1951 Cold Spring Harbor symposium was on the topic ‘Genes and mutations’, and one of the speakers was Harriett Ephrussi-Taylor, who took the opportunity to survey the seven years that had passed since Avery, MacLeod and McCarty had published their landmark paper. She was downbeat:
Considering the interest which was aroused by the publication of the results of the chemical and biochemical study of the capsular transforming agent of pneumococcus, it is surprising that so few scientists are at present working in this field.
38
As she admitted, transformation was difficult to study – for example, transformation in Boivin’s
E. coli
system ‘occurred only with some irregularity’ – and many researchers were not familiar with the pneumococcal system in which transformation had first been described. She glumly concluded that the study of transformation remained isolated: ‘as yet,’ she said, ‘no bridge can be seen leading over into classical genetics’.
Ephrussi-Taylor’s lament was related to what now appears to be an odd feature of genetics research in the second half of the 1940s – many biologists, including geneticists, simply did not ‘get’ Avery’s result. Not only did they not immediately accept that genes were made of DNA, they did not even attempt to test the hypothesis in the systems they studied. For example, Max Delbrück first heard of Avery’s breakthrough in May 1943, when his Vanderbilt colleague Roy Avery showed him the letter from New York that announced the discovery. Delbrück later recalled his ‘total shock and surprise’ at the contents of the letter, ‘which I read there standing in his office in the spring sunshine’. 39 But despite his ‘shock’, Delbrück did nothing. He did not start studying the role of DNA in viruses, nor did any of his colleagues, even though they were all intimately aware of the results that were coming out of Avery’s laboratory. Delbrück later explained that the suggestion that genes were made of DNA left them nonplussed. As he put it ‘you really did not know what to do with it’. 40 With the easy wisdom of hindsight, this lack of interest in what led to the most remarkable biological discovery of the twentieth century looks remarkably short-sighted. And at one level, it was. The phage group did not react in the way that Lederberg, Boivin and others did. Their diffident attitude was one component of the failure of Avery’s discovery to immediately transform biology. 41 Avery’s findings now look so obvious, and yet many scientists at the time responded to them with hostility or bemusement.
One of the scientists who did not immediately embrace Avery’s findings was the young Gunther Stent, who worked with Delbrück. In 1972, Stent sought to explain the lack of widespread recognition of the importance of the Avery group’s discovery by suggesting that the result was ‘premature’. 42 This term does not explain anything; in fact it obscures the historical reality of how Avery’s work was received, and it does not explain why some scientists accepted the finding but others rejected it. There were two valid criticisms of Avery’s suggestion that DNA was the hereditary material in the transforming principle, each of which gradually became weaker. First, there was the issue of potential protein contaminants, which led the Avery group to employ increasingly precise techniques, the results of which all indicated that protein contamination was not the cause of transformation. Second, there was the conundrum of how exactly specificity might be represented in what were supposed to be boring molecules – if DNA was essentially composed of four bases, a way needed to be discovered that enabled it to bring about the almost infinitely different effects produced by genes. The leading chemists of DNA such as Gulland were happy to imagine that specificity could reside in DNA through the sequence of bases, or their proportions, but this had yet to be
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