580 I R I S H J O U R N A L O ~ M E D I C A L S C I E N C E

MURRAY, JAMBS JOSEPH. Educated University College, Dublin. M.B., B.Ch., B.A.O., 1919 (N.U.I.). M.O.H. Carbery, Co. Kildare. Died July 17, 1943.

NEL, CICBRO GARNETT. Educated T.C.D. B.A., B.Ch., B.A.O., M.B., 1926. Formerly Clinical Assistant, Central London Ear. Nose and Throat Hospital. In practice at Oudtshoorn, S. Africa Died September 25, 1942.

O'RYAN, PIBRCB WILLIAM. Educated T.C.D. Lie. Med. and Surg., Dublin, 1932. Died at sea, July 21, 1943.

0'REILLY, THOMAS MICHAEL. Son of Michael O'Reilly, B.B., B.Ch., B.A.O., 1940 (N.U.I.). In practice in Killarney, Co. Kerry. Died at Waterville, June 17, 1943.

RICB, JOHN POYNTZ. Educated in Cork and Dublin. L.R.C.P. & S. (Edin.), 1883. M.O. Castleisland Dispensary District, Co. Kerry. Died June 12, 1943.

PERRY, SAMUEL JAMBS CHATTERTON PRITTrE. Son of William Perry, bern in Dublin, March 4, 1868. Educated at High School and T.C.D. L.R.C.P. & S.I., 1892; F.R.C.S.I. , 1901. Lt., R.A.M.C., 1892; Lt.-Col., 1916. Service N.W. Frontier, 1897-98. Died at Hove, May 3, 1943.

S~ACK, H~NRY THOMPSON. Born in Dublin in 1880, son of Richard Theodore Stack, M.I)I; F.R.C.S.I. Educated in T.C.D. B.A., 1901; M.R., B.Ch., R.A.O., 1902; D.P.H., 1911 (Dub.); D.M.R.E. (Cant~b.), 1926. Late Civil Surgeon, 8. Africa and Major, R.A.M.C. O.B.E. Died in London- derry, March 4, 1943.

TRANT, JAMBS. . ~. Born in Listewel, Co. Kerry, October 24, 1865. Educated at ~u. ~rendan's, Killarney, and Ledwich School, Dublin. L.R.C.P. & S.I., 1887; F.R.C.S.I., 1900. M.O. Derrynane Dispensary District. Died at Waterville, Co. Kerry, December 13, 1942.

V~mAN, HXL~A MAUD: ,Educated T.C.D. B.A. (as Marsh), M.B., B.Ch., B.A.O., 1915; M.A. and M.D., 1919. Late House ~ r g e o n Royal Devon and Exeter Hos- pital. Married Amos George Varian, M.D. (Dub.). Died July 1, 194,3.

VAVA SOuR-LANE, ALFRED. Born at Wyzeerabad 2 April 24, 18~4. Educated R.C.S.I. L.R.C.S.I., 1877~ L.R.C.P.I., 1878~ M.R.C.P.I., 1889. Entered Army Medical Serwce July, 1881; Major, 1893; Lt.-Col., 1901. Retired 1906. Ser- vice Egypt 1882-84. Died in London, July 18, 1943.

KARL LANDSTEINER. THE SIGNIFICANCE oF HIS WORK IN MEDICINE.

The death of Dr. Karl Landsteiner, which took place on 26th June, 1943, in New York, marks the loss of one of the most eminent pathologists and medical research workers. His name had first become familiar by his discovery of the blood groups which placed him in the rank of the benefactors of mankind and for which he was rewarded by the Nobel Prize. But the significance of his work went immensely beyond this special chapter of serology. His investigations concern many problems of pathology and reflect at the same time the develop. ment of immunology and serology to the position in which they stand to-day.

Landsteiner was born in Vienna (14th June, 1868) where he graduated in Medicine and lived till 1919, working at the Department of Hygiene (Gruber) and at the Department of Pathology (Weiehselbaum), later as pathologist at several hospitals and as a lecturer at the University. In 1919 he left Vienna for the Hague, and in 1922 he was called to New York as a member of the Rocke- feller Institute for Medical Research, where he was given a liberal opportunity of continuing his work. He was honoured by the membership of many scientific Academies and Societies. I t may only be mentioned that he was a foreign Member of the Royal Society and an honorary Member of the Pathological Society of Great Britain and Ireland.

