plasmids orviruses) are needed to transferand maintain DNA in a hostcell
Reproductive Cloning
Reproductive cloning is a technology used to generate an animal thathas the same nuclear DNA as another currently or previously existinganimal Dolly was created by reproductive cloning technology In aprocess called somatic cell nuclear transfer (SCNT) scientists transfergenetic material from the nucleus of a donor adult cell to an egg whosenucleus has been removed The reconstructed egg containing the DNAfrom a donor cell must be treated with chemicals or electric current inorder to stimulate cell division Once the cloned embryo reaches asuitable stage it is transferred to the uterus of a female host where itcontinues to develop until birth
26042017
11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
26042017
12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
4
Risk assessment
bull Identifikation der Gefahren
bull Charakterisierung der Gefahren
bull Expositionsabschaumltzung
bull Charakterisierung der Risiken
Hazard identification ndash Gefahrenidentifizierung
bull Identifikation von bekannten oder unbekannten
Gesundheitsgefahren in Verbindung mit einer bestimmten
Substanz
bull biologische (Mikroorganismen wie zB Salmonellen
Listerien)
bull chemische (Pestizide Tierarzneimittel Schwermetalle
usw)
bull physikalische Gefahren (Fremdkoumlrper wie zB Steine
Glas
Prinzipien des Risk assessment
Prinzipien des Risk assessment
Hazard characterisation ndash Gefahrencharakterisierung
bull bestimmt Erreger und moumlgliche Nebenwirkungen
bull qualitative undoder quantitative Bewertung
bull chemische Stoffe dose-response-assessment
bull biologische oder physikalische Stoffe dose-response-
assessment wenn die Daten vorliegen
bull Daten aus wissenschaftlicher Forschung toxikologischen
epidemiologische Studien und Statistiken
Exposure assessment ndash Expositionsabschaumltzung
bull qualitative undoder quantitative Bewertung des
Ausmaszliges eines Erregers
bull gesamte aktuelle Exposition der Bevoumllkerung
bull basiert auf der Verknuumlpfung von Verzehrsdaten
bestimmter Lebensmittel mit dem Vorhandensein der
Substanz in den betroffenen Lebensmitteln
Prinzipien des Risk assessment
26042017
5
Prinzipien des Risk assessment
Risk characterisation ndash Risikocharakterisierung
Integration von hazard identification hazard characterization
and exposure assessment in einer Schaumltzung der
Nebenwirkungen inklusive der auftretenden Unsicherheiten
die in der Population auftreten koumlnnen
Plant Selection
Agriculture begins with the collection and planting of seeds from wild plants
Occurs in 8 locations throughout the world between 7000 -12000 years ago
Selections were made based on yield seed size and taste
7
Biotechnology and Agriculture development
Landraces Diversity
10
Refers to the particular kinds of old seed strains and varieties that are farmer-selected in areas where local subsistence agriculture has long prevailed Landraces are highly adapted to specific locales or groups
Definition modified by native and also immigrant farmers
The term is usually applied to varieties of corn squash and beans that were domesticated by native farmers
GREEN Revolution
13
Term coined by US Agency 1968) Movement to increase yields by using New crop cultivars Irrigation Fertilizers Pesticides Mechanization A planned international effort funded by Rockefeller Foundation Ford Foundation Many developing country governments Purposed to eliminated hunger by improving crop performance Norman Borlaug ( 1970 Nobel price)
26042017
6
T Malthus 1766- 1834Crisis in food production
12
Models for population growth and food security
Pessimistic or Alarmist Theory
Malthus - 19th century Coale amp Hoover (1958)
Paul Ehrlich (Population Bomb)
Meadows (Limits to Growth) ndash 1960s and 1970s
Focus on population policy amp fixed non-renewable resources
Optimistic Theory
Ester Boserup ndash 1960s ndash 70s (agric Intensification)
Julian Simon ndash 1970s - 80s (human capital)
Neutralist or Revisionist Theory
Pflanzenzuumlchtung
Breeding yield time for development
29
Klassische Zuumlchtungsmethoden
AuslesezuumlchtungSelektionszuumlchtungDie Auslesezuumlchtung faumlngt mit dem Anbau von Genotypengemischen (vorh genetische Linien auch Wildpflanzen) an Aus dem nach gemeinsamer Abbluumlte erzeugten Saatgut werden Pflanzen mit vorteilhaften Eigenschaften ausgewaumlhlt (Zuchtwahl Massenauslese) KombinationszuumlchtungDie Kombinationszuumlchtung ist eine Kreuzung verschiedener Genotypen (Linien) Es entsteht ein neuer Genotyp
HeterosiszuumlchtungIn der Heterosiszuumlchtung werden bei Fremdbefruchtern (Mais Roggenhellip) in mehrjaumlhriger Zuumlchtung aus heterozygoten Ausgangspflanzen nahezu homozygote Inzuchtlinien gezuumlchtet Kreuzt man zwei solche Linien tritt bei der F1 Generation oft eine auffallende Mehrleistung gegenuumlber der Elternformen auf Dies nennt man bdquoHeterosis-Effekt
HybridzuumlchtungDie Hybridzuumlchtung ist ein Beispiel fuumlr Heterosiszuumlchtung zur Erzielung einer hohen markt- oder betriebsgerechten pflanzlichen Produktion durch Bastardwuumlchsigkeit So werden bei der Hybridzuumlchtung geeignete gesondert gezuumlchtete Inzuchtlinien einmalig miteinander gekreuzt (Einfachhybride) [1] Die Nachkommen der ersten Generation (F1) einer solchen Kreuzung haben gegenuumlber der Elterngeneration ein uumlppigeres Wachstum (HeterosiseffektFuumlr den Landwirt bedeutet dies jedoch dass das Saatgut jedes Jahr wieder neu bezogen werden muss wenn er den Ertragsvorteil gegenuumlber Nicht-Hybriden weiterhin erhalten will da der Heterosiseffekt nur in der F1-Generation auftritt und danach wieder verloren geht
MutationszuumlchtungBei der Mutationszuumlchtung werden Samen Roumlntgen- oder Neutronenstrahlen Kaumllte- und Waumlrmeschocks oder anderen Mutagenen ausgesetzt[2] um neue Eigenschaften durch Mutation zu erzielen die einen positiven Effekt aufweisen Damit wird die Zuumlchtung neuer Sorten erheblich beschleunigt
26042017
7
Hybridzuumlchtung Heterosis Hybrid Heterosis effect
Introducing new traits in a plant family(Random) Mutation Breeding
67
IAEA
26042017
8
Breeding Irradiation
Irradiator at Institute of
Radiation Breeding Ibaraki-ken JAPAN (httpwwwirbaffrcgojp)
68
Mutation breeding
69
Tissue culture Clones
70
Somaclonal variation
Production of a new variety of japanese
butterbur using somaclonal variation(uppernew variety lowernative variety)
71
26042017
9
Tomoffel Breeding using transposons
72
Ein Transposon ist ein DNA-Abschnitt bestimmter Laumlnge im Genom der seine Position im Genom veraumlndern kann (Transposition) Man unterscheidet Transposons deren mobile Zwischenstufe von RNA gebildet wird (Retroelemente oder Klasse-I-Transposon) von denjenigen deren mobile Phase DNA ist (DNA-Transposon oder Klasse-II-Transposon)
Transposon tagging
The molecular isolation of transposable elements now permits the cloning of genes in which the element resides The major advantage of this system is that genes whose function is not known can be cloned
75
Molecular marker directed breeding
73
26042017
10
Bio-Technology
INTEGRATED Pest Management A modern Way of Agriculture
74
Cloning Definition
Cloning is the process of making an identicalcopy of something
In biology it collectively refers to processesused to
-- copies of DNA Fragments (molecular cloning)-- cells (cell cloning)-- organism
The term also covers when organisms such as bacteria insectsor plants reproduce asexually
DNA cloning
To clone a piece of DNA DNAis cut into fragments usingrestriction enzymes thatrecognize specific sequencesof bases in DNA Thefragments are pasted intovectors that have been cut bythe same restriction enzymeVectors (eg plasmids orviruses) are needed to transferand maintain DNA in a hostcell
Reproductive Cloning
Reproductive cloning is a technology used to generate an animal thathas the same nuclear DNA as another currently or previously existinganimal Dolly was created by reproductive cloning technology In aprocess called somatic cell nuclear transfer (SCNT) scientists transfergenetic material from the nucleus of a donor adult cell to an egg whosenucleus has been removed The reconstructed egg containing the DNAfrom a donor cell must be treated with chemicals or electric current inorder to stimulate cell division Once the cloned embryo reaches asuitable stage it is transferred to the uterus of a female host where itcontinues to develop until birth
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11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
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GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
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Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
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Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
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17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
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CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
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20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
