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The dance of A, C, G and T: the Wyatt notebooks

14/03/2013

By Chris Hilton

Following the launch of Codebreakers: the makers of modern genetics online resource, we will be posting a series of blogs about the 20 digitised archive collections at its core. To get started, Dr. Chris Hilton, senior archivist at the Library introduces the Gerard Wyatt collection, which is located at the Wellcome Library.

4 DNA base pairs: A C T G

DNA base pairs: C-T and A-G. WI no. B0002547

Crick and Watson’s description of the structure of DNA is one of the “Eureka” moments known well beyond the boundaries of science; for example, in 2005 when the last major batch of Crick’s papers was delivered to the Wellcome Trust, the removal men manhandling the crates off the lorry to the loading bay were familiar with Crick and his key achievement, and excited to be playing a part in bringing his papers back to Britain. The 1953 Watson and Crick paper in Nature is known to the lay public as one of those points at which, intellectually, everything changed, and the double helix is its instantly recognisable visual signature. However, there is an argument that the helix, brilliant logo though it makes, is a less important aspect of the molecule. The key, rather, lies in its double nature: the fact that each of the four bases that make up one strand can only link to one other type. Adenine can only link to Thymine, Guanine to Cytosine, and vice versa; a particular sequence of bases on one strand thus predicts absolutely exactly the sequence on the other strand, AGCT on the one being married to TCGA on the other. In perhaps the most famous understatement in the history of science, Crick ensured that the paper announcing the structure of DNA contained the words “It has not escaped our notice that the specific pairing we have postulated immediately suggests a copying mechanism”.

The paper, of course, has to back its assertions, and it does so, inter alia, by referring to experimental data indicating that when DNA is broken down the amount of Adenine found will always match that of Thymine; similarly for Guanine and Cytosine. Footnotes point us to the source of this data.  First comes work by Erwin Chargaff, another of the key figures in the DNA story. However, there is also a reference to “Wyatt, G.R., Jour. Gen. Phys. 36. 201, (1952).” Behind this footnote lie a series of laboratory note books also held at the Wellcome Library under the reference PP/GRW: the papers of Gerard Wyatt (b.1925). Browse one of Wyatt’s digitised note books in the player:

Wyatt, an American by birth who had moved to Canada, spent the years 1947-1950 as a research student in Cambridge, working at the Molteno Institute on DNA. The quantative analysis of the molecule that he undertook in these years was the basis of his Ph.D.; it also formed the basis of several scientific papers, including the one from the Journal of General Physiology that Watson and Crick cite in Nature.  In the Wellcome Library notebooks, which Professor Wyatt presented to us in 2003, we see the ratios of the four different bases performing their elegant dance, A forever bound to T and C to G, providing the Watson and Crick proposal with hard factual underpinning. The significance of this work is that it provided a clearer picture of the ratios than Chargaff’s figures. Crick, interviewed years later by Horace Judson, made this point: “The data of Chargaff’s, you know, wasn’t all that convincing unless you wanted to believe it [...] until Wyatt came along and boosted it up” (Judson, The Eighth Day of Creation, 1979, p. 179).

Professor Wyatt’s subsequent career has been spent working on the biochemistry of insects rather than specifically on DNA (although DNA of course occurs in his work: a recent paper that he co-authored, for example, related to “A DNA-binding protein, tfp1, involved in juvenile hormone-regulated gene expression in Locusta migratoria”: Shutang Zhou, Max L Tejada, Gerard R Wyatt and Virginia K Walker, in Insect biochemistry and molecular biology 2006;36(9):726-34). All the while that he was pursuing his post-doctoral work, however, his data on the ratio of DNA bases was underpinning the work Crick, Watson and many others did to follow up the insights of the 1953 Nature paper. This is not, perhaps, a good time to quote a journalist as a guide to one’s conduct, but the principle set out by C.P. Scott, editor of the Manchester Guardian in the early 20th century, that “Comment is free, but facts are sacred” is apposite here: theory can come and go, but without experimental underpinning it is nowhere. The neat columns of figures in Wyatt’s lab notes are one of the foundations of modern genetics.

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