KARL LANDSTEINER 581

Strange to say, Landsteiner made his world-famous discovery of the human blood groups as early as 1900-01, but nevertheless was induced to leave his native country nearly twenty years later, apparently for economic reasons. One also may wonder why he was awarded the Nobel Prize for this discovery only in 1930. According to the statutes, the Nobel Committee in awarding the .Nobel Prize for Medicine gives consideration not only to the newest results which have been of the greatest significance for mankind in the past year, but also to previous discoveries the importance of which has been proved only recently. Landsteiner 's work on the blood groups actually forms an interesting example of the long period during which a fundamental discovery may lie dormant before its influence on theoretical science and practical application comes to be recog. nised.

To understand this delay it may be recalled that the differentiation of human and animal blood, and mere so tha t of the blood of different human individuals, seemed impossible before 1900. Even at that date these observations were still to be considered fully unexpected, though interesting from the biological point of view, and their extraordinary practical significance was not yet to be realised. Furthermore, it must be taken into consideration tha t the laws of heredity, though recognised in principle by Gregor Mendel in 1866, had long been forgotten, only to be re-discovered in 1900. Thus the knowledge of blood groups and tha t of genetics began simultaneously but without any foresight of the close connection between the two. Not until 1910 was the hereditary character of the blood groups proved by von Dungern and Hirszfeld, and only in 1924 was the correct theory of their heredity elucidated by Bernstein. Since then we have come to recognise tha t in man the blood groups are the qualities which by simple experimental investigations demonstrate most impressively the Mendelian laws of inheritance. Again it may be noted that the regular distribution of blood groups and its deviation in different parts of the world, also dependent on heredity, were discovered only in 1919 by L. and H. Hirszfeld. The hereditary character not only concerns the groups in the classical A B e system, but also the other types, the most important being the M, N and P. factors and recently the Rh factor, all of which were brought to light by Land- steiner and his colleagues (Levine and Wiener, 1927 and 1940). In addition we may mention investigations into irregular agglutinins, cold agglutinins, the sub-groups and many single observations as parts of the great work evolved by Landsteiner, which link his name for ever with the knowledge of blood groups. Thus it is to Landsteiner 's credit that blood transfusion has become after so many misadventures a perfectly reliable therapeutic measure serving to save innumerable lives. He realised already in 1901 tha t the individual blood differences might explain the changing consequences of transfusion. I t should be noted, however, that the first trausfusions on the basis of blood group deter- ruination were made so lately as 1908 by Ottenberg and that the general use of selected donors for transfusion was definitely established only during the world war (1914-1918). Hence the real recognition of Landst, einer's discovery came to be developed in the third decade of this century. Only by this time had its influence become evident in physiology, pathology, genetics and in the problems of forensic medicine, disputed parentage and of anthropology.

Landsteiner 's laconic report of his first observations in 1900 is in contrast with their outstanding significance. They are recorded in a few lines in a foot- note to a paper and o.nly demonstrate tb.st t h e serum of health>y persons may not only agglutinate an'm, lm, l r e d ce]Js but also hnrN_~n red cells of other individuals. Here Landsteiner adds indeed tha t i t is still to be decided whether this phen- omenon is caused by o l ~ n a l individual d i f f ~ n c e s or by the influence of damage, perhaps of bacterial ua tu~ . The decis/on w a s a l l t h e more difficult since Landsteiner encountered this belmviour Imrticularly when u~ng blood originating from individuals suffering from severe ~ . The work on isolytie immune sera was published shortly after by Ehrlieh and Morgenroth. They showed tha t by immunisation of goats with the red cells of other goats isoantibodies are produced which act on the red cells o f s o m e i n d i v i d u a l s b u t n o t o n those of others. Physiological ~ b e t w e e n the blood of different individuals within the same species have been proved in this way. These investigations were continued quite independently and yielded in the following year (1901) the existence of three blood groups (O, AI ]3). I n 1 M 2 the rare fourth blood group (AB) w a s d i scovered b y y o n Decas teUo a n d Sturli on the immediate suggestion of Landsteln~. Thus w e r e e s tab l i shed the two fundamental rules of Landstelner, first the dependence of the differentiation upon two antigens (A and B) and secondllr the regular presence or absence of the iso-agglutinins (anti-A and anti-B) when the corresponding antigens are missing and present respectively.

