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Modern Genetic Analysis Chapter 2. The Structure of Genes and Genomes The Nature of DNA
Genetics In Process2-2: James Watson and Francis Crick propose the correct structure for DNA

A 1953 paper by James Watson and Francis Crick in the journal Nature began with two sentences that ushered in a new age of biology: "We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest." The structure of DNA had been a subject of intense debate since 1944 when Avery et al. showed that DNA is the hereditary substance. Although the general composition of DNA was known, it was not known how all the parts fit together. The structure must fulfill the two main requirements for a hereditary molecule, the ability to store information and the ability to replicate.

Watson (an American phage geneticist) was a visitor in the Cavendish laboratory in Cambridge, England, when he began his collaboration with Crick, an English physicist. Their DNA model was based on the evidence about structure available at the time. Maurice Wilkins and Rosalind Franklin had obtained X-ray diffraction patterns of DNA that suggested it had a helical structure. Erwin Chargaff had analyzed many different DNAs and devised several empirical rules concerning the four constituent bases, of which the most significant was that the amount of adenine (A) equals the amount of thymine (T), and guanine (G) equals cytosine (C).

From this information Watson and Crick pieced together a structure that seemed to fit the data. The structure they proposed was a double helix of two nucleotide chains running in opposite directions. The two chains were bound to each other by the pairing of specific bases, A with T, and G with C. This accounted satisfactorily for the equality of A with T and of G with C shown by Chargaff. Eventually they tested their ideas by building a scale model of DNA out of metal. Watson later described the excitement of assembling the model in the following words:

I wandered down to see if the shop could be speeded up to produce the purines and pyrimidines later that afternoon. Only a little encouragement was needed to get the final soldering accomplished in the next couple of hours. The brightly shining metal plates were then immediately used to make a model in which for the first time all the DNA components were present. In about an hour I had arranged the atoms in positions which satisfied both the X-ray data and the laws of stereochemistry. The resulting helix was right-handed with the two chains running in opposite direction. Only one person can easily play with a model, and so Francis did not try to check my work until I backed away and said that I thought everything fitted. While one interatomic contact was slightly shorter than optimal, it was not out of line with several published values, and I was not disturbed. Another fifteen minutes' fiddling by Francis failed to find anything wrong, though for brief intervals my stomach felt uneasy when I saw him frowning. In each case he became satisfied and moved on to verify that another interatomic contact was reasonable. Everything thus looked very good when we went back to have supper.

The double helix fulfilled the requirements for a hereditary substance: the nucleotide sequence could code for amino acid sequence in protein, and replication was possible by strand separation and new synthesis directed by the specificity of the base pairing.

© 1999 by W. H. Freeman and Company. All rights reserved.