Why Arthur Mourant Decided To Say 'No' To Ronald Fisher

[Ed. note: Thirty years ago, the eminent geneticist and statistician Ronald A. Fisher approached blood testing specialist Arthur Mourant with the idea for a joint research project. Why not use blood groups to see if smokers differed genetically from nonsmokers? Mourant was tempted for a number of reasons, not the least of which was maintaining his long and fruitful professional relationship with the famous Fisher, author of the classic textbook The Genetical Theory of Natural Selection (Oxford University Press, 1930). But the proposed study raised serious ethical questions, and after careful consideration Mourant felt compelled to decline. Now 84, Mourant lives in retirement on the island of Jersey in the English Channel He has had a distinguished career in three countries—Great Britain, France, and the United States. Although trained as a geologist, he later switched sciences and his fame rests on a rich body of original work on blood groups and their hereditary clinical, social, and geographic patterns. His books, The Distribution of the Human Blood Groups (Blackwell Scientific, 1954), has long been regarded as a pioneering work. In this story Arthur Mourant remembers the dilemma posed by his encounter with one of the great names of 20th century genetics.J During the 1930s, public health authorities in Britain realized that both the incidence of lung cancer and the mortality from this disease were increasing rapidly. But few persons at that time seem to have realized that any particular chemical carcinogen could be responsible for these observations. The possibility that smoking might be the culprit became widely recognized only in 1950, after the publication of work by epidemiologist Richard Doil and medical statistician AustinBradfordHill in Britain, and by chest surgeon Ewarts Graham and medical student Ernst Wynder in the United States. Both groups of investigators found a strong association between smoking and lung cancer when they interviewed large numbers of patients with and without the disease. Doll and Hill also put forward convincing evidence that this was a causal relationship—and that heavy cigarette smokers were 30 times more likely to die from the disease than lifelong nonsmokers. I myself became convinced of the danger of tobacco smoke and, having previously been an occasional social smoker, decided to give up the habit entirely. But that was nearly 10 years after I had come to the attention of Ronald Fisher, the professor of ge netics at Cambridge who was later knighted for his major contributions to genetics and statistics. In 1944, when I was working in the National Blood Transfusion Service, I investigated a case of severe reaction to a blood transfusion, inexplicable by contemporary dogma. I showed that it could be explained by the controversial theory of the genetics of the Rhesus blood groups, just previously published by Fisher. The geneticist recognized that my work gave important new and independent support to his theory, and invited me to apply for a vacancy that had just occurred in the Galton Laboratory Serum Unit at Cambridge, directed by Dr. Robert R Race, a close friend and colleague of Fisher. After joining the unit, I frequently met Fisher and, like Race, came to rely on his outstanding insights over the next dozen years or so into the genetic basis of my blood-group serological work. He clearly trusted me as a reliable and honest investigator and one who would be accepted as such by other scientists. A heavy pipe smoker, Fisher had a strong interest in the link between smoking and cancer. It was an interest that became an obsession of his. But he took a different view than most other competent investigators. Fisher claimed that the urge to smoke, and susceptibility to cancer, were probably separate consequences of a particular genetic constitution. In other words, smoking did not cause the disease. Instead, both the habit and the cancer resulted from a third, inborn factor. If correct, this interpretation would have meant that avoiding or giving up smoking could have no effect in reducing an individual’s chances of contracting lung cancer. Clearly, substantiation of Fisher’s belief would have been of considerable benefit to commercial tobacco interests. In 1958, after I had left Cambridge to become director of the Ministry of Health’s Blood Group Reference Laboratory, Fisher wrote to me and made a proposal for a joint research project. In his letter, Fisher argued that there had been a serious omission in previous and current work on lung cancer. No consideration had been given to the possibility “that the smoking classes are genetically differentiated, and that this is the explanation of whatever differences in cancer incidence that can be found between these classes,” he wrote. Fisher suggested that I organize a population study, aimed at detecting any association between smoking habits and hereditary blood groups. He proposed that I should arrange to test about 5,000 individuals around Britain for their blood groups and at the same time record their smoking habits. “If there were significant differences observable [in blood type] between major smoking classes such as nonsmokers and cigarette smokers,” Fisher explained, that would mean that smokers and nonsmokers were genetically different. To finance the research, Fisher said, the Tobacco Manufacturers’ Committee would be prepared to meet “all proper expenses, including remunerations, necessary to get it carried out by admittedly well-qualified and independent workers.” Although I suspected privately that Fisher’s obsession was the first sign of deterioration of an exceptionally brilliant mind, I could not reject his offer out of hand. I did have to point out—quite truthfully—that it would have been impossible at that time for such work to be conducted in my own laboratory. But I certainly considered accepting the challenge of organizing a study, which could be carried out here, perhaps in the regional centers of the National Blood Transfusion Service. It was true also, as Fisher realized, that his intended survey, quite apart from its relation to smoking, would have provided substantial new information on the distribution of blood groups in the country. This would have been of great interest and relevance to my own anthropological researches. But what of the propriety of such a piece of work? I gave the matter much thought, and indeed exchanged several more letters with Fisher. I also discussed the proposal with Race, who had by then become the world’s leading authority on blood group genetics. Race pointed out that the results from just one of the many genetically distinct blood group systems might by chance appear to support a genetic basis for smoking habits. I agreed entirely with this warning. There was a danger that, however clearly I presented my findings, financially interested organizations could interpret them wrongly to support the notion of hereditary differences between smokers and nonsmokers. Moreover, the eventual interpretation of the results— and any subsequent propaganda— would be beyond my control. At this point, a more courageous and less cautious person might have accused Fisher of self-deception, and his sponsors of bad faith. I did not feel able to do this. I did, however, decide that I could not accept personal responsibility for the survey. Clearly, it was my duty not to participate in work of this sort, which I was coming to regard as unethical. I wrote to Fisher, telling him that I would be very reluctant to conduct or organize his proposed research “for this would be a most time-consuming administrative job, and I am already spending far too much time in administration.” Fisher was deeply disappointed with my decision, and the project was never done. So ended, to my great regret, a period of most fruitful collaboration with a very great man.

Why Arthur Mourant Decided To Say 'No' To Ronald Fisher

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December 1988

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