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In 1948, when I began to work with Professor Bradford Hill at the Medical Research Council's Statistical Research Unit, ideas about the causes for cancer were still dominated by those of the great German pathologists of the 19th century. A favourite idea was that cancers arose from embryonic cells that had persisted unchanged in character in adult tissues. The idea that a cancer might arise from a mutation in the hereditary material of a somatic cell had been suggested at least as early as 1930 by McCombs and McCombs1 and this, I believe, had also been suggested some 15 years before, but I forget by whom. It was not, however, widely believed, which was surprising in view of the fact that Muller's demonstration,2 as long ago as 1927, that X-rays could produce hereditary mutations in fruit flies was universally applied and its application to humans was not questioned. X-rays, however, were not thought to be able to cause cancer unless they had caused macroscopic damage to tissues.3 Even as late as 1960 it was possible for Austin Brues, a distinguished American scientist, to write a 'Critique of mutational theories of carcinogenesis'.4

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