Life's Greatest Secret (17 page)

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At the end of 1952, Pauling finally stirred. Even though he still assumed that proteins explained genetic specificity, Pauling had been snuffling around DNA for some time – a year earlier he had cheekily written to Randall asking to see their data; Randall had given him the brush-off.
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In Watson’s mind, Pauling had become a bogeyman, a powerful competitor who had the ability to steal the prize, should he so desire. At the end of the year, just as Watson feared, Pauling submitted an article to the US journal
Proceedings of the National Academy of Sciences,
based entirely on measurements from Astbury and Bell’s data from 1938.
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But when the manuscript arrived in Cambridge at the end of January, Watson and Crick were relieved to see that the structure was just as wrong as their own first attempt. It, too, was composed of three intertwined helices; it, too, had the bases on the outside; and to their amazement the way in which the model was built meant that the molecule was not an acid at all. As Watson later put it, ‘a giant had forgotten elementary college chemistry’. Finally, the model did not explain the nature of the gene or its essential functions: replication and specificity. It was biologically mute.

A few days after reading Pauling’s manuscript, Watson went to King’s, where he had a brief squabble with Franklin over her apparent refusal to accept that DNA was helical. He then saw Wilkins, who took him to his office and showed him a photo of the B form that Raymond Gosling had given him a few days earlier as the pair worked on Gosling’s thesis; with Franklin’s departure imminent, Gosling was once again being supervised by Wilkins. This photo – ‘photo 51’– had been taken in May 1952 by Gosling, but it had not been studied and had lain in a drawer for months.
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Watson was stunned – the image was so much simpler than any he had previously seen. As he put it: ‘The instant I saw the picture my mouth fell open and my pulse began to race.’
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In the centre was an X shape; Watson was a crystallographic novice, but from his discussions with Crick, who had been working on the crystallographic interpretation of helical molecular structures, he knew that the X could only come from a helix.

The significance of photo 51 in the identification of the double helix structure of DNA has often been overstated, mainly because of the weight given to it in Watson’s own world-famous account,
The Double Helix.
In reality, the insight given by the photo was extremely limited. Everyone at King’s – even Franklin – now accepted that the B form was helical, and without any more precise details of the measurements of the molecule, all that happened was that Watson’s preconception was confirmed – DNA had a helical structure. Furthermore, there was nothing underhand going on – Watson was shown the photo in perfectly legitimate circumstances. Raymond Gosling was absolutely certain: ‘Maurice had a perfect right to that information’, he said later. Whether Wilkins used that information wisely is another matter. He later regretted his action – ‘I had been rather foolish to show it to Jim’, he wrote in his memoirs.
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Despite the excitement that Watson felt, all the main issues, such as the number of strands and above all the precise chemical organisation of the molecule, remained a mystery – a glance at photo 51 could not shed any light on those details. The decisive information, which was unwittingly provided by Franklin herself, came from another source.

Pauling’s foray into DNA structure led Bragg to lift his injunction against Watson and Crick working on a model of DNA – he was not going to allow Pauling to repeat the coup of the keratin α-helix. Wilkins reluctantly agreed. There followed a rapidly evolving frenzy of dead ends, brilliant insights and chance encounters as Watson and Crick worked furiously to solve the problem. Most decisively, Max Perutz showed Crick the MRC report that included Franklin’s brief summary of her data from fifteen months earlier. Although it contained nothing that Watson should not have noted in November 1951, it now provided Crick with the information he needed. By chance it chimed completely with what he had been working on for months: the type of monoclinic unit cell found in DNA was also present in the horse haemoglobin he had been studying. This meant that DNA was in two parts, each matching the other. As Crick later recalled, ‘the chains must come in pairs rather than three in a molecule, and one must run up and the other down.’
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Then another occupant of the Watson and Crick office, Jerry Donohue, pointed out that Watson was using the wrong forms of the bases when he was trying to build the model. With the correct structures, adenine bound with thymine, and cytosine bound with guanine, using hydrogen bonds, as Gulland had reported six years earlier.

