The Mysterious World of the Human Genome. Frank Ryan

the two, only Wilkins ever seems to have made any attempt at compromising. He asked other colleagues what he should do, but Alexander (Alec) Stokes, his closest colleague, was even meeker than he was. In Brenda Maddox’s opinion, the two should have got on well; Wilkins was gentle in manner and, despite his lack of self-confidence, was attractive to women. He was mathematically fluent and immersed in the very problems that concerned Franklin. But ‘confrontation’, in Maddox’s words, ‘was Franklin’s tactic, whenever cornered’. In an earlier confrontation with her professor, R. G. W. Norrish, when working on a postgraduate research project at Cambridge, she would confide, ‘When I stood up to him … we had a first-class row … he has made me despise him so completely I shall be quite impervious to anything he may say in the future. He gave me an immense feeling of superiority in his presence.’

      Sayre, who championed her friend, would admit that Franklin’s ogrish depiction of her professor was unkind and inaccurate. Professor Norrish was awarded the Nobel Prize in Chemistry in 1967.

      Sayre had a correspondence with Norrish in which she described Franklin as ‘highly intelligent … and eager to make her way in scientific research’, but also ‘stubborn, difficult to supervise’ and, perhaps most tellingly, ‘not easy to collaborate with’. In Maddox’s opinion, ‘If Rosalind had wished, she could have twisted Wilkins around her little finger.’ The fact is she had no wish to collaborate with him. This left Wilkins isolated locally so instead he turned to Crick and Watson at Cambridge. It also meant that Franklin was equally isolated. To the commonsensical Crick, this may have been a crucial factor when it came to working out the molecular structure of DNA. ‘Our advantage was that we had evolved … fruitful methods of collaboration, something that was quite missing in the London group.’

      In that same year of Franklin’s appointment, just before Wilkins headed for America, he asked his colleague, Alec Stokes – another Cambridge-educated physicist – if he could work out what kind of diffraction pattern a helical molecule of DNA would project onto an X-ray plate. It took Stokes just twenty-four hours to do the mathematics, largely figuring it out while travelling home on the commuter train to Welwyn Garden City. A helical model fitted very closely with the picture Gosling and Wilkins had obtained in their diffraction pictures of DNA. It would appear that if anybody first confirmed that DNA had a helical structure, the credits must surely include Wilkins, Gosling and Stokes – the latter would subsequently lament that, in retrospect, he might have merited 1/5000th of a Nobel Prize.

      In November 1951, Wilkins told Watson and Crick that he now had convincing evidence that DNA had a helical structure. Watson had only recently heard Franklin say something similar in a talk about her research during a King’s College research meeting. This inspired Watson and Crick to attempt their first tentative three-dimensional model for DNA.

      But where to begin?

      Taking their cue from Linus Pauling, Watson and Crick decided that they would attempt to construct a three-dimensional physical model of the atoms and molecules that made up DNA with their covalent and hydrogen bond linkages to one another. On the face of it, the structure was made up of a very limited number of different molecules. There were the four nucleotides – guanine, adenine, cytosine and thymine – but they also knew that the structure contained a sugar molecule, deoxyribose, and a phosphate molecule. The phosphate was likely to be playing a structural role, perhaps holding the thread together, much as phosphate is a key structural component of our bony human spine. In the colloquium at King’s, attended by Watson, such was his lackadaisical absence of focus that he completely missed the importance of Franklin’s statement that the phosphate-sugar ‘spines’ were on the outside, with the coding nucleotides, the GACT, on the inside. As usual, he had eschewed making notes. All that seemed to intrigue Watson was the fact that the King’s people were uninterested in the model-building approach developed, with such aplomb, by Pauling.

      In 1952 Franklin appears to have undergone a drastic change of heart in her own thoughts on the structure of DNA. She had in her possession a brilliantly clear X-ray picture of DNA, taken by Gosling, that clearly showed a helical structure to the molecule. She called this her ‘wet form’, and also her ‘B form’. But she had even clearer pictures of a different structure of the same molecule in its ‘dry form’, or ‘A form’, that did not appear to suggest a helix. The contrast between the two forms caused Franklin to dither as to whether the DNA molecule was helical. There is a suggestion that she may have asked the opinion of an experienced French colleague, who advised her to place her bets on whichever form gave the clearest pictures. She must have been altogether aware of the advice her ignored colleague, Wilkins, would have given. Unfortunately, she ended up putting the B form into a drawer, meanwhile focusing most of her research over that year into the A form.

      Early that same year Watson and Crick made a first attempt at building a triple-stranded helical model of DNA, with a central phosphate-sugar spine. When Wilkins brought Franklin and Gosling up to Cambridge to view the model, they broke out into laughter. The model was absolute rubbish. It did not fit at all with the X-ray diffraction predictions. Thanks to Watson’s lackadaisical focus, and his failure to take notes at Franklin’s colloquium, he had made the cardinal error of putting the phosphate-sugar spine at the dead centre of their helix and not on the outside, as Franklin and Gosling had clearly deduced.

      Sayre, who rightly defended Franklin from the egregious caricature depicted by Watson’s book, loses track of the contribution of Wilkins and Gosling. It is true that Franklin and Gosling had produced some of the clearest pictures yet of the B form of DNA, pictures of such clarity that they did come astonishingly close to the truth of its molecular structure. But then, confused for a year by the two seemingly different patterns of the A and B forms, Franklin veered away from her own earlier conclusions and for a year she took the view that DNA wasn’t helical at all. Sayre appears to refute this, but Gosling would subsequently confirm Wilkins’ account of how, on Friday 18 July 1952, Franklin goaded Wilkins with an invitation to a wake. The invitation card announced, with regret, the death of the DNA helix (crystalline) following a protracted illness. ‘It was hoped that Dr M. H. F. Wilkins would speak in memory of the deceased.’ At the time Wilkins assumed it was typical of Gosling’s sense of humour. But many years later he would discover that it was Franklin who had written the card, and it confirmed her refutation of any helical structure of DNA in that confused year.