Obituary

304 www.thelancet.com Vol 382 July 27, 2013

Emil Frei IIIOncologist and pioneer of combination chemotherapy. He was born in St Louis, MI, USA, on Feb 21, 1924, and died in Oak Park, IL, USA, on April 30, 2013, aged 89 years.

When Emil Frei joined the US National Cancer Institute (NCI) in 1955 it was to research childhood leukaemia in the hope of devising improved treatments. Thanks to the pioneering work by the paediatric pathologist Sidney Farber, clinicians had a handful of drugs that were eff ective—but, in many patients, for only a limited period. Thereafter drug-resistant cells would emerge, and the disease would reassert itself. David Nathan, now a Distinguished Professor of Paediatrics at Harvard Medical School but then a young intern at NCI, recalls the dilemma. “The argument in cancer at that time was whether one should use single agents sequentially, allow resistance to come up and then treat with a second drug, or whether the way to do it was by combination therapy which might kill all the cancer cells but was very toxic.”

NCI’s then Clinical Director Gordon Zubrod believed in combination chemotherapy. He urged the newly appointed Frei, together with his colleague Emil J Freireich, to investigate its use in leukaemia. They did so, although the early results were not always encouraging. “It didn’t work for years”, says Nathan. “But fi nally they developed a treatment programme with four agents that started to lead to permanent remissions and cures. It was very impressive because they had to put up with a lot of criticism. But they persisted. And they were right.” Some of their peers were disinclined to accept the new approach. “In the early 1960s,

or even the later 1960s, it still wasn’t accepted by all”, says Professor George Canellos of the Department of Medicine at Harvard Medical School who fi rst met Frei during that period. “People were still terrifi ed of the toxicity. But the therapeutic results were much, much better.” The importance of Frei’s work was recognised in a 1972 Lasker Award.

Emil Frei was the third generation of his family to bear both those names. But he broke with tradition by not following his father and grandfather into the successful family business of designing and making stained glass windows. An interest in science dating from his teenage years was initially curtailed by the outbreak of World War 2. He served in the US Navy Medical Corps which fi rst sent him to Yale to train as a doctor, then deployed his skills in the Korean war. Only then was he able to join NCI as a clinician researcher, eventually becoming its Chief of Medicine. He stayed with NCI for a decade. “It was there he did his greatest work”, says Nathan. In 1965, Frei moved to MD Anderson Hospital at the University of Texas and, 9 years later, to Harvard’s Dana-Farber Cancer Institute as Physician in Chief until his formal retirement in 1991.

During his time at Dana-Farber Cancer Institute Frei pioneered the chemotherapy of non-Hodgkin lymphoma in adults and embarked on many other major programmes including one in collaboration with Boston Children’s Hospital to tackle osteosarcoma. More generally he oversaw a transformation in Dana-Farber itself. “When he arrived in 1972 it was in a crowded, small building and largely unknown to the city”, Canellos recalls. “We had just a few beds for adult cancer patients. Now we have about 150.” The number of staff increased some sixfold. What he brought to Dana-Farber were the organisational skills he’d learned from Zubrod at the NCI. Zubrod had insisted that besides practising combination therapy Frei should train other people and seek to collaborate. It was an outlook he had already taken to MD Anderson Hospital where his department of developmental therapeutics became the forerunner of its Clinical Research Center. “At Dana-Farber he was really a breath of fresh air”, says Canellos. “He started teaching people about teamwork. He built up its basic science, biostatistics, epidemiology, and immunology. He did a wonderful job.”

Frei, always known to friends as Tom, had a lot of curiosity, says Nathan. “There was no challenge that Tom didn’t like to take. He was a very kind man and generous, particularly to his juniors. He cared about people’s careers. And he was great teacher.” Canellos describes him as “a man ahead of his time”: Frei had a vision of cancer treatment based on understandings of tumour biology that would one day make it possible to develop more eff ective and less toxic drugs. “Tom used to say, ‘We’re here to move the fi eld’. That was his mantra.” Frei developed severe Parkinson’s disease and Canellos describes the last 10 years of his life as very diffi cult. Frei leaves a son and four daughters by two marriages.

Geoff Watts

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