Francis Crick

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Francis Crick : biography

8 June 1916 – 28 July 2004

One of the few references cited by Watson and Crick when they published their model of DNA was to a published article that included Sven Furberg’s DNA model that had the bases on the inside. Thus, the Watson and Crick model was not the first "bases in" model to be proposed. Furberg’s results had also provided the correct orientation of the DNA sugars with respect to the bases. During their model building, Crick and Watson learned that an antiparallel orientation of the two nucleotide chain backbones worked best to orient the base pairs in the centre of a double helix. Crick’s access to Franklin’s progress report of late 1952 is what made Crick confident that DNA was a double helix with antiparallel chains, but there were other chains of reasoning and sources of information that also led to these conclusions.In chapter 3 of The Eighth Day of Creation, Horace Judson describes the development of Watson’s and Crick’s thinking about the structure of DNA and how it evolved during their model building. Watson and Crick were open to the idea of tentatively ignoring all individual experimental results, in case they might be wrong or misleading. Judson describes how Watson spent a large amount of time ignoring Crick’s belief (based on Franklin’s determination of the space group) that the two backbone strands were antiparallel. On page 176, Judson quotes a letter written by Watson, "The model has been derived almost entirely from stereochemical considerations with the only X-ray consideration being the spacing between the pair of bases 3.4 A which was originally found by Astbury."

As a result of leaving King’s College for another institution, Franklin was asked by John Randall to give up her work on DNA. When it became clear to Wilkins and the supervisors of Watson and Crick that Franklin was going to the new job, and that Linus Pauling was working on the structure of DNA, they were willing to share Franklin’s data with Watson and Crick, in the hope that they could find a good model of DNA before Pauling was able. Franklin’s X-ray diffraction data for DNA and her systematic analysis of DNA’s structural features was useful to Watson and Crick in guiding them towards a correct molecular model. The key problem for Watson and Crick, which could not be resolved by the data from King’s College, was to guess how the nucleotide bases pack into the core of the DNA double helix.

Another key to finding the correct structure of DNA was the so-called Chargaff ratios, experimentally determined ratios of the nucleotide subunits of DNA: the amount of guanine is equal to cytosine and the amount of adenine is equal to thymine. A visit by Erwin Chargaff to England in 1952 reinforced the salience of this important fact for Watson and Crick.Personal communication: Conversation between Francis Crick and Kim Booth, August 1980 The significance of these ratios for the structure of DNA were not recognized until Watson, persisting in building structural models, realized that A:T and C:G pairs are structurally similar. In particular, the length of each base pair is the same. Chargaff had also pointed out to Watson that, in the aqueous, saline environment of the cell, the predominant tautomers of the pyrimidine (C and T) bases would be the amine and keto configurations of cytosine and thymine, rather than the imino and enol forms that Crick and Watson had assumed. They consulted Jerry Donohue who confirmed the most likely structures of the nucleotide bases.See Chapter 3 of The Eighth Day of Creation: Makers of the Revolution in Biology by Horace Freeland Judson published by Cold Spring Harbor Laboratory Press (1996) ISBN 0-87969-478-5. Judson also lists the publications of W. T. Astbury that described his early X-ray diffraction results for DNA. The base pairs are held together by hydrogen bonds, the same non-covalent interaction that stabilize the protein α-helix. The correct structures were essential for the positioning of the hydrogen bonds. These insights led Watson to deduce the true biological relationships of the A:T and C:G pairs. After the discovery of the hydrogen bonded A:T and C:G pairs, Watson and Crick soon had their anti-parallel, double helical model of DNA, with the hydrogen bonds at the core of the helix providing a way to "unzip" the two complementary strands for easy replication: the last key requirement for a likely model of the genetic molecule. As important as Crick’s contributions to the discovery of the double helical DNA model were, he stated that without the chance to collaborate with Watson, he would not have found the structure by himself.Page 75 of What Mad Pursuit by Francis Crick. "If Jim had been killed by a tennis ball, I am reasonably sure I would not have solved the structure alone".