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Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
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22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
5
Prinzipien des Risk assessment
Risk characterisation ndash Risikocharakterisierung
Integration von hazard identification hazard characterization
and exposure assessment in einer Schaumltzung der
Nebenwirkungen inklusive der auftretenden Unsicherheiten
die in der Population auftreten koumlnnen
Plant Selection
Agriculture begins with the collection and planting of seeds from wild plants
Occurs in 8 locations throughout the world between 7000 -12000 years ago
Selections were made based on yield seed size and taste
7
Biotechnology and Agriculture development
Landraces Diversity
10
Refers to the particular kinds of old seed strains and varieties that are farmer-selected in areas where local subsistence agriculture has long prevailed Landraces are highly adapted to specific locales or groups
Definition modified by native and also immigrant farmers
The term is usually applied to varieties of corn squash and beans that were domesticated by native farmers
GREEN Revolution
13
Term coined by US Agency 1968) Movement to increase yields by using New crop cultivars Irrigation Fertilizers Pesticides Mechanization A planned international effort funded by Rockefeller Foundation Ford Foundation Many developing country governments Purposed to eliminated hunger by improving crop performance Norman Borlaug ( 1970 Nobel price)
26042017
6
T Malthus 1766- 1834Crisis in food production
12
Models for population growth and food security
Pessimistic or Alarmist Theory
Malthus - 19th century Coale amp Hoover (1958)
Paul Ehrlich (Population Bomb)
Meadows (Limits to Growth) ndash 1960s and 1970s
Focus on population policy amp fixed non-renewable resources
Optimistic Theory
Ester Boserup ndash 1960s ndash 70s (agric Intensification)
Julian Simon ndash 1970s - 80s (human capital)
Neutralist or Revisionist Theory
Pflanzenzuumlchtung
Breeding yield time for development
29
Klassische Zuumlchtungsmethoden
AuslesezuumlchtungSelektionszuumlchtungDie Auslesezuumlchtung faumlngt mit dem Anbau von Genotypengemischen (vorh genetische Linien auch Wildpflanzen) an Aus dem nach gemeinsamer Abbluumlte erzeugten Saatgut werden Pflanzen mit vorteilhaften Eigenschaften ausgewaumlhlt (Zuchtwahl Massenauslese) KombinationszuumlchtungDie Kombinationszuumlchtung ist eine Kreuzung verschiedener Genotypen (Linien) Es entsteht ein neuer Genotyp
HeterosiszuumlchtungIn der Heterosiszuumlchtung werden bei Fremdbefruchtern (Mais Roggenhellip) in mehrjaumlhriger Zuumlchtung aus heterozygoten Ausgangspflanzen nahezu homozygote Inzuchtlinien gezuumlchtet Kreuzt man zwei solche Linien tritt bei der F1 Generation oft eine auffallende Mehrleistung gegenuumlber der Elternformen auf Dies nennt man bdquoHeterosis-Effekt
HybridzuumlchtungDie Hybridzuumlchtung ist ein Beispiel fuumlr Heterosiszuumlchtung zur Erzielung einer hohen markt- oder betriebsgerechten pflanzlichen Produktion durch Bastardwuumlchsigkeit So werden bei der Hybridzuumlchtung geeignete gesondert gezuumlchtete Inzuchtlinien einmalig miteinander gekreuzt (Einfachhybride) [1] Die Nachkommen der ersten Generation (F1) einer solchen Kreuzung haben gegenuumlber der Elterngeneration ein uumlppigeres Wachstum (HeterosiseffektFuumlr den Landwirt bedeutet dies jedoch dass das Saatgut jedes Jahr wieder neu bezogen werden muss wenn er den Ertragsvorteil gegenuumlber Nicht-Hybriden weiterhin erhalten will da der Heterosiseffekt nur in der F1-Generation auftritt und danach wieder verloren geht
MutationszuumlchtungBei der Mutationszuumlchtung werden Samen Roumlntgen- oder Neutronenstrahlen Kaumllte- und Waumlrmeschocks oder anderen Mutagenen ausgesetzt[2] um neue Eigenschaften durch Mutation zu erzielen die einen positiven Effekt aufweisen Damit wird die Zuumlchtung neuer Sorten erheblich beschleunigt
26042017
7
Hybridzuumlchtung Heterosis Hybrid Heterosis effect
Introducing new traits in a plant family(Random) Mutation Breeding
67
IAEA
26042017
8
Breeding Irradiation
Irradiator at Institute of
Radiation Breeding Ibaraki-ken JAPAN (httpwwwirbaffrcgojp)
68
Mutation breeding
69
Tissue culture Clones
70
Somaclonal variation
Production of a new variety of japanese
butterbur using somaclonal variation(uppernew variety lowernative variety)
71
26042017
9
Tomoffel Breeding using transposons
72
Ein Transposon ist ein DNA-Abschnitt bestimmter Laumlnge im Genom der seine Position im Genom veraumlndern kann (Transposition) Man unterscheidet Transposons deren mobile Zwischenstufe von RNA gebildet wird (Retroelemente oder Klasse-I-Transposon) von denjenigen deren mobile Phase DNA ist (DNA-Transposon oder Klasse-II-Transposon)
Transposon tagging
The molecular isolation of transposable elements now permits the cloning of genes in which the element resides The major advantage of this system is that genes whose function is not known can be cloned
75
Molecular marker directed breeding
73
26042017
10
Bio-Technology
INTEGRATED Pest Management A modern Way of Agriculture
74
Cloning Definition
Cloning is the process of making an identicalcopy of something
In biology it collectively refers to processesused to
-- copies of DNA Fragments (molecular cloning)-- cells (cell cloning)-- organism
The term also covers when organisms such as bacteria insectsor plants reproduce asexually
DNA cloning
To clone a piece of DNA DNAis cut into fragments usingrestriction enzymes thatrecognize specific sequencesof bases in DNA Thefragments are pasted intovectors that have been cut bythe same restriction enzymeVectors (eg plasmids orviruses) are needed to transferand maintain DNA in a hostcell
Reproductive Cloning
Reproductive cloning is a technology used to generate an animal thathas the same nuclear DNA as another currently or previously existinganimal Dolly was created by reproductive cloning technology In aprocess called somatic cell nuclear transfer (SCNT) scientists transfergenetic material from the nucleus of a donor adult cell to an egg whosenucleus has been removed The reconstructed egg containing the DNAfrom a donor cell must be treated with chemicals or electric current inorder to stimulate cell division Once the cloned embryo reaches asuitable stage it is transferred to the uterus of a female host where itcontinues to develop until birth
26042017
11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
26042017
12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
6
T Malthus 1766- 1834Crisis in food production
12
Models for population growth and food security
Pessimistic or Alarmist Theory
Malthus - 19th century Coale amp Hoover (1958)
Paul Ehrlich (Population Bomb)
Meadows (Limits to Growth) ndash 1960s and 1970s
Focus on population policy amp fixed non-renewable resources
Optimistic Theory
Ester Boserup ndash 1960s ndash 70s (agric Intensification)
Julian Simon ndash 1970s - 80s (human capital)
Neutralist or Revisionist Theory
Pflanzenzuumlchtung
Breeding yield time for development
29
Klassische Zuumlchtungsmethoden
AuslesezuumlchtungSelektionszuumlchtungDie Auslesezuumlchtung faumlngt mit dem Anbau von Genotypengemischen (vorh genetische Linien auch Wildpflanzen) an Aus dem nach gemeinsamer Abbluumlte erzeugten Saatgut werden Pflanzen mit vorteilhaften Eigenschaften ausgewaumlhlt (Zuchtwahl Massenauslese) KombinationszuumlchtungDie Kombinationszuumlchtung ist eine Kreuzung verschiedener Genotypen (Linien) Es entsteht ein neuer Genotyp
HeterosiszuumlchtungIn der Heterosiszuumlchtung werden bei Fremdbefruchtern (Mais Roggenhellip) in mehrjaumlhriger Zuumlchtung aus heterozygoten Ausgangspflanzen nahezu homozygote Inzuchtlinien gezuumlchtet Kreuzt man zwei solche Linien tritt bei der F1 Generation oft eine auffallende Mehrleistung gegenuumlber der Elternformen auf Dies nennt man bdquoHeterosis-Effekt
HybridzuumlchtungDie Hybridzuumlchtung ist ein Beispiel fuumlr Heterosiszuumlchtung zur Erzielung einer hohen markt- oder betriebsgerechten pflanzlichen Produktion durch Bastardwuumlchsigkeit So werden bei der Hybridzuumlchtung geeignete gesondert gezuumlchtete Inzuchtlinien einmalig miteinander gekreuzt (Einfachhybride) [1] Die Nachkommen der ersten Generation (F1) einer solchen Kreuzung haben gegenuumlber der Elterngeneration ein uumlppigeres Wachstum (HeterosiseffektFuumlr den Landwirt bedeutet dies jedoch dass das Saatgut jedes Jahr wieder neu bezogen werden muss wenn er den Ertragsvorteil gegenuumlber Nicht-Hybriden weiterhin erhalten will da der Heterosiseffekt nur in der F1-Generation auftritt und danach wieder verloren geht
MutationszuumlchtungBei der Mutationszuumlchtung werden Samen Roumlntgen- oder Neutronenstrahlen Kaumllte- und Waumlrmeschocks oder anderen Mutagenen ausgesetzt[2] um neue Eigenschaften durch Mutation zu erzielen die einen positiven Effekt aufweisen Damit wird die Zuumlchtung neuer Sorten erheblich beschleunigt
26042017
7
Hybridzuumlchtung Heterosis Hybrid Heterosis effect
Introducing new traits in a plant family(Random) Mutation Breeding
