Book review: biography of Richard Doll

Smoking kills: the revolutionary life of Richard Doll by Conrad Keating Signal Books: Oxford, 2009 I only once had the opportunity of hearing Richard Doll speak. It was in 2004, after a hard-hitting lecture by Charles Warlow on over-regulation of research (http://tiny.cc/m1n7v). Doll, aged 92, looking physically frail but mentally alert, stood up to point out that under current ethics regulation, none of the epidemiological studies that he had done to demonstrate a link between smoking and cancer would have been possible. The only way to rescue epidemiology from the trend for increasingly strict and bureaucratic constraints, he felt, was for someone to deliberately flout the law and be prepared to go to prison for the cause of liberating research. "I am prepared to volunteer myself for that role", he said, prompting a spontaneous outburst of applause. This engaging biography of Doll paints a picture of a man who could have been trusted to follow through on this offer. But as well as telling us about the remarkable life of Doll himself, the book is fascinating for its account of the history of evidence-based research in medicine. Doll would have gone to Cambridge to read mathematics were it not for the fact that he flunked one of the examinations after being plied with strong alcohol the night before. That fateful event led him to study medicine at St Thomas's Hospital, but he never lost his love of mathematics, and was quick to see the potential for using statistical methods and randomisation to evaluate treatments. Together with Austin Bradford Hill he developed the method of randomised controlled medical trials which has become the cornerstone for evaluation of efficacy of treatments. He subsequently took up a post researching disease prevention, a niche that not only suited him well, but was also one of the few options open to him, as his membership of the Communist party made him virtually unemployable as a hospital doctor. Remarkably, Home Office regulations meant he was also banned from teaching undergraduates, although he was allowed to teach postgraduate students. The account of his seminal work on smoking and cancer was a revelation to me. I had no idea that in the 1950s it was commonplace for doctors to offer a cigarette to a patient to calm them down before an examination. Nor that there had been a six-fold increase in lung cancer mortality in males between 1930 and 1944. Many of the discussions around this epidemic are reminiscent of those currently seen in the field of autism – was there some factor that could explain the increase, or was it simply that detection of the disease had improved, especially with new X-ray methods for visualising tumours? Doll was remarkable for his single-mindedness and energy in assessing large numbers of patients, and for his ability to see the need for controls. He was ever alert to the possibility of misinterpreting data and developed methods of guarding against unwitting bias. Calculations were done by hand and painstakingly checked. Doll was concerned not to publish until certain of his facts, leading to some delay in publication of the first results. Keating emphasises the extent to which Doll felt it important not to become a campaigner for public health measures, but merely to present the results of his findings. It is a view nicely summed up by a comment attributed not to Doll, but to his collaborator Hill, who was confronted at a cocktail party by a doctor who said "You're the chap who wants us to stop smoking." "Not at all," replied Hill. "I'm interested if you go on smoking to see how you die." As each new study by Doll found further support for a strong link between smoking and lung cancer, and also revealed an unexpected link with heart disease, initial apathy towards the results turned into acceptance by the Medical Research Council, criticism by the tobacco industry, who derided the findings as 'unscientific', and alarm by the government, who made substantial sums in taxes on smoking. One of the harshest critics was the eminent statistician and heavy smoker R. A. Fisher. Fisher was exercised by a key limitation of epidemiological studies, the lack of experimental control. "Correlation does not mean causation" was his mantra, and he argued forcefully for alternative explanations of the association. The debate turned acromonious, with Fisher accusing Doll and Hill of failure to make their data available, and others accusing Fisher of conflict of interest, owing to his lucrative consultancies with tobacco companies. Again, aspects of the debate have some modern resonances: in my own field of neuropsychology, it is often argued that the goal is to find the necessary and sufficient cause of a disorder, much as Fisher had argued. On this view even a single case of lung cancer in a non-smoker could overturn a causal theory. But gradually it became clear that a factor such as smoking could act as a risk factor for disease without acting in a deterministic fashion. In my own writings on developmental neuropsychology I have used the example smoking and cancer to make the point that causal mechanisms may be multifactorial and probabilistic (http://tiny.cc/i8x5l), but until I read this book I had not realised that there was a bitter debate around this very issue in the 1950s. Keating describes it as a shift from reliance on Koch's postulates to Hill's specification of criteria for causality. Koch, working on infectious diseases had specified that, among other things, to prove an organism was the cause of a disease the organism had to be discoverable in every instance of the disease, and that experimental animals could be given the disease by inoculation with a pure culture. Hill's criteria involved nine viewpoints, none of which on its own gave indisuptable evidence for a causal effect, but which taken together would help determine whether causality was a reasonable hypothesis: strength, consistency, temporality, biological gradient, plausibility, coherence, experiment and analogy. Doll is best-known for his work on smoking, but he also played a pivotal role in discovering the health risks of asbestos, ionising radiation and the contraceptive pill. Keating tackles head-on the accusations that emerged after Doll's death that he was in the pay of companies such as ICI and Monsanto, and refutes firmly any suggestion of malpractice. Doll believed that if one wanted to obtain access to data it was important to have some relationship with companies. This emerged most strikingly in his early work on asbestos, where his preliminary findings caused shock and alarm. He resisted attempts to suppress the data, but negotiated with the company where he had done his studies with the aim of doing further analyses. The company were willing to implement changes to their working practices and Doll judged that more good could be done by working with them than attacking them: after Doll's findings, measures for containing asbestos fibres were taken so that the workers could at last see that there was a clock on the far-side wall. Doll made no personal profit from this company, nor from his work for chemical firms, whose fees were donated to charity. Nevertheless, the book raises big questions about how to handle potential conflict of interest and illustrates the importance of modern practices of full disclosure – which only became commonplace after his retirement, and of which Doll fully approved. I can thoroughly recommend this book as providing a stimulating account of a fascinating life. It puts into historical perspective aspects of medical statistics and epidemiology that are now largely taken for granted, but which may have taken much longer to be developed without Doll's intelligence and dedication. A final word of thanks to the Book House, Summertown, the small, independent bookseller where I happened upon this book. Please support them if you live in Oxford: I can guarantee that if you wander in and have a browse, you will find something interesting and unexpected on the shelves. (And no, I don't have any vested interests – just keen for the survival of a local amenity!)