Richard Doll: Science Will Always Win in the End
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Masterpiece Richard Doll: Science will always win in the end ➜ Interview by Anna Wagstaff In 1950, Richard Doll showed the world that smoking causes lung cancer. Today, aged 92, a word from him can still cause anxiety in the Nokia boardroom or have us counting our por- tions of fruit and veg. He carries the responsibility lightly, because he believes in the power of evidence. After all, when it comes to the causality of cancer, he wrote the rules. Lung cancer had been rising sharply for Was yours the first epidemiological decades before your groundbreaking study on lung cancer? report showed, with only a one in a RICHARD DOLL There were a few others, but we million scintilla of doubt, that smoking is were the first to have sufficient confidence in a cause of lung cancer. Why did such a our findings to state that “We conclude that strong association take so long to identify? smoking is a cause and an important cause of RICHARD DOLL Cigarette smoke had first been the disease.” suspected in the 1920s, but some pathologists A couple of very primitive studies had been tried to produce skin cancer in mice by smear- carried out in Germany, but they were very ing them with cigarette smoke tar. When there flawed. For example, one used the average age of was no response, smoking was ruled out as a lung cancer patients as a basis for selecting con- possible carcinogen, and researchers turned trol patients – so if the average age of the lung their attention to other possible causes. cancer patients was 54, they interviewed a lot of The technique of testing for carcinogens by people aged 54. You really need to have the sep- exposing animals to them had only been intro- arate experiences of a 70-year-old and a 30-year- duced in about 1919, in Japan, and for the next old, you can’t assume that the experience of a two or three decades, scientists thought that's 54-year-old is representative. the way we discover the causes of cancers, by Then there was a US study that came out getting suspect materials and putting them on about the same time as ours and had similar the skin of mice. findings, but because they had used less rigor- I myself did not expect to find smoking was ous techniques, they were more cautious about a major problem. If I’d had to bet money at that drawing conclusions from their data, and mere- time, I would have put it on something to do ly concluded that there was an association with the roads and motorcars. they’d found which might imply causality. 28 I CANCER WORLD I DECEMBER 2004 Masterpiece With Richard Peto, who became known in the cancer world as the man behind the Oxford Early Breast Cancer Collaborative Group, which first proved the benefits of adjuvant therapy. Doll brought Peto with him to Oxford when he took up his post as Regius Professor of Medicine at the University in 1969 I CANCER WORLD I DECEMBER 2004 29 Masterpiece I did not expect to find smoking was a major problem… I would have bet on roads and motorcars The trouble was that, until then, epidemiology versa. So where people didn’t smoke there had been concerned almost entirely with shouldn’t be much lung cancer. And that’s what infectious diseases, which required very we found when we looked round the world. different methods and tended to look at differences between entire populations – Was the medical world convinced? differences in rainfall, temperature, things like RICHARD DOLL Not at all. Sir Harold that. With cancer and chronic diseases, you Himsworth, the Secretary of the Medical need to compare individuals with the disease Research Council (MRC), who had commis- against those without. There are all sorts of sioned the study, accepted the results straight biases that can affect this kind of off. But most cancer research workers did not epidemiological study, and that was not accept it, and in fact they advised the understood at the time. A person being Department of Health that they shouldn’t take interviewed, for instance, will tend to any action because they were uncertain about overemphasise something that they think might what it meant. be useful. It took some time to establish and It wasn’t until 1957, when the Government find techniques to eliminate all the biases that asked the MRC for a formal opinion as to can affect the results. whether our conclusion was correct or not, that We were confident of our data because we the MRC formally considered it and said it was had taken steps to ensure that our results were correct and advised the Government to that robust. Chance you could cut out immediately, effect. The result was that the Minister of because you were talking about odds of less Health in 1957 called a press conference to than one in a million of getting our results by announce the results of the MRC consultation. chance. Then you had to show that your results He announced that the MRC had advised them weren’t biased, and then you had to show that that smoking was the cause of the great increase the results were not due to what is now called in lung cancer. While he was reporting this to confounding; that it was not smoking that the media, he was smoking a cigarette himself! caused the disease, but smoking was associated One of the problems we found in trying to with something else that did. For example lung convince the scientific community was that cancer is associated with drinking alcohol – thinking at that time was dominated by the dis- smokers tend to drink more alcohol. covery of bacteria such as diphtheria, typhoid, Then we checked our results against and the tubercle, which had been the basis for ecological evidence, to see what sense it made the big advances in medicine in the last decades in the world at large. If smoking is the cause, of the 19th century. we ought to find that wherever the disease was When it came to drawing conclusions from common, smoking should be common, and vice an epidemiology study, scientists tended to use While the minister announced that smoking caused lung cancer, he was smoking himself 30 I CANCER WORLD I DECEMBER 2004 Masterpiece designed another one, using a different method. We decided to look at people’s smoking habits and see whether that could predict who would contract lung cancer. We chose doctors as our sample, principally because they were easy to follow up, and we planned to do the study for five years. But with- in two and a half years, we already had 37 deaths from lung cancer – none in non-smokers, and a high incidence in heavy smokers. The associa- tion was very clear. It turned out to have been very fortunate to have chosen doctors, from a number of points of view. One was that the medical profession in this country became con- vinced of the findings quicker than anywhere else. They said, “Goodness! Smoking kills the rules that had been used to show that a par- doctors, it must be very serious,” and, ticular germ was the cause of an infectious dis- of course, a very high proportion gave up. ease – Koch’s three postulates. Koch was a great After five years we had around 70 cases, but German pathologist who discovered the tuber- by this time, our results were beginning to show cle bacillus, and one of his postulates was that that smoking was also associated with a number you must always find the organism in every case of other diseases, particularly with heart disease, of the disease. so we decided to continue the study, though this When we did our study on lung cancer and had never been the initial plan. smoking, 50 years later, a number of scientists thought this applied to the cause of chronic dis- Your findings have implications for us eases. A lot of people said, “Smoking can’t be the all. Do you get drawn in to discussions cause of lung cancer because I have seen a case about people’s lifestyles? in a non-smoker, and therefore by Koch’s postu- RICHARD DOLL My job has been to try to find late smoking is not the cause.” out what the causes are, or what is the efficient But, of course, nobody was saying it was the treatment. If I then go round telling people what cause; what we were saying is that it is a cause. they should do, I may get prejudiced because People didn’t realise that these chronic diseases I’m committed to a particular opinion, and as a could have multiple causes. And smoking is only scientist you must always be prepared to change one cause of lung cancer – it happens to be your mind if the evidence changes. much the most important cause, however. I am now committed to the viewpoint that people shouldn’t smoke, but that’s 50 years after How did you convince the doubters? the first observation. I never gave any advice for RICHARD DOLL When we saw that, apart from the first 30 years. But it is so established now Sir Harold Himsworth and one or two others, that there is no question of my being prejudiced. practically no-one believed our conclusions, we People can also over-react. Radiation is an thought it’s no good repeating the study. So we example – people are ridiculously frightened of They said: Goodness! Smoking kills doctors, it must be very serious I CANCER WORLD I DECEMBER 2004 31 Masterpiece Tobacco bosses in 1950 were horrified by the idea that what they were selling was killing people it.