67
IAEA
26042017
8
Breeding Irradiation
Irradiator at Institute of
Radiation Breeding Ibaraki-ken JAPAN (httpwwwirbaffrcgojp)
68
Mutation breeding
69
Tissue culture Clones
70
Somaclonal variation
Production of a new variety of japanese
butterbur using somaclonal variation(uppernew variety lowernative variety)
71
26042017
9
Tomoffel Breeding using transposons
72
Ein Transposon ist ein DNA-Abschnitt bestimmter Laumlnge im Genom der seine Position im Genom veraumlndern kann (Transposition) Man unterscheidet Transposons deren mobile Zwischenstufe von RNA gebildet wird (Retroelemente oder Klasse-I-Transposon) von denjenigen deren mobile Phase DNA ist (DNA-Transposon oder Klasse-II-Transposon)
Transposon tagging
The molecular isolation of transposable elements now permits the cloning of genes in which the element resides The major advantage of this system is that genes whose function is not known can be cloned
75
Molecular marker directed breeding
73
26042017
10
Bio-Technology
INTEGRATED Pest Management A modern Way of Agriculture
74
Cloning Definition
Cloning is the process of making an identicalcopy of something
In biology it collectively refers to processesused to
-- copies of DNA Fragments (molecular cloning)-- cells (cell cloning)-- organism
The term also covers when organisms such as bacteria insectsor plants reproduce asexually
DNA cloning
To clone a piece of DNA DNAis cut into fragments usingrestriction enzymes thatrecognize specific sequencesof bases in DNA Thefragments are pasted intovectors that have been cut bythe same restriction enzymeVectors (eg plasmids orviruses) are needed to transferand maintain DNA in a hostcell
Reproductive Cloning
Reproductive cloning is a technology used to generate an animal thathas the same nuclear DNA as another currently or previously existinganimal Dolly was created by reproductive cloning technology In aprocess called somatic cell nuclear transfer (SCNT) scientists transfergenetic material from the nucleus of a donor adult cell to an egg whosenucleus has been removed The reconstructed egg containing the DNAfrom a donor cell must be treated with chemicals or electric current inorder to stimulate cell division Once the cloned embryo reaches asuitable stage it is transferred to the uterus of a female host where itcontinues to develop until birth
26042017
11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
26042017
12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
7
Hybridzuumlchtung Heterosis Hybrid Heterosis effect
Introducing new traits in a plant family(Random) Mutation Breeding
67
IAEA
26042017
8
Breeding Irradiation
Irradiator at Institute of
Radiation Breeding Ibaraki-ken JAPAN (httpwwwirbaffrcgojp)
68
Mutation breeding
69
Tissue culture Clones
70
Somaclonal variation
Production of a new variety of japanese
butterbur using somaclonal variation(uppernew variety lowernative variety)
71
26042017
9
Tomoffel Breeding using transposons
72
Ein Transposon ist ein DNA-Abschnitt bestimmter Laumlnge im Genom der seine Position im Genom veraumlndern kann (Transposition) Man unterscheidet Transposons deren mobile Zwischenstufe von RNA gebildet wird (Retroelemente oder Klasse-I-Transposon) von denjenigen deren mobile Phase DNA ist (DNA-Transposon oder Klasse-II-Transposon)
Transposon tagging
The molecular isolation of transposable elements now permits the cloning of genes in which the element resides The major advantage of this system is that genes whose function is not known can be cloned
75
Molecular marker directed breeding
73
26042017
10
Bio-Technology
INTEGRATED Pest Management A modern Way of Agriculture
74
Cloning Definition
Cloning is the process of making an identicalcopy of something
In biology it collectively refers to processesused to
-- copies of DNA Fragments (molecular cloning)-- cells (cell cloning)-- organism
The term also covers when organisms such as bacteria insectsor plants reproduce asexually
DNA cloning
To clone a piece of DNA DNAis cut into fragments usingrestriction enzymes thatrecognize specific sequencesof bases in DNA Thefragments are pasted intovectors that have been cut bythe same restriction enzymeVectors (eg plasmids orviruses) are needed to transferand maintain DNA in a hostcell
Reproductive Cloning
Reproductive cloning is a technology used to generate an animal thathas the same nuclear DNA as another currently or previously existinganimal Dolly was created by reproductive cloning technology In aprocess called somatic cell nuclear transfer (SCNT) scientists transfergenetic material from the nucleus of a donor adult cell to an egg whosenucleus has been removed The reconstructed egg containing the DNAfrom a donor cell must be treated with chemicals or electric current inorder to stimulate cell division Once the cloned embryo reaches asuitable stage it is transferred to the uterus of a female host where itcontinues to develop until birth
26042017
11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
26042017
12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
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Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
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Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
8
Breeding Irradiation
Irradiator at Institute of
Radiation Breeding Ibaraki-ken JAPAN (httpwwwirbaffrcgojp)
68
Mutation breeding
69
Tissue culture Clones
70
Somaclonal variation
Production of a new variety of japanese
butterbur using somaclonal variation(uppernew variety lowernative variety)
71
26042017
9
Tomoffel Breeding using transposons
72
Ein Transposon ist ein DNA-Abschnitt bestimmter Laumlnge im Genom der seine Position im Genom veraumlndern kann (Transposition) Man unterscheidet Transposons deren mobile Zwischenstufe von RNA gebildet wird (Retroelemente oder Klasse-I-Transposon) von denjenigen deren mobile Phase DNA ist (DNA-Transposon oder Klasse-II-Transposon)
Transposon tagging
The molecular isolation of transposable elements now permits the cloning of genes in which the element resides The major advantage of this system is that genes whose function is not known can be cloned
75
Molecular marker directed breeding
73
26042017
10
Bio-Technology
INTEGRATED Pest Management A modern Way of Agriculture
74
Cloning Definition
Cloning is the process of making an identicalcopy of something
In biology it collectively refers to processesused to
-- copies of DNA Fragments (molecular cloning)-- cells (cell cloning)-- organism
The term also covers when organisms such as bacteria insectsor plants reproduce asexually
DNA cloning
To clone a piece of DNA DNAis cut into fragments usingrestriction enzymes thatrecognize specific sequencesof bases in DNA Thefragments are pasted intovectors that have been cut bythe same restriction enzymeVectors (eg plasmids orviruses) are needed to transferand maintain DNA in a hostcell
Reproductive Cloning
Reproductive cloning is a technology used to generate an animal thathas the same nuclear DNA as another currently or previously existinganimal Dolly was created by reproductive cloning technology In aprocess called somatic cell nuclear transfer (SCNT) scientists transfergenetic material from the nucleus of a donor adult cell to an egg whosenucleus has been removed The reconstructed egg containing the DNAfrom a donor cell must be treated with chemicals or electric current inorder to stimulate cell division Once the cloned embryo reaches asuitable stage it is transferred to the uterus of a female host where itcontinues to develop until birth
26042017
11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
26042017
12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
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44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
9
Tomoffel Breeding using transposons
72
Ein Transposon ist ein DNA-Abschnitt bestimmter Laumlnge im Genom der seine Position im Genom veraumlndern kann (Transposition) Man unterscheidet Transposons deren mobile Zwischenstufe von RNA gebildet wird (Retroelemente oder Klasse-I-Transposon) von denjenigen deren mobile Phase DNA ist (DNA-Transposon oder Klasse-II-Transposon)
Transposon tagging
The molecular isolation of transposable elements now permits the cloning of genes in which the element resides The major advantage of this system is that genes whose function is not known can be cloned
75
Molecular marker directed breeding
73
26042017
10
Bio-Technology
INTEGRATED Pest Management A modern Way of Agriculture
74
Cloning Definition
Cloning is the process of making an identicalcopy of something
In biology it collectively refers to processesused to
-- copies of DNA Fragments (molecular cloning)-- cells (cell cloning)-- organism
The term also covers when organisms such as bacteria insectsor plants reproduce asexually
DNA cloning
To clone a piece of DNA DNAis cut into fragments usingrestriction enzymes thatrecognize specific sequencesof bases in DNA Thefragments are pasted intovectors that have been cut bythe same restriction enzymeVectors (eg plasmids orviruses) are needed to transferand maintain DNA in a hostcell
Reproductive Cloning
