The excitement and pioneering spirit of the early drug war on cancer is captured in this triumph of medical writing, writes JOHN CROWN
TVARDOVSKY, the Soviet literary editor, famously got up out of bed after starting a nocturnal browse of Solzhenitsyn's A Day in the Life of Ivan Denisovich, changing his pyjamas for his best suit and tie in order to accord the book the respect which he quickly decided it merited.
The Emperor of all Maladies: a Biography of Cancerby Siddhartha Mukherjee, a young New York cancer specialist, deserves such respect.
At its core is a conventional history, a chronologically-ordered narrative of cancer across the centuries, told as a series of individual vignettes. Each section illustrates some advance in the understanding of the disease.
There is Percival Pott, the London surgeon, who made the connection between scrotal cancer in chimney sweep boys (surely the worst job of all time) and soot as a carcinogen. Medical students might be inspired by Emil Grubbe, himself a student of just 21 years of age when he conceived and executed the strategy of treating cancers with radiation.
These accounts often detail the personal story of those whose work is highlighted, such as that of William Halsted, the brilliant, imperious but also drug-addicted 19th-century Baltimore breast surgeon. There is George Papanicolaou, the young Greek doctor and developer of the “Pap smear” test, who, when he first emigrated to the United States, worked as a hospital porter and a carpet salesman, because he was not granted American medical registration.
It is salutary to note that Papanicolaou’s initial research into the smear test (which has probably saved millions of lives worldwide) took place in the 1920s, and was widely accepted by the 1950s. Ireland introduced routine Pap screening in the 21st century.
This “biography” of cancer is interspersed with the evolving narrative of Carla Reed, a contemporary patient of Mukherjee’s, and with recurring visits to the life and career of Dr Sidney Farber, a pioneering cancer specialist who was “the father of chemotherapy”.
Farber, who defied the nihilism of his time by treating childhood leukaemia with drugs, is the central figure of the book, and his work is taken as a metaphor for the advances and for the blind alleys that characterised much of cancer research in the 20th century.
Farber emerged on the cancer research stage in the aftermath of the second World War, a time when leukaemia was seen as a death sentence, but also a time when the potential of medical research seemed limitless.
To understand the direction that the war on cancer took at this stage, one needs to understand the medical context of the time. Progress had been substantial.
Infectious diseases, those ancient scourges of humankind, were proving susceptible to effective prevention and treatment (although the hubris that was associated with the supposed “conquest of infection” was subsequently unmasked by HIV/Aids). Major surgery including operations on the brain and heart were now routinely available and generally safe.
Many in the US simply could not understand why cancer was not succumbing to the might of medical research in the same way that infection and other diseases had. Surely a society which could develop the atomic bomb could develop a technology to cure cancer?
Ironically, it was the chemical weapons programmes of the war years that led to chemotherapy. The discovery that American sailors, who were exposed to the chemical warfare agent mustard gas and developed low white blood counts, prompted the speculation that the same chemical could treat leukaemia, which is a cancer characterised by an excess of abnormal white blood cells.
Farber was a pioneer of this approach, and shocked the medical world with his reports that dying leukaemic children were being restored to health, albeit usually temporarily, with “chemotherapy” treatments based on these weapons.
Suddenly, cancer research and the US government had a goal, to extend the benefits of chemotherapy to the other, more common, cancers. The government invested heavily in the “National Cancer Institute”, and its drug discovery programme over the 1950s and 1960s and several national networks of hospitals and medical schools called “co-operative groups” were funded with the express purpose of testing novel chemotherapies.
Soon hints were emerging that a whole range of cancers were to a greater or lesser extent (usually lesser) susceptible to these inelegant, non- specific and highly toxic drugs. Farber, the philanthropist Mary Lasker and others lobbied Congress, and their efforts resulted in the National Cancer Act, signed into law by Richard Nixon in 1971, two years after the US put a man on the moon. The Act increased funding, and resulted in a major increase in chemotherapy research.
Mukherjee captures the excitement and pioneering spirit of this early drug war on cancer and something of the personalities of the principal protagonists. They had a sense of mission, and insofar as they had a base motivation, it was ego, not money.
They made a major contribution, and by a process of careful methodical clinical trials, often involving hundreds or even thousands of patients, many childhood cancers and several uncommon types of adult cancer became routinely curable.
Disappointingly, there was far less progress in the treatment of the more common adult cancers, and by the mid-1980s, some commentators were pointing out that the strategy in the war on cancer was misguided, and was producing disappointing, marginal returns.
In particular, the apparent emphasis on large expensive chemotherapy trials was deemed premature when basic biologists were only starting to unlock the fundamental mysteries of the cancer cell.
Those of us (I joined up as a foot soldier in the campaign in 1984) who were involved in cancer care and in the study of new drugs at this time, hoped that the scientists would soon give us rationally designed targeted drugs, better tools than the inelegant chemical weapons derivatives with which we waged the war on cancer.
Meanwhile, we would do our best with what we had, devising more extreme ways of administering chemotherapy in an attempt to improve on its marginal effectiveness. The section in the book which deals with high-dose chemotherapy, a once-promising but highly toxic approach which was undone by research fraud, is particularly illustrative.
The discovery that cancer was the result of a process of genetic mutations and alterations was fundamental to progress, and explained the weak impact of chemotherapy on most cancers. Soon novel molecularly targeted and largely non-toxic treatments for leukaemia, breast and bowel cancers, which were aimed at counteracting the effects of these genetic errors, were replacing or augmenting our poisons.
The account of the development of one such drug, herceptin, by Dr Dennis Slamon, a frequent visitor to our shores and mentor to many of our young scientists, reads like an adventure story.
I must admit that I had mixed feelings when I read the book. It is unambiguously, unreservedly a triumph of medical writing. I recommend it to anyone with an interest in medicine, science, public policy or indeed history.
Why the mixed feelings? I wish I had written it.
John Crown is the Thomas Baldwin Professor of Translational Cancer Research at Dublin City University, and is Newman Clinical Research Professor at University College Dublin. He is a candidate for the Seanad on the NUI panel
