Codebreakers: Makers of Modern Genetics

The Gerard Wyatt papers

These characteristic ratios…in nucleic acids…indicate a highly complex structure… [I]t is tempting to speculate whether DNA composition may bear some direct relation to genetic structure.

Gerard Wyatt, 'Biochemistry Journal', 1951

Gerard Wyatt (b. 1925) is a Canadian biochemist who played a small but important role in the discovery of the double helical structure of DNA.

During the late 1940s and early 1950s Gerard Wyatt studied the ratios of the four DNA bases - adenine, guanine, thymine and cytosine - in eukaryotic cells. His observation that in DNA there is always the same amount of adenine as thymine, and the same amount of cytosine as guanine, was critical to the idea, eventually developed by James Watson, that pairs of bases were somehow linked in the DNA structure.

Erwin Chargaff at Columbia University independently made the same observation, often called 'Chargaff ratios' or 'Chargaff's rules'. However, Wyatt was thought by some to use better techniques; he also confirmed the presence of 5-methylcytosine in the DNAs of some organisms, which revised the ratios in those species to bring them nearer to 1. His work is cited both in Watson and Crick's 1953 'Nature' paper and in Watson's 1968 book, 'The Double Helix'.

In 1951 Alfred Marshak published a paper saying that some forms of phage (a virus that infects bacteria) had no cytosine in their DNA. Working with Seymour Cohen, who was part of the phage group at Cold Spring Harbor headed by Max Delbrück, Wyatt showed that these phages contained 5-hydroxymethylcytosine and guanine in equal proportion. This work removed a potential obstacle to the double helix model of DNA.

Wyatt's papers include correspondence with Cohen on this topic, a discussion that prompts speculation about 'what might have been' if they had pursued the significance of their observations for the DNA structure. Chargaff was even more reluctant to commit himself to an explanation of the ratios based on the structure.

The Wyatt papers also include reprints of his key publications (DNA, nucleic acids) between 1950 and 1953, and correspondence relating to them.

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This material is held by the Wellcome Library where originals may be consulted.

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Gerard Wyatt was born in the USA in 1925, and from 1935 settled in Canada. From 1947 to 1950 he was a research student in biochemistry at the Molteno Institute in Cambridge, England. Influenced by the Cambridge biochemist Roy Markham, he undertook to analyse the quantities of the four bases in DNA as his PhD research.

Early studies had suggested that the four bases were equally represented. Wyatt's analyses, using paper chromatography, indicated that there were equal amounts of A and T, and of G and C, but that some species were richer in the A-T component, while others were richer in G-C. He also identified 5-methylcytosine as a component of eukaryotic DNAs, correcting for erroneously low measurements of cytosine in previous studies.

While Chargaff was wary of speculation about what these observations meant, Wyatt in 1952 wrote:

One is tempted to speculate that the regular structural association of nucleotides of adenine with those of thymine and those of guanine with those of cytosine…in the DNA molecule requires that they be equal in number.

Returning to Canada, Wyatt took a post at the Canadian government Laboratory of Insect Pathology in Sault-Ste Marie. There he began the collaboration with Seymour Cohen at Cold Spring Harbor that led to the discovery of 5-hydroxymethylcytosine in phages T2, T4 and T6, previously declared to have no cytosine.

Wyatt did not follow up his DNA research in his career, and has concentrated since on the biochemistry of insects.

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