Reproductive cloning is a technology used to generate an animal thathas the same nuclear DNA as another currently or previously existinganimal Dolly was created by reproductive cloning technology In aprocess called somatic cell nuclear transfer (SCNT) scientists transfergenetic material from the nucleus of a donor adult cell to an egg whosenucleus has been removed The reconstructed egg containing the DNAfrom a donor cell must be treated with chemicals or electric current inorder to stimulate cell division Once the cloned embryo reaches asuitable stage it is transferred to the uterus of a female host where itcontinues to develop until birth
26042017
11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
26042017
12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
10
Bio-Technology
INTEGRATED Pest Management A modern Way of Agriculture
74
Cloning Definition
Cloning is the process of making an identicalcopy of something
In biology it collectively refers to processesused to
-- copies of DNA Fragments (molecular cloning)-- cells (cell cloning)-- organism
The term also covers when organisms such as bacteria insectsor plants reproduce asexually
DNA cloning
To clone a piece of DNA DNAis cut into fragments usingrestriction enzymes thatrecognize specific sequencesof bases in DNA Thefragments are pasted intovectors that have been cut bythe same restriction enzymeVectors (eg plasmids orviruses) are needed to transferand maintain DNA in a hostcell
Reproductive Cloning
Reproductive cloning is a technology used to generate an animal thathas the same nuclear DNA as another currently or previously existinganimal Dolly was created by reproductive cloning technology In aprocess called somatic cell nuclear transfer (SCNT) scientists transfergenetic material from the nucleus of a donor adult cell to an egg whosenucleus has been removed The reconstructed egg containing the DNAfrom a donor cell must be treated with chemicals or electric current inorder to stimulate cell division Once the cloned embryo reaches asuitable stage it is transferred to the uterus of a female host where itcontinues to develop until birth
26042017
11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
26042017
12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
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Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
11
Reproductive Cloning
168
Therapeutic CloningTherapeutic cloning also called embryo cloning is the production ofhuman embryos for use in research The goal of this process is not tocreate cloned human beings but rather to harvest stem cells that can beused to study human development and to treat disease Stem cells areextracted from the egg after it has divided for 5 daysThe extraction process destroys the embryo which raises a variety ofethical concerns Many researchers hope that one day stem cells can beused to serve as replacement cells to treat heart disease Alzheimerscancer and other diseases
Horticultural cloning
All plants which are originated from vegetativ reproductionsare clonesThey have been derived from a single individual multiplied bysome process other than sexual reproductionExamples are bananas grapes and potatoes
26042017
12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
12
GM plants Tranferring traits in ways which are not used in nature GMOs
79
Agrobact tumefaciens
123
T DNA
124
Homolog recombination
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
13
Antibiotic resistance marker gene
httpwwwgmo-compassorg
Gene gun
125
Methods overview
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
14
Herbicide tolerance glyphosate
130 131
Herbicide Resistance more or less herbicide depending on local agricultural background
Roundup Ready Soy Corn
Canola
Allows post-emergence herbicide spraying
Increases yield
Facilitates no-till farming
89 US Soy crop (2006)
144
Old and new Problems Resistance Herbicide Resistant Weeds
Evolve
Number of Evolved Glyphosate-
Resistant Weed Species
132
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
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Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
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Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
15
Herbizide resistance gene transfer
133
Gene flow multiresistant Rape
Insect resistance BT maize
134
BT resistance B thuringiensis proteins
138
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
16
Roundup ready Monsanto
137
Maiszuumlnsler wirtschaftlich bedeutendster Maisschaumldling
Es gibt mehrere Strategien zur Bekaumlmpfung des Maiszuumlnslers
bull mechanisch durch Zerkleinern und Unterpfluumlgen der auf dem Feld verbliebenen Pflanzenreste
bull chemisch durch Einsatz von Insektiziden
bull biologisch mit Hilfe von Trichogramma (Schlupfwespen)
bull BT Toxin Praumlparate
bull gentechnisch vermittelte Insektenresistenz besitzt (Bt-Mais)
135
Bt Corn
Natural insecticide from Bacillus thuringiensis
Non-toxic to humans
Target insect corn borer
Potential to
ndash reduce insecticide use
ndash reduce mycotoxins
40 US Corn crop Bt (2006)
142
Bt Concerns
Bt pollen harms non-target species
Bt crops select for resistant insects
Bt pollen can drift to organic fields
Food system failed to keep BT Starlink
corn out of human food products
143
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
17
140
Insect Resistant Cotton Disease Resistance viruses
Cantaloupes
Cucumbers
Corn
Rice
Papaya
Potatoes
Soybeans
Squash
Tomatoes
Wheat
Genetically engineered papaya resistant
papaya ringspot virus
146
(Devlin et al 1994)
Growth-enhanced fish
Auto-transgenic mud
loach β-actin promoter
linked to GH gene
157
Salmon Growth hormone expressed in cold waters amp unlinked from seasonal temp
GM Salmon
Kellner AnnaStoll Christiane
bull Probleme der Lachsindustrie
bull gv Lachs von Aqua Bounty
bull Produktionssteigerung uumlber Ernaumlhrung Krankheitsresistenz
bull Gefahr fuumlr die Wildlachspopulationen
bull Abhaumlngigkeit des Fischfutters
bull Umweltverschmutzung durch Lachszucht
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
18
bull Atlantischer Lachs von Aqua Bounty
bull Wachstumshormon-Gen des Chinook Lachs
bull Frostschutz-Protein-Gen
bull bessere Entwicklung in kalten kanadischen Gewaumlssern
bull Wachstum uumlber das ganze Jahr
bull normales Gewicht in der Haumllfte der Zeit erreicht
gv Lachs
BELFOND-CURIEUX OL et al Factors to consider before production and commercialization of aquatic genetically modified organisms the case of transgenic salmon Environmental Science amp Policy 12 170-189 2009
Golden Rice
147
Goldener Reis
Unter Goldenem Reis (engl Golden Rice) versteht man eine gentechnisch veraumlnderte Reissorte Es wurden zwei artfremde Gene und damit ein mehrschrittiger Syntheseweg in das Genom eingefuumlgt Das Phytoensynthase-Gen (psy) stammt von der Osterglocke(Narcissus pseudonarcissus) und das Carotindesaturase-Gen (crtI) von einem Bakterium Namens Erwinia uredovora (neuer Name Pantoea ananatis)
Dank dieser zwei Gene kommt es zur Bildung von Beta-Carotin (Provitamin A) im Endosperm der Reiskoumlrner die deshalb (gold-)gelb orange gefaumlrbt sind Das Provitamin wird dann im Koumlrper zu Vitamin A (Retinol) umgewandelt
GMO tobacco expression of human proteins in plants GMOs in development
CLAIMED BREEDING OBJECTIVES
152
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
19
CLAIMED BREEDING OBJECTIVES
153
09122008
Claimed breeding objectives
154
BREEDING OBJECTIVES
155
Breeding objectives
156
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
20
GMO TreesGM FLowers
To considerType of modification Molecul
sequenceEpigenetic Tox
directToxindirect
Environment
Agric-ulturalpractice
Classic breeding
Cross breeding
Random mutation
Cell culture transposons
Gene technology( bacteria plants animals vaccineshellip)
Cloning animals
26042017
21
Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
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Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
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De Facto Praxis Post
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18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
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Sicherheitsbeurteilung KonzeptRisk assessment
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Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
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Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
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Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
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Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
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Kritik EFSA zb Danacol
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LM aus nicht traditionellen Rohstoffen
Zb Lycopin
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LM pflanzliche Sekundaumlrstoffe
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LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