Back at King’s, Bruce Fraser, like Watson and Crick and Pauling before him, was struggling with a triple helix structure, but this time with the bases on the inside. The model led nowhere. Meanwhile, Rosalind Franklin was finishing up her work on DNA before leaving the lab, groping her way towards a solution, oblivious to what was happening in Cambridge. The progress she made on her own, increasingly isolated and without the benefit of anyone to exchange ideas with, was simply remarkable. In January 1953 she struggled with the data from the Patterson function and complained in her notebook that she could not ‘reconcile nucleotide sequence with Chargaff’s analysis’: her data suggested a cumbersome seven-nucleotide unit that gave approximate 1:1 ratios of purines and pyrimidines, but nothing as precise as some of Chargaff’s data.
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But by 24 February, she had realised that both the A and the B forms of DNA were double helices. She also suggested that the bases on either strand were interchangeable (A with T, C with G), and above all she realised that ‘an infinite variety of nucleotide sequences would be possible to explain the biological specificity of DNA’.
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Franklin was almost there, but she did not have a chance to get any further, because Watson and Crick had already crossed the finishing line.

By the end of February 1953, Watson and Crick had agreed the basic outline of the double helix model, but this was merely a seductive concept. It needed to be turned into precise numbers, spatial relationships and chemical bonds, in the shape of a physical model. It took a week of calculation and intense work before the double helix, with complementary base pairing between A and T and between C and G, finally emerged from a tangle of precise metal templates held together by clamps. It was a molecular model informed by experimental data; it did not simply emerge from the diffraction data, as Franklin had wanted. On 7 March, Wilkins wrote to Crick announcing that the ‘dark lady’ (Franklin) was leaving King’s the following week, that ‘much of the 3 dimensional data is in our hands’ and promising to launch a ‘general offensive on Nature’s secret strongholds on all fronts’, signing off with ‘It won’t be long now’. When Crick opened the letter on 12 March, the double helix model stood in front of him.
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3. Double helix model of DNA from Watson and Crick (1953a)

Wilkins and Franklin came to Cambridge to see the model, and immediately agreed it must be right. Although Watson described Wilkins as being remarkably magnanimous at being scooped, Wilkins recalled that he felt ‘rather stunned’ and bitter and that he made ‘an angry outburst’.
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Whatever the case, it was agreed that the model would be published solely as the work of Watson and Crick, while the supporting data, without which the model would not have existed, would be published by Wilkins and Franklin – separately, of course. The first public announcement of the discovery was made by Sir Lawrence Bragg in April, at a conference in Solvay, Belgium. Pauling, who had seen the model in Cambridge and given it his blessing, told the audience that the Watson and Crick model was ‘very likely’ to be ‘essentially correct’, and that his triple helix was mistaken.
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On 25 April there was a party at King’s when the three articles were published in
Nature.
Franklin did not attend. She was now at Birkbeck and had stopped working on DNA.

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Franklin was never told the full extent to which Watson and Crick had relied on her data to make their model; if she suspected, she did not express any bitterness or frustration. In subsequent years she became very friendly with Crick and his wife, but she was never close to Wilkins or Watson, although she interacted with Watson as she worked on the structure of the tobacco mosaic virus.
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Franklin died of ovarian cancer in 1958, four years before the Nobel Prize was awarded to Watson, Crick and Wilkins for their work on DNA structure.

In 1968 Jim Watson published
The Double Helix,
in which he gave a gripping but partial account of events and a frank description of his own bad behaviour, particularly with regard to Franklin. The epilogue to the book contains a generous and fair description of Franklin’s vital contribution and a recognition of his own failures.
The Double Helix
also suggested that Max Perutz had given Watson and Crick a confidential document when he handed over the MRC report containing those vital paragraphs by Franklin. Perutz was hurt by this allegation and showed that it was not true. There can be no doubt that the data in the report provided Crick with the insight he needed to come up with the correct structure, but the document was not confidential, and above all Franklin had publicly communicated the essential results nearly eighteen months earlier. Watson had been in the audience, but he had not understood the significance of what was being said.
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One of the main facts that in retrospect seems so obvious, but which was not at the time, is the role of what are sometimes called the ‘Chargaff rules’ – the fact that the amounts of A and T and of C and G are equivalent. These ratios were not known to be so precise at the time and they were certainly not ‘rules’. As Jerry Donohue, who shared Watson and Crick’s room at the Cavendish laboratory, later recalled in somewhat exaggerated fashion:

When the final model of DNA was discovered – more or less by accident – it wasn’t Chargaff’s rules that made the model, but the model that made the rules.

The Watson and Crick paper in
Nature
concluded coyly, ‘It has not escaped our notice that the pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.’
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This was the solution that Watson had been searching for – the complementary pairing of the bases gