In Pursuit of the Gene

280 ¨ EPILOGUE
vinced that X-ray crystallography would provide the key to the gene, Watson
managed to transfer to the Cavendish Laboratory in Cambridge, where
X-rays were used to study the three-dimensional structures of proteins.
Almost immediately after arriving in England, Watson met Francis
Crick, with whom he felt an instant rapport. Crick was quickly won over
by Watson’s enthusiasm for genes, and the two teamed up to solve the
structure of DNA. Watson brought Crick his knowledge of the gene and of
bacteriophage, which had replaced the fruit fly as the experimental organism
of choice for geneticists, and Crick in turn provided a keen mathematical
mind combined with a working knowledge of the basic tools of X-ray
crystallography, many of which had been developed at the Cavendish Laboratory.
Meanwhile in March 1951 at Caltech, Pauling announced that he had
solved the structure of the alpha helix, a common structural feature of
proteins, largely by means of model building. Convinced that Pauling would
next turn his attention to DNA, Watson and Crick decided to try to beat
him at his own game by building a model of DNA. Providentially, Maurice
Wilkins, whose X-ray pictures of DNA had so impressed Watson, was in
close contact with Crick and had kept him abreast of the latest developments
on the X-ray structure of DNA. Based in part on a new series of Xray
photos collected by Rosalind Franklin, who had recently come to work
at King’s College, Wilkins was now firmly convinced that DNA was a helix
consisting of at least two or more central chains. 7 While Pauling’s model
was constructed from amino acid subunits, Watson and Crick’s would be
made from the four nucleotide building blocks—each consisting of a sugar
molecule, a phosphate, and one of four differing bases, adenine, thymine,
cytosine, or guanine—that were the constituents of DNA. From the work
of Cambridge chemist Alexander Todd, they knew that the nucleotides
were linked together in a chain by their sugar-phosphate groups. Watson
and Crick’s operating assumption was that this sugar-phosphate backbone
was very regular, which accounted for the regularity seen in the X-ray pictures,
but that the order of the bases would be irregular, the differences in
the order of the bases explaining the differences between genes. 8 This principle,
that the differences among genes would be accounted for by a change
in the pattern of the subunits, was first enunciated by Muller in 1937.