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Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
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Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
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Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
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The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
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Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
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Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
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Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
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New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
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60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
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62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
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63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
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65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
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Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
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Safety Random integration
Insertional mutagenesis
Promoter
1 Interrupt coding region and inactivate gene
Vector
2 Insert next to gene and activate its expression inappropriately
Vector
161
Molecular characterisationRR Soya
Detection of unintended effects in vitro in vivo
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22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
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Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
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CRISPR-Cas9 CRISPR-Cas9 applications
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25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
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Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
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Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
22
Toxicology Asessment Difficulties Animal Feeding Studies
Whole Foods
Small doses to be fed (bulk satiety)
Nutritional imbalance of the diet
Many confounding factors
Small safety margins if any
Insufficient sensitivity for specific endpoints
GMO tests PCR primers areas array
New Objectives Conventionalnew methods
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
23
Nucleases bdquoNaturalldquo editing of DNA
Site directed Insertion
1Site-directed nucleases andashc DNA nucleases bind to and cut DNA at specific locations Each nuclease comprises a DNA-cutting domain (depicted in blue) and a DNA-targeting domain Zinc-Finger Nucleases (ZFN) (a) and Transcription Activator-Like Effector Nucleases (TALENs) (b) possess protein-based DNA recognition domains (depicted by yellow and orange ovals) Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) nucleases (c) rely on single-guide RNAs (sgRNAs) to locate the target DNA The DNA recognition domain of all three nucleases can be engineered to target predetermined sites in the genome for the purposes of genome editing
Cas-Proteine koumlnnen als Ribonukleoproteine bestimmte RNA-Sequenzen binden Die Endonuklease Cas9 kann eine bestimmte RNA-Sequenz (crRNA repeat Sequenz GUUUUAGAGCU(AG)UG(CU)UGUUUUG) binden und in der unmittelbaren Umgebung DNA schneiden Diese crRNA repeat-Sequenz bildet eine RNA-Sekundaumlrstruktur und wird dann von Cas9 gebunden wodurch eine Aumlnderung der Proteinfaltung von Cas9 erfolgt und die Ziel-DNA von der RNA gebunden wirdWeiterhin ist das Vorhandensein von einem PAM-Motiv (englisch protospacer adjacent motif sbquoAngrenzendes Motiv an den Protospacerlsquo) mit der Sequenz NGG in der Ziel-DNA fuumlr eine Aktivierung von Cas9 notwendig Der Schnitt der DNA erfolgt drei Nukleotide vor dem PAM An der crRNA repeat-Sequenz befindet sich anschlieszligend eine an die Ziel-DNA bindende Sequenz (crRNA spacer) beide Sequenzen werden zusammen als crRNA bezeichnet Als zweiter Teil der crRNA dient die crRNA spacer-Sequenz in der Funktion eines variablen Adapters welche komplementaumlr zur Ziel-DNA ist und an die Ziel-DNA bindet Weiterhin ist noch eine zur DNA-Sequenz analoge RNA (tracrRNA von engl trans-acting CRISPR RNA) notwendig Dadurch wird die DNA gebunden und von der Endonukleasefunktion nahe der Bindungsstelle geschnitten Die DNA-Reparatur des erzeugten Doppelstrangbruchs erfolgt durch homology-directed repair (HDR) oder durch non-homologous end joining (NHEJ)
Anpassung an die ZielsequenzWird an eine crRNA repeat-Sequenz anstatt der natuumlrlich vorkommenden crRNA spacer-Sequenz eine andere zu einer DNA-Zielsequenz komplementaumlre RNA-Sequenz angefuumlgt und diese crRNA zu einer tracrRNA hinzugegeben schneidet Cas9 die DNA nahe der geaumlnderten Zielsequenz Die an die Ziel-DNA bindende Sequenz besteht aus 20 Nukleotiden von denen vor allem die 12 an das PAM angrenzendenNukleotide fuumlr die Bindungsspezifitaumlt entscheidend sind Die beiden RNA-Straumlnge der crRNA und der tracrRNA koumlnnen auch in einem einzelnen teilweise selbsthybridisierenden RNA-Strang untergebracht werden (sgRNA sbquosingle guide RNAlsquo) Durch das Cas9 mit den entsprechenden RNA-Sequenzen kann sequenzspezifisch doppelstraumlngige teilweise komplementaumlre DNA geschnitten werden wodurch gezielte Deletionen erzeugt werden koumlnnen Durch Transformation oder Transfektion von einem Vektor koumlnnen Lebewesen mit dem CRISPRCas-System ergaumlnzt werden die es natuumlrlicherweise nicht besitzen z B manche Bakterienstaumlmme Maumluse[und Menschen Fuumlr ein Genome Editing in der Keimbahn werden als Methoden zur Einschleusung des CRISPRCas9 die Elektroporation und die Mikroinjektion eingesetzt Die gleichzeitige Aumlnderung mehrerer DNA-Zielsequenzen wird als Multiplex Genome Editing bezeichnet
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
24
CRISPR-Cas9 CRISPR-Cas9 applications
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
25
Food production and conservation of Nature What is NATURE
ldquoNature to be commanded must be obeyedrdquo
Francis Bacon 1561 ndash 1626
Rise of natural science and nature
Jean-Jacques Rousseau1712-1778
Rousseau postulierte einen Menschen der im Naturzustand den Einklang mit der Natur sucht
Return to eden
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
26
Handle so daszlig die Wirkungen deiner Handlungen vertraumlglich sind mit der Permanenz echten menschlichen Lebens auf Erden
Property and responsibility The problem of land use transformation and Conservation
Carolyn Merchant
Conservation historyUniv of Berkley
Landuse and property
conservation expolitation
use property
Science 13 December 1968
Vol 162 no 3859 pp 1243 ndash 1248
Articles
The Tragedy of the Commons
Garrett Hardin
professor of biology University of California Santa Barbara
When a resource is held in common with many people having ownership and access to it Hardin reasoned a self-interested rational actor will decide to increase his or her exploitation of the resource since he or she receives the full benefit of the increase but the costs are spread among all users
Nature and property
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
27
Industrial and Corporate ChangePp 131-159
OSTROM E copy 1995 Oxford University Press
research-article
Self-organization and Social Capital ( building public goods )
ELINOR OSTROM
(Workshop in Political Theory and Policy Analysis Indiana University Bloomington IN 47408ndash3895 USA)
Nature and property Public goods ConservationThe problem of Diversity
Diversity sustainability and equal access to natural ressources UN sustainability Agenda 21
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
28
Millennium Ecosystem Assessment MA MA Framework
Direct Drivers
Indirect Drivers
EcosystemServices
Human Well-being
Direct Drivers of Change Changes in land use Species introduction or removal Technology adaptation and use External inputs (eg irrigation) Resource consumption Climate change Natural physical and biological
drivers (eg volcanoes)
Indirect Drivers of Change Demographic Economic (globalization trade
market and policy framework) Sociopolitical (governance and
institutional framework) Science and Technology Cultural and Religious
Human Well-being and Poverty Reduction
Basic material for a good life Health Good Social Relations Security Freedom of choice and action
Umwelt Sicherheit LMOs Clearing House
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
29
Biological diversity Cartagena Protokoll Trade WTO SPS
WTO trade TRIPS Trade Consequences
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
30
Regelungen Novel food 1782002 Basis VO
1782002 1782002
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
31
EU Regulatory framework on GMOs
DG Health and Consumer Protection
European Commission
Overview
EU legal framework
Scope of the legal acts and their interaction
The authorisation procedure
State of play concerning new authorisations
The so-called ldquoexisting productsrdquo
Labelling rules and thresholds
Conclusions
Marco Valletta 122
EU legislative framework in the 90s
Directive 90220EC
On the deliberate release of GMOs
first GM products approved maize soy oilseed r
Regulation (EC) N 25897 on Novel Foods
Notification of GM food and food ingredients
7 oilseed rape 4 maize oil from 2 cottonseeds
Marco Valletta 123
18 April 2004 ndash New legislative framework
Directive 200118 on the deliberate
release of GMOs into the environment
Regulation (EC) No 18292003
on GM food and feed
Regulation (EC) No 18302003
on traceability and labelling of GMOs
Marco Valletta 124
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
32
Directive 200118EC
Directive 200118EC on the deliberate release into the environment of GMOs Clear definition of GMO and relative techniq
Scope product containing GMOs or consisting of such organisms
The experimental release of GMOs into the environment (for example field trials)
The placing on the market of GMOs ( for ex cultivation importation or transformation)
Marco Valletta 125
Scope of Directive 200118 and Regulation 18292003
Directive 200118
ldquolivingrdquo GMOs
Marco Valletta 126
Reg 18292003
Foodfeed consisting containing
or produced from a GMO
Interaction between Directive 200118 and Regulation 18292003
Marco Valletta 127
GMOs not for
food feed
use ie GM
carnation
Foodfeed
consisting
of or
containing a
GMo
Foodfeed
produced
from a
GMO
One door one key principle
For products containingconsisting of GMOs
EITHER one single application under Reg 18292003 covering both of foodfeed use and the deliberate release of GMOs into the environment - in accordance with the criteria of Dir 200118
OR the application mdash or part of the application mdash can be split and submitted separately under Dir 200118 and Reg 18292003
GMOs likely to be used as food and feed can only be authorised for both uses after Starlink case
Marco Valletta 128
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
33
New legislative framework
Principles Centralised and transparent authorisation
procedure with a clear time frame
New rules on traceability and labelling
Applies on newly authorised and existing products
Clarifies what is currently on the market
Marco Valletta 129
The authorisation procedure (1)
General overview
Risk assessment European Food Safety Authority
Risk management European Commission through a regulatory committee procedure
Marco Valletta 130
The authorisation procedure (2)
First step - Application Submitted to the competent authority of a MS
The application dossier has to include
definition of the scope
safety dossier with the indication of confidential parts
monitoring plan
proposal of a detection method
Receipt in 14 days and inform EFSA
Marco Valletta 131
The authorisation procedure (3)
EFSA ndash Risk assessment GMO Panel ndash independent scientists
Both envir risk and human and animal health
Timeframe 6 months unless further information needed
Guidance documents httpwwwefsaeuint
Marco Valletta 132
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
34
The authorisation procedure (4)
Commission role ndash Risk management
Draft decision grantingrefusing authoris (3 months)
Justification if diverging from EFSA opinion
Proposal to be approved by a qualified majority in the SCOFCAH (Member States representatives)
IF No QM Council of Ministers
IF Council no action or no QM Commission adopts the decision (3 months)
Marco Valletta 133
The authorisation procedure (5)
AuthorisationGranted for 10 years
Renewable for 10-year periods
Subject to a post-market monitoring
Authorised products shall be entered in the public register of GM food and feed
Marco Valletta 134
State of play of new applications
14 applications received since full applicability of Regulation
GM food and feed uses import and processing no cultivation
Most of them maize (8) but also 3 cotton 1 rice 1 sugar beet and 1 potato variety
Marco Valletta 135 Marco Valletta 136
Product Applicant Status Current status clock
NK603 x MON810 Z Mays Monsanto Under completeness check
1507 Z Mays (only food)Pioneer Hi-Bred Mycogen Seeds
Final opinion adopted 03032005
MON863 x MON810 Z Mays Monsanto Valid applicationClock stopped on
09022005 (JRC)
LLRICE62Bayer CropScience
Valid applicationClock stopped on 09022005 (JRC)
21032005 (EFSA)
1507 x NK603 Z Mays Pioneer Hi-Bred Mycogen Seeds Valid application
MON863 x NK603 ZMaysMonsanto Valid application Clock stopped on 09022005 (JRC)
MON863 x MON810 x NK603Z
MaysMonsanto Valid application Clock stopped on 09022005 (JRC)
H7-1 Roundup Ready Sugar Beet KWS SAAT AG Monsanto Valid application
MON 531 x MON 1445 Cotton Monsanto Under completeness check
MON 15985 and MON 15985 x MON
1445 CottonMonsanto Under completeness check
MIR604 maize Syngenta Seeds Under completeness check
590122 Z Mays Pioneer Hi-Bred Mycogen Seeds Under completeness check
LLCotton25 Bayer CropScience Under completeness check
Amylopectin Potato Event EH92-
527-1BASF Plant Science Under completeness check
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
35
1507 GM maize ndash 1st product under the new framework
EFSA opinion on 3 of March 2005
Commission put authorisation proposal to vote after three months (03062005)
No QM in the SCOFCAH to the Council
Marco Valletta 137
1507 GM maize ndash the interaction between different legal actsAuthorisation as food under Regulation (EC) No 18292003 on GM
food and feed
Authorisation for import and processing under Directive 200118 ndashindicative vote on the 7 of March resulted in no QM
Authorisation for cultivation under Directive 200118
Marco Valletta 138
Categories of GM food and feed on the EU Market1 Newly authorised products under Reg (EC) No 18292003
2 Newly authorised products under Novel Food Regulation
3 Existing products that were already on the market on the 18 April 2004
Marco Valletta 139
Newly authorised products under Novel Food Regulation
Upgraded to the standards of Regulation 18292003 on GM food and feed
Bt11 and NK 603 maize authorised in 2004
GA 21 and MON 863 maize in the pipeline for 2005
Marco Valletta 140
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
36
Existing products Notification until 18 October 2004
Food and feed that fall into the scope of the Regulation and are on the market needed to be notified to the Commission
26 existing products were notified
Existing products are subject to the requirements of the new legislation Data package
Labelling and traceability requirements
Validation of detection method
Marco Valletta 141
Notified food products
GMOs authorised under Directive 90220
GM food and ingredients notified under the Novel Food Regulation
GM foodfeed that were already on the market and were not subject to a specific authorisation (for ex food additives produced from GMOs)
Marco Valletta 142
Notified products Examination until 18 April 2005Commission examined the notified products
Notifying companies requested to submit further information if necessary
Validation of detection methods to be completed
Marco Valletta 143
On 18 April 2005 ndash Entry into Register of GM food and feedAll the 26 notifications accepted entry into Register of GM food and feed (12
maize 6 oilseed rape 5 cotton 1 soybean biomass yeast cream)
httpeuropaeuintcommfoodfoodbiotechnologyauthorisationcommun_register_enhtm
Can remain on the market 3-9y then renewal
Some products were not notified ndash measures need to be taken to withdraw these from the market 3 products notified under Novel Food Regulation Possibly more
Marco Valletta 144
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
37
Labelling rules
GM products have to be labelled
According to Reg (EC) No 18302003 ldquoThis product contains GMOsrdquo or
ldquoThis product contains GM [name of the organism]rdquo
Pre-packaged on a label
Non pre-packaged on the display or in connection with the product
Marco Valletta 145
Labelling rules
According to Reg (EC) No 18292003 Compulsory GM labelling for food and feed indicating
- ldquogenetically modifiedrdquo
- ldquocontainsproduced from GM[name of the organism]rdquo
Labelling requirements apply regardless of the presence of modified DNA or proteins highly refined products and compound feed included
Not for products obtained from animals fed with GM feed or treated with GM medicines
Marco Valletta 146
Thresholds
Labelling and traceability requirements do NOT apply in case of adventitious or technically unavoidable presence IF
Traces of an authorised GMOs below the limit of 09
Operators have to prove that they have taken adequate measures to avoid the presence
Marco Valletta 147
Thresholds
Adventitious presence (burden of proof to the operators) of an unauthorised GMO
Positive assessment by an EU Scientific Committee is necessary
The threshold is fixed at 05
Below labelling and traceability not enforced
Above prohibition to put the product on the market
Marco Valletta 148
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
38
Are there labelled products on the market
Recent discussion in a WG of national experts
November 2004 77 GM labelled products on the markets of 10 EU countries (mostly in France Germany the Netherlands and Czech and Slovak Republics)
Strong resistance from the consumersrsquo side
Marco Valletta 149
Kennzeichnung
Fleisch Milch Eiervon Tieren die mit gv-Futtermitteln gefuumlttert
wurdenSind weiterhin nicht
kennzeichnungspflichtigO in tierischen Lebensmitteln
sind gentechnischeVeraumlnderungen aus
Futtermitteln nicht mehrnachweisbar
Implementation of the new legal framework
The framework is being successfully implemented
Major challenges
Missing data for safety assessment or validation of detection method EFSA ldquoclockrdquo not started or stopped Lacking support of Member States to the authorisation process final decision
is left to Commission
Report on implementation is due by November 2005 questionnaires to MS and stakeholders
Room for amendments
Marco Valletta 151
Summary
The new regulatory framework is implemented
A transparent and timely authorisation procedure based on sound scientific assessment is in force
The authorisation process has gained momentum
GM foods and feed are already on the EU market although still the object of public resistance
GM products have to be labelled according to the EU legislation
Marco Valletta 152
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
39
Conclusion
In the meeting of 22 March 2005 the Eur Comm engaged itself to the respect and full implementation of the described legal framework
The respect of the EU rules (esp traceability and labelling) by our trading partners is essential to win consumersrsquo confidence
Marco Valletta 153
More info
httpeuropaeuintcommfoodfood
biotechnologyindex_dehtm
Marco Valletta 154
Novel Foods definitions Categorisaton Novel foods
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
40
Ausnahmen Post 25897
Verordnung (EG) Nr 18292003 uumlberGV Lebensmittel und Futtermittel
Post 25897
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
41
De Facto Praxis Post
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
42
18302003 Ruumlckverfolgbarkeit
Ruumlckverfolgbarkeit Grenzen genetische Stabilitaumlt gene stacking
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
43
Sicherheitsbeurteilung KonzeptRisk assessment
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
44
Risikobewertung No Observed Adverse Effect Level
ToxRisiko Extrapolation ADI nach WHO
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
45
Toxikologie Tox Hazard
Geno toxizitaumlt Risko Nutzen
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
46
Risiko Nutzen Analyse Bewertung Neuartiger Lebensmittel
Neuartige LM Tox LM mit neuer Struktur
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
47
Phytosterine Beispiel Antraumlge
Sicherheitsbewertung
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
48
Kritik EFSA zb Danacol
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
49
LM aus nicht traditionellen Rohstoffen
Zb Lycopin
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
50
LM pflanzliche Sekundaumlrstoffe
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
51
LM ethnic
Food Allergy - Definition
bull Must be differentiated from food intolerances and
other adverse food reactions
bull Key components of food allergy
bull An immunologic response to a food protein
(food intolerances usually related to
carbohydrates)
bull Exquisitely small amounts may cause a
reaction
bull Reactions can be severe and even life-
threatening
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
52
Exposure
Sensitization
Symptoms
Genetic Predisposition
Re-exposure
Food Allergy - Prevalence
bull 5 ndash 7 of young children
bull 2 ndash 3 of adolescents and adults
bull At least 11 million Americans are affected
bull Prevalence appears to be rising (sharply)
Common Food Allergens
Children Adolescents Adults
Milk Peanuts
Egg Tree Nuts
Peanut Fish
Soy Shellfish
Wheat
Tree nuts
Food Allergy ndash Signs amp Symptoms
bull Range from chronic low grade symptoms to acute life-threatening reactions
bull Hives angioedema
bull Eczema
bull Vomiting diarrhea poor growth
bull Cough congestion
bull Wheezing breathing difficulty
bull Hypotension shock
bull Anaphylaxis ndash A systemic allergic reaction
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
53
Food Allergy - Urticaria
bull Rarely a cause of chronic urticaria
bull More common in acute urticaria
bull Peanuts nuts eggs milk fish shellfish most common
bull Usually occurs within 2 hrs of ingestion (history often diagnostic)
bull May have angioedema and associated GI resp Sx
Definition of Anaphylaxis
bull Systemic allergic reaction
ndash Multiple organ systems may be involved
bull Acute onset
bull IgE mediated
bull Manifestations vary from mild to fatal
bull May be uniphasic biphasic (30-40) or
prolonged (rare)
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
54
Atopic Dermatitis - Food Allergy
bull 40-50 of patients with severe AD have food
allergy as a major trigger
bull Food allergy in 20-25 with less severe AD
bull Egg allergy is most common followed by milk
peanut soy wheat and fish
bull These 6 foods account for 80-90 of food
sensitivities in AD
bull 36 react to one food 26 to 2 foods 18 to 3
foods 10 to 4 foods 10 to 5 or more foods
Gastrointestinal Food Hypersensitivity
IgE-Mediated
Non-IgE-Mediated
Immediate GI hypersensitivity
Oral allergy syndrome
Allergic eosinophilic esophagitis
Allergic eosinophilic gastritis
Allergic eosino gastroenteritis
Enterocolitis syndrome
Dietary protein proctitis
Celiac Disease
The Diagnosis of Food Allergy
bull Detailed history
bull Food(s) suspected
bull Specific symptoms
bull Timing of symptoms
bull Reproducibility of reaction
bull History may be diagnostic with some acute
reactions but overall will be verified only 30 ndash
40 of the time (especially in AD and GI
syndromes)
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
55
The Diagnosis of Food Allergy
bull High rate of false positive skin tests and
RASTs (poor positive predictive value)
bull High negative predictive value (for IgE-
mediated syndromes)
bull Must be carefully interpreted in the context
of the clinical picture
bull Oral challenges are the only tests that are
more (but still not completely) definitive
Food Allergy - Diagnosis
Detailed History
IgE-mediated Non-IgE-mediated
Challenge orSkin test or RAST Endoscopy
(+) (+) (-)(-)
Stop Elimination Diet Stop
(-) (+)Done
Food Challenge(s)
(+) (-) Stop
Specific elimination diet
Conclusions and Dilemmas
bull Food allergy is common and potentially deadly and
avoidance is currently the only treatment option
bull Strict avoidance is essential to help prevent reactions and
possibly to help promote the outgrowing process
bull Food challenges are a useful means to diagnose food
allergy (and determine threshold doses)
bull However challenges are limited in 2 ways
bull The most allergic patients must be included
bull Determination of threshold doses for chronic food
allergic conditions especially those that are not IgE
mediated is likely impossible
Intolerances are not allergy( Allergy via IgE )
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
56
Food Intolerances non IgE Intolerances many confusing tests
Personalised Nutrition fuctional foods epigenetic and health claim regulation
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
57
Labelling
Pre-packaged foods have information on their labels which can help consumers choose between different foods brands or flavours
Much of the information must be provided by EU law
bull Directive 200013EC on labelling presentation and advertising of foods applies until 12122014
bull Regulation (EU) No 11692011 on the provision of food information to consumers will apply from 13122014 (sometimes referred to as EU FIC)
Health Claim regulationInformation for consumers
The following information must appear by law on food labelsbull the name of the foodbull weight or volumebull ingredient listbull allergen informationbull genetically modified (GM) ingredientsbull date mark and storage conditionsbull preparation instructionsbull name and address of manufacturer packer or sellerbull place of originbull lot (or batch) markbull nutrition information (from 2016 onwards)
Additional information may also be provided such as cooking instructions or serving suggestions
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
58
Nutrition information
At the moment foods and drinks do not have to provide nutrition information on packaging (unless they make a nutrition or health claim about the product) Where information is given some rules have to be followed
However provision of information will become compulsory from 13th December 2016 and there will be some small changes to the format required
Current labelling regulations in Europe
The current rules specify the nutrients that can be included The information has to be presented per 100gml but could also be provided per portion
Further information can be added to labels such as the amounts of polyunsaturates monounsaturates starch cholesterol vitamins or minerals
