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Authors: Matthew Cobb
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physician called Colin MacLeod joined the Rockefeller Institute Hospital, attached to the pneumonia service. When Avery returned from his sick leave, the pair began investigating the chemical nature of the transforming principle. A little more than a year later, Avery explained to his new colleague Rollin Hotchkiss where he thought their study might be going. Hotchkiss recalled:
Avery outlined to me that the transforming agent could hardly be carbohydrate, did not match very well with protein and wistfully suggested that it might be a nucleic acid.
5
There were no clear results to back up Avery’s hunch, as MacLeod’s work had not been conclusive. This caused a problem – the young Canadian needed to strengthen his curriculum vitae with some published articles, so he worked instead on the effectiveness of the new sulphonamide antibiotics. The Avery group did no further research on transformation until 1940.
Despite the fact that the method for separating the transforming principle from bacterial cells had been published, no scientists took up the challenge. This was not because people did not know about or appreciate the significance of pneumococcal transformation. In 1941, the leading evolutionary geneticist Theodosius Dobzhansky published the second edition of his influential book
Genetics and the Origin of Species.
In a chapter entitled ‘Gene mutation’, Dobzhansky described the work of Griffith and Avery and claimed that their findings were ‘not unduly surprising from the standpoint of genetics’, as the change from the R to the S form could be understood in terms of a mutation. More challenging was Griffith and Avery’s demonstration that transformation could take place through contact with a killed sample – Dobzhansky reassured his readers that this ‘extravagant’ finding was ‘conclusively proved’. 6 Dobzhansky emphasised that the transformed strains did not merely acquire ‘a temporary polysaccharide envelope of a kind different from that which their ancestors have had, but are able to synthesize the new polysaccharide indefinitely.’ Dobzhansky’s conclusion was that contact with the transforming principle had somehow induced a mutation in the R bacteria, and that this could lead to the use of targeted mutation to study gene function:
If this transformation is described as a genetic mutation – and it is difficult to avoid so describing it – we are dealing with authentic cases of induction of specific mutations by specific treatments – a feat which geneticists have vainly tried to accomplish in higher organisms … geneticists may profit by devising experiments along the lines suggested by the results of the pneumococcus studies.
7
Dobzhansky was not claiming that the transforming principle was a gene, but the attention he paid to it showed that Avery’s research was widely known and was seen as important.
*
In October 1940, MacLeod and Avery returned to the problem of identifying the nature of the transforming principle. To help with their analyses, they needed a powerful ultracentrifuge that could separate bacterial contents from the rearing medium – as the sample was spun round at high speeds, the heavier molecules sank to the bottom more quickly, concentrating compounds with a similar weight into a narrow band. The Rockefeller Institute had built some of these devices, using a design developed by the Swedish scientist Theodor ‘The’ Svedberg. 8 Avery’s everyday needs were not so demanding – initially his group simply needed to obtain large quantities of bacteria. The solution was to adapt a kitchen cream separator made by the Sharples company. The Sharples, as it was called in the lab, consisted of a tube that was the size of a thick cucumber – about 5 cm in diameter and 25 cm long. There was one problem: the tube was not tightly sealed, and tiny gaps in the apparatus meant that every time it was used, the room became full of an invisible aerosol of potentially lethal
Avery outlined to me that the transforming agent could hardly be carbohydrate, did not match very well with protein and wistfully suggested that it might be a nucleic acid.
5
There were no clear results to back up Avery’s hunch, as MacLeod’s work had not been conclusive. This caused a problem – the young Canadian needed to strengthen his curriculum vitae with some published articles, so he worked instead on the effectiveness of the new sulphonamide antibiotics. The Avery group did no further research on transformation until 1940.
Despite the fact that the method for separating the transforming principle from bacterial cells had been published, no scientists took up the challenge. This was not because people did not know about or appreciate the significance of pneumococcal transformation. In 1941, the leading evolutionary geneticist Theodosius Dobzhansky published the second edition of his influential book
Genetics and the Origin of Species.
In a chapter entitled ‘Gene mutation’, Dobzhansky described the work of Griffith and Avery and claimed that their findings were ‘not unduly surprising from the standpoint of genetics’, as the change from the R to the S form could be understood in terms of a mutation. More challenging was Griffith and Avery’s demonstration that transformation could take place through contact with a killed sample – Dobzhansky reassured his readers that this ‘extravagant’ finding was ‘conclusively proved’. 6 Dobzhansky emphasised that the transformed strains did not merely acquire ‘a temporary polysaccharide envelope of a kind different from that which their ancestors have had, but are able to synthesize the new polysaccharide indefinitely.’ Dobzhansky’s conclusion was that contact with the transforming principle had somehow induced a mutation in the R bacteria, and that this could lead to the use of targeted mutation to study gene function:
If this transformation is described as a genetic mutation – and it is difficult to avoid so describing it – we are dealing with authentic cases of induction of specific mutations by specific treatments – a feat which geneticists have vainly tried to accomplish in higher organisms … geneticists may profit by devising experiments along the lines suggested by the results of the pneumococcus studies.
7
Dobzhansky was not claiming that the transforming principle was a gene, but the attention he paid to it showed that Avery’s research was widely known and was seen as important.
*
In October 1940, MacLeod and Avery returned to the problem of identifying the nature of the transforming principle. To help with their analyses, they needed a powerful ultracentrifuge that could separate bacterial contents from the rearing medium – as the sample was spun round at high speeds, the heavier molecules sank to the bottom more quickly, concentrating compounds with a similar weight into a narrow band. The Rockefeller Institute had built some of these devices, using a design developed by the Swedish scientist Theodor ‘The’ Svedberg. 8 Avery’s everyday needs were not so demanding – initially his group simply needed to obtain large quantities of bacteria. The solution was to adapt a kitchen cream separator made by the Sharples company. The Sharples, as it was called in the lab, consisted of a tube that was the size of a thick cucumber – about 5 cm in diameter and 25 cm long. There was one problem: the tube was not tightly sealed, and tiny gaps in the apparatus meant that every time it was used, the room became full of an invisible aerosol of potentially lethal
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