I962 M. H. F. WI LKI N S 



nucleotide chains was complex and the base composition of different DNA's 

 varied considerably, the numbers of adenine and thymine groups were always 

 equal, and so were the numbers of guanine and cytosine. In the electron 

 microscope, DNA was seen as a uniform unbranched thread of diameter 

 about 20 A. Signer, Caspersson, and Hammarsten 7 showed by flow-bire- 

 fringence measurements that the bases in DNA lay with their planes roughly 

 perpendicular to the length of the thread-like molecule. Their ultraviolet 

 dichroism measurements gave the same results and showed marked par- 

 allelism of the bases in the DNA in heads of spermatozoa. Earlier, Schmidt 8 

 and Pattri 9 had studied optically the remarkable ordering of the genetic 

 material in sperm heads. Astbury 10 made pioneer X-ray diffraction studies 

 of DNA fibres and found evidence of considerable regularity in DNA; he 

 correctly interpreted the strong 3.4 A reflection as being due to planar bases 

 stacked on each other. The electro-titrometric study by Gulland and Jordan 11 

 showed that the bases were hydrogen-bonded together, and indeed Gulland 12 

 suggested that the polynucleotide chains might be linked by these hydrogen 

 bonds to form multi-chain micelles. 



Thus the remarkable conclusion that a pure chemical substance was in- 

 vested with a deeply significant biological activity coincided with a consid- 

 erable growth of many-sided knowledge of the nature of the substance. 

 Meanwhile we began to obtain detailed X-ray diffraction data from DNA. 

 This was the only type of data that could provide an adequate description 

 of the 3-dimensional configuration of the molecule. 



The Need for Combining X-ray Diffraction Studies of DNA with Molecular 



Model-Building 



As soon as good diffraction patterns were obtained from fibres of DNA, 

 great interest was aroused. In our laboratory, Alex Stokes provided a theory 

 of diffraction from helical DNA. Rosalind Franklin (who died some years 

 later at the peak of her career) made very valuable contributions to the X-ray 

 analysis. In Cambridge, at the Medical Research Council laboratory where 

 structures of biological macromolecules were studied, my friends Francis 

 Crick and Jim Watson were deeply interested in DNA structure. Watson 

 was a biologist who had gone to Cambridge to study molecular structure. 

 He had worked on bacteriophage reproduction and was keenly aware of 

 the great possibilities that might be opened up by finding the molecular 



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