Format 1 lsquoBig 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)Fat (g)
Format 2 lsquoBig 4 and Little 4rsquoEnergy (kJ and kcal)Protein (g)Carbohydrate (g)of which sugars (g)Fat (g)of which saturates (g)Fibre (g)Sodium (g)
New labelling regulations in Europe
A new Regulation covering all aspects of food labelling including the size of the letters on packaging came into force at the end of 2011
It will make providing nutrition information on the back of packaged foods compulsory from 2016 (previously it was optional unless a nutrition or health claim was made)
The format of nutrition labels will change slightly under the new rules and companies can start to use the new format straightaway although the old rules (known as the Food Labelling Regulations) remain legal until 2014
New labelling regulations in Europe
Current back of pack nutrition panel New back of pack nutrition panel
Note that fibre can also be added to the panel but is not compulsory
Per 100g
Energy 1500kJ356kcal
Fat 74g
of which saturates 11g
Carbohydrates 581g
of which sugars 168g
Protein 99g
Salt Below 01g
Per 100g
Energy 1500kJ356kcal
Protein 99g
Carbohydrates 581g
of which sugars 168g
Fat 74g
of which saturates 11g
Fibre 89g
Sodium Below 01g
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
59
New labelling regulations in Europe - Reference intakes
The new regulations feature Reference Intakes (RIs) RIs replace what used to be called Guideline Daily
Amounts (GDAs) in the UK It should be noted that the notion of RIs is different from the notion of guideline daily amount as the term reference intake does not imply a nutritional advice unlike the term guideline
There is no nutritional advice to consume for example 20 g of saturated fat per day and consumers should not believe it is a minimum quantity necessary to maintain health RIs for energy and other selected nutrients are shown is the chart
Nutritional information can be provided as a percentage of the RI
Energy or nutrient Reference Intake
Energy 8400kJ2000kcal
Total fat 70g
Saturates 20g
Carbohydrate 260g
Sugars 90g
Protein 50g
Salt 6g
New labelling regulations in Europe
Nutrients will have to be listed in a certain order ndash energy (both in kJ and kcal) and the amounts of fat saturates carbohydrates sugars protein and salt (in place of lsquosodiumrsquo which is no longer permitted)
The information has to be given in per 100gml but can additionally be given
bull Per portion or per consumption unit (eg per slice)
bull As Reference Intakes
Information of the following nutrients can be provided in a voluntary basis mono and poly-unsaturates polyols starch and fibre Information on certain approved vitamins and minerals can be listed if present in significant amounts
If a nutrition claim is made it becomes mandatory to give information about that nutrient even if it is not listed in the regulation For example if the claim lsquohigh in omega 3rsquo was made then the amount of omega 3 per 100g would have to be given
Nutrition and health claims
The Regulation (EC) No 19242006 on nutrition and health claims is enforced across the EU The regulation implements measures to ensure that any claim made on foodrsquos labelling presentation or marketing is clear accurate and based on evidence accepted by the whole scientific community
Foods bearing claims which could potentially mislead consumers are eliminated by the market In order to bear claims foods have to have appropriate nutrient profiles which are set This regulation helps to enhance the consumers ability to make informed and meaningful choices
Nutrition and health claims
General claims about benefits to overall good health such as lsquohealthyrsquo or lsquogood for yoursquo will only be allowed to be used if accompanied by an appropriate and approved claim This means that more general claims must be backed up by an explanation of why the food is lsquohealthyrsquo or what makes it a lsquosuperfoodrsquo
Labels are not allowed to claim that food can treat prevent or cure any disease of medical condition These sorts of claims can only be made of licenced medicines
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
60
Nutrition claims
A nutrition claim is any claim which states suggests or implies that a food or drink has particular beneficial nutritional properties There are certain conditions around the usage of each nutrition claim
Examples of approved nutrition claims
bull Low fat (less than 3g of fat per 100g food)
bull High fibre (at least more than 6g of fibre per 100g food)
bull Reduced sugar (30 less than the original product)
bull Source of vitamin C (at least 15 of the recommended daily allowance for vitamin C)
Health claims
A health claim is a statement about the positive effect a product can have on health Claims appearing on food labelling have to be approved by the European Food Safety Authority (EFSA) who evaluate the scientific evidence supporting health claims
Examples of health claims include
bull Calcium is important for the maintenance of normal bones
bull Beta-glucans contribute to the maintenance of normal blood cholesterol levels
bull Iron contributes to the reduction of tiredness and fatigue
Types of health claim
There are three different types of health claims
bull lsquoFunctionrsquo or Article 13 health claims These health claims either relate to the growth development and functions of the body refer to psychological and behavioural functions or refer to slimming and weight control
bull lsquoRisk reduction claimsrsquo or Article 14(1)(a) health claims These are health claims on reducing a risk factor in the development of a disease
bull Health claims referring to childrenrsquos development or Article 14 (1)(b) claim
Phenotyp Krankheiten Genetik-Umwelt
TotallyGenetic
TotallyEnvironmental
Struck
by
lightning
Motor
vehicle
accident
Duchenne
muscular
dystrophy
Cystic
fibrosis
Heart
disease
Cancer Schizophrenia
Diabetes
ObesityAsthma
Rheumatoid
arthritis
PKU
AlzheimerrsquosFragile X
Autism
TB
Meningococcus
Multiple
sclerosis
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
61
Anstieg komplexer Erkrankungen Was veraumlndert sich in der Umwelt
242
Missing heritability Genetik erklaumlrt nur ldquowenigrdquo Gen-Umwelt
Interaktionen wichtiger Epigenetik
Break trough Epigenetik Agouti mice genetisch ident epigenetisch unterschiedlich Einfluss Ernaumlhrung Transgenerationale Effekte
The environment toxins influence epigeneticmaschinery
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
62
The environment stress influencesepigenetic control of gene expression
Rev Dev Psychobiol 2010
Epigenetics
bull Epigenetics refers to the study of changes in the regulation of gene activity and expression that are not dependent on gene DNA sequence
bull While epigenetics often refers to the study of single genes or sets of genes epigenomics refers to more global analyses of epigenetic changes across the entire genome
Epigenetic Mechanisms
Gene Expression
RNA Interference
Histone Modifications DNA Methylation
Epigenetik Zwillingsstudien
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
63
Epigenetik Intervention PflanzeninhaltsstoffeDiscussion hypothesis diets effect epigenetic regulation ofinflammation DNA damage ageing(also) via GI-microbiota- metabolites
Nutrition
GI microbiota metabolites egSCFAs
Epigenetic regulation
Inflammation DNA damage ageing
Most complex diseases microbiota involved
If you bdquogoogleldquo microbiota + any complex disease and you find noscience results for a specific disease please tell me
Gesundheit Rolle der (GI)- Microbiota our commensals in the gut
bull Microbiome
bull 10 -100x more information than the human genome
252
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
64
From plating of living bacteria to analysis of (r)DNA ofbacteria
Major groups of the human microbiome
Elements of the gut brain axis bacterialmetabolites from the gut through the blood intothe brain
GI microbiota (Gene) diversityhighly desired
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
65
Ways of delivery and microbiota a long lasting difference
Infants born by elective cesarean delivery had particularly low bacterial richness and diversity formula-fed infants had increased richness of species with overrepresentation of Clostridium difficile
CHILD involves more than 10 000 people including 3 500 infants
Microbiota change in life time
259
Microbiota and fermentation productseg SCFAs
(Louis and Flint 2009 FEMS)
Clostridial cluster IV
(Rumminococaceae)
Clostridial clusterXIVa
(Lachnospiraceae)
Faecalibacteriumprausnitzii
Butyricoccus
Clostridium Leptum
Eubacterium hallii
Anaerostipes coli
Roseburia spp
E rectale spp
Resistent starchNon starch
Polysaccharides
SCFAs bind to G-Protein-Receptors 4143 (FFARs) on Immune cells Adipocyteshellip
Anti-inflammatory
Inhibition of NFκB(Huster et al 2013 Flint et al 2009 Nature Rev)
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
26042017
66
Understanding Health OMICSMetabotypes and OMICSThe kind of metabolism that an individual has
Personalised preventive nutrition functionalfoods or food pyramide for all Safety
