Francis Crick : biography
It was clear that some macromolecule such as a protein was likely to be the genetic molecule.Page 32 of What Mad Pursuit by Francis Crick. However, it was well known that proteins are structural and functional macromolecules, some of which carry out enzymatic reactions of cells. In the 1940s, some evidence had been found pointing to another macromolecule, DNA, the other major component of chromosomes, as a candidate genetic molecule. In the 1944 Avery-MacLeod-McCarty experiment, Oswald Avery and his collaborators showed that a heritable phenotypic difference could be caused in bacteria by providing them with a particular DNA molecule.
However, other evidence was interpreted as suggesting that DNA was structurally uninteresting and possibly just a molecular scaffold for the apparently more interesting protein molecules.Pages 33–34 of What Mad Pursuit by Francis Crick. Crick was in the right place, in the right frame of mind, at the right time (1949), to join Max Perutz’s project at Cambridge University, and he began to work on the X-ray crystallography of proteins.Chapter 4 of What Mad Pursuit by Francis Crick. X-ray crystallography theoretically offered the opportunity to reveal the molecular structure of large molecules like proteins and DNA, but there were serious technical problems then preventing X-ray crystallography from being applicable to such large molecules.
Crick taught himself the mathematical theory of X-ray crystallography.Page 46 of What Mad Pursuit by Francis Crick. "..there was no alternative but to teach X-ray diffraction to myself." During the period of Crick’s study of X-ray diffraction, researchers in the Cambridge lab were attempting to determine the most stable helical conformation of amino acid chains in proteins (the α helix). Linus Pauling was the first to identify the 3.6 amino acids per helix turn ratio of the α helix. Crick was witness to the kinds of errors that his co-workers made in their failed attempts to make a correct molecular model of the α helix; these turned out to be important lessons that could be applied, in the future, to the helical structure of DNA. For example, he learnedPage 58 of What Mad Pursuit by Francis Crick. the importance of the structural rigidity that double bonds confer on molecular structures which is relevant both to peptide bonds in proteins and the structure of nucleotides in DNA.
1951–1953: DNA structure
In 1951, together with William Cochran and Vladimir Vand, Crick assisted in the development of a mathematical theory of X-ray diffraction by a helical molecule. This theoretical result matched well with X-ray data for proteins that contain sequences of amino acids in the Alpha helix conformation. Helical diffraction theory turned out to also be useful for understanding the structure of DNA.
Late in 1951, Crick started working with James D. Watson at Cavendish Laboratory at the University of Cambridge, England. Using "Photo 51" (the X-ray diffraction results of Rosalind Franklin and her graduate student Raymond Gosling of King’s College London, given to them by Gosling and Franklin’s colleague Maurice Wilkins), Watson and Crick together developed a model for a helical structure of DNA, which they published in 1953. For this and subsequent work they were jointly awarded the Nobel Prize in Physiology or Medicine in 1962 with Maurice Wilkins.Francis Crick’s 1962 .
When James Watson came to Cambridge, Crick was a 35-year-old graduate student (due to his work during WWII) and Watson was only 23, but he already had a Ph.D. They shared an interest in the fundamental problem of learning how genetic information might be stored in molecular form.Crick traced his interest in the physical nature of the gene back to the start of his work in biology, when he was in the Strangeways laboratory; Page 22 of What Mad Pursuit by Francis Crick.In The Eighth Day of Creation, Horace Judson describes the development of Watson’s thinking about the physical nature of genes. On page 89, Judson explains that by the time Watson came to Cambridge, he believed genes were made of DNA and he hoped that he could use X-ray diffraction data to determine the structure. Watson and Crick talked endlessly about DNA and the idea that it might be possible to guess a good molecular model of its structure. A key piece of experimentally-derived information came from X-ray diffraction images that had been obtained by Maurice Wilkins, Rosalind Franklin, and their research student, Raymond Gosling. In November 1951, Wilkins came to Cambridge and shared his data with Watson and Crick. Alexander Stokes (another expert in helical diffraction theory) and Wilkins (both at King’s College) had reached the conclusion that X-ray diffraction data for DNA indicated that the molecule had a helical structure—but Franklin vehemently disputed this conclusion. Stimulated by their discussions with Wilkins and what Watson learned by attending a talk given by Franklin about her work on DNA, Crick and Watson produced and showed off an erroneous first model of DNA. Their hurry to produce a model of DNA structure was driven in part by the knowledge that they were competing against Linus Pauling. Given Pauling’s recent success in discovering the Alpha helix, they feared that Pauling might also be the first to determine the structure of DNA.Page 90, In The Eighth Day of Creation by Horace Judson.