5 8 2 I R I S H J O U R N A L O F M E D I C A L S C I E N C E

Although Landste iner ' s name is pr imari ly connected wi th the knowledge of blood groups, this is nevertheless only a small share of the work accomplished by him. Well known are his investigations into the syphilitic infection of monkeys (with Finger, 1905), his research on the ~etiology of poliomyelitis (first t ransmission on monkeys, wi th Popper (1909) independent ly proved by Flexner and Lewis) and the proof t h a t the pathogenic agent is a virus of very. small size (with Levaditi , 1910). Noteworthy is his elucidation of the patho. genesis of paroxysmal h~emoglobinuria caused by cold-antibodies (wi~;h Donath , 1904) and his observat ion t h a t alcoholic extracts from the tissues of hca l thy animals may be used as antigens for the Wassermann reaction (with Muellcr and Poetzl, 1907) as they generally are to-day. Apar t from m a n y other problems dealt wi th in Landsteiner 's work, special a t t en t ion mus t be called to his con- t inuous investigations into the mechanism and specificity of serological reactions. I t is wor thy of ment ion t ha t Landsteiner observed independent ly of Border the formation of specific h~emolytic antibodies on immunlsat ion and t h a t he prepared for the first t ime immune sera against spermatozoa (1899).

Since the beginning of this century he was engaged on research work on the theory of antigenic structures and ant ibody-react ivi ty. While he was a t first inclined to criticize to a certain degree Ehrl ich 's original chemical in terpre ta t ion and in a measure to favour physico-colloidal contemplations, he was in la ter t imes himself able to prove beyond doubt by his remarkable work on chemo. specific antigens the pr imary chemical na ture of ant igen-ant ibody reactions and the dependence of serological specificity on chemical consti tut ion. Whi l s t Obermayer and Pick had only gone so far as to show t h a t the specificity of proteinic ant igens m ay be al tered by the action of substances such as nitr ic acid, ni trous acid and iodine, Landsteiner developed the knowledge of chemo- specific antigens to an astonishingly high level, demonst ra t ing t h a t i t is possible by suitably a t taching simple chemical compounds of any kind to proteins to prepare artificial conjugated antigens for immunlsat ion. The chemical com- pounds may, however, by themselves also exert specific reactions i n v i t ro , par . t icularly by inhibi t ing the reaction between the conjugated antigens and the i r antibodies. I n this way i t was even possible, e.g., to prove t h a t stereo-isomeric compounds m a y be dist inguished serologically. The lhni ts to which such serological chemistry m a y yet ex tend cannot a t present be defined. Another principle discovered by Landsteiner is the so-called combinat ion-immunisat ion. Fract ions of antigens, e.g., alcoholic extracts from tissues containing the Forss- m a n heterogenetic ant igen which show specific serological react ivi ty i n v ~ r o bu t which are unable to induce an t ibody formation will, when combined wi th proteins foreign to the species to be immunised, become full antigens acting on immunisat ion i n r i v e . The split products only combine wi th the an t ibody without being sufficient for immunisat ion. For this reason they have been called " haptens '" by Landsteiner. The knowledge of haptens has opened up an interesting and wide field of serological research.

Beyond doubt these discoveries and the investigations following upon t hem have brought to light revolut ionary aspects of immunological reactivity, formerly believed to depend only on proteins. They are no t only of the greatest interest in the theoretical explanat ion of antigenic specificity and an t ibody action the chemical character of which has become firmly established by Landstoiner 's research work ; they also have a prominent significance for medical problems, proving as they do t h a t nearly every chemical substance m a y be a pre-stago (hapten, semi-hapten) of an ant igen and m a y become antigenic under suitable conditions. I t is evident t h a t such a mechanism may explain cer tain kinds of hypersensit iveness in man. I t is especially to the discovery ofcomplex chemospecifio antigens and to the recognition of chemospecific anaphylaxis t h a t we are indebted for the development of a general concept which is able to explain anaphylaxls , allergy hypersensitiveness and idiosyncrasy from the same or a simi|~r point of view.

Thus Landsteiner 's work, pr imari ly characterlsed b y scientific research bearing most ly on theoretical questions, contr ibuted great ly to diverse clinical problems. I t is .significant for this great sm'entist t h a t he was not searching immediately for pract ical application. He was one of the research workers who are aspiring af ter science and its perc. eption independent ly of .practical purposes. Thus in the scmnces of serology and mamunology many investigators oy worg, ng solely from the theoretical s tandpoin t have by their researches automat ical ly influenced in an admirable and indeed surprising manner the progress of pract ical aspects of medicine. So did Landstoiner : he belonged to those scholars for whom the aim of science is first of all the honour of the h u m a n spirit.

H. SAc~s.