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Cancer therapy: Up close and personalized

Gerard Evan reviews an inspiring, at times frustrating, chronicle of the war on cancer by one of its generals.

The Death of Cancer Vincent T. DeVita and Elizabeth DeVita-Raeburn. Sarah Crichton: 2015.

9780374135607

The 1971 US National Cancer Act, which effectively declared a 'war on cancer', was the product of a confused era. During the cold war, extreme pessimism and extreme optimism were constant, if unlikely, bedfellows. As long as we didn't blow ourselves up, anything was possible — even curing cancer. In the years since, Vincent DeVita has been both a key participant in and a witness to this war, as director of the US National Cancer Institute (NCI), physician-in-chief at Memorial Sloan Kettering Cancer Center in New York City and director of the Yale Cancer Center in New Haven, Connecticut. In The Death Of Cancer, he and his daughter, the accomplished science journalist Elizabeth DeVita-Raeburn, write of this period with passion and insight. It is a deeply personal account, often inspiring, sometimes confusing and occasionally unedifying.

A woman has cancer radiotherapy at Oak Ridge Institute of Nuclear Studies, Tennessee, in the 1950s. Credit: Mondadori Portfolio via Getty

DeVita opens with the story of his friend Lee. Lee's protracted encounter with aggressive prostate cancer encapsulates the book's principal thesis: that the treatment of cancer is frequently ill-informed, too conservative and mired in the timidity of local and national bureaucracies. DeVita makes an unassailable case that advances come from people with courage, vision and tenacity, rare virtues too often confused with risk-taking and stubbornness in today's blame-addicted society.

Lee's cancer follows a well-trodden course, initially responding to therapy, but over time, and under the selective pressure of drugs, evolving into a refractory, terminal disease. DeVita uses his abundant connections to see that Lee receives exceptional personalized care — radiotherapy in the best cancer hospitals and unprecedented access to experimental drugs. Through this heroic effort, Lee survives for 12 years. Yet with this narrative, DeVita also opens a can of worms. He shows that the standard of care can be improved. But a uniquely well-connected ex-head of the NCI personally stewarding someone's treatment is personalized medicine for the super-elite (and the cost be damned).

It is also irritating to see DeVita fall into the teleological trap of endowing cancer with baleful purpose. He describes cancer cells as “canny” and “smart” — they “learn to outwit” therapy and “figure out” ways of surviving. Poppycock. Cancer progression and the emergence of resistance are the results of goalless evolutionary processes, not calculated intent. Imbuing cancers with malign purpose terrifies patients and is shoddy biology.

After Lee, we enter the barbaric world of post-First World War cancer treatment, when crude surgery and even cruder radiotherapy ruled. We then meet JD, a Polish immigrant with lymphoma and the first person to get chemotherapy for cancer. In 1942, he was admitted to what is now Yale–New Haven Hospital, where, having previously failed radiotherapy, he was pumped with nitrogen mustard (also known as mustine). His cancer shrank to nothing, but the chemotherapy killed him. From such an unprepossessing start, it took guts to bear the chemotherapy torch and, given the toxicity of the agents, even more guts to use them in combination.

DeVita tells an engaging tale of how combination chemotherapy was developed at the NCI, and of his pivotal role. The NCI, a quasi-independent juggernaut of the National Institutes of Health, was tasked with overseeing prosecution of the National Cancer Act. We meet the remarkable Emil 'Tom' Frei, NCI chief of medicine, and Emil 'Jay' Freireich, who ran the children's leukaemia ward. They developed the first cure for childhood leukaemia, and coined the first of the snazzy acronyms: VAMP, a brew of vincristine, amethopterin, 6-mercaptopurine and prednisone. In 1972, DeVita, Frei and Freireich were among the recipients of the Albert Lasker Clinical Medical Research Award for their work.

They did not have an easy time of it. DeVita paints a depressing picture of internecine strife in oncology, fuelled by a preoccupation with status and status quo at the expense of innovation. Be warned: this is a very personal tale of political manoeuvring, with a large cast of heroes and anti-heroes. I recommend noting down the names as you go.

DeVita became director of the NCI in 1980. He had the thankless task of replacing a grace-and-favour establishment with something approaching a meritocracy — guaranteed to elicit some lifelong enmity. He also presided over the maturation of combination chemotherapy from an empirical mix of poisons into a modern, evidence-based process, undoubtedly saving millions of lives.

Yet here, as with the section on Lee (and for much the same reason), DeVita's narrative occasionally raised my hackles. The 1960s and 1970s were complex and difficult: a dearth of cancer drugs, mechanisms and vision was seasoned with vested interests and institutional insecurity. But DeVita describes a world where influential doctors used their power to demand favours of each other and their underlings — a system in which he participated. This is not a reassuring depiction of medical practice. Of course, it is impossible not to admire the passion, optimism and dedication that course through this book, and I applaud every success among patients for whom DeVita cared personally. But we must never forget that the best cancer therapies need to be made available to everyone, at a cost that patients and society can afford.

The war on cancer is often compared unfavourably to another great US science initiative, the Apollo lunar programme. This is unfair. Both required almost superhuman ingenuity and effort, but landing a man on the Moon was principally a problem of engineering and organization. By contrast, despite 45 years of insight into the molecular processes of cancers, we still do not really know how therapies exploit cancers' vulnerabilities, or even why such vulnerabilities exist. Every day, we use targeted drugs to block mutations that drive cancer cells but, remarkably, we still fail to understand why that kills them. It is ironic, then, that former US president John F. Kennedy's prophetic words about the Moon mission best describe our enduring struggle against cancer: “The greater our knowledge increases, the greater our ignorance unfolds.”

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Evan, G. Cancer therapy: Up close and personalized. Nature 527, 162–163 (2015). https://doi.org/10.1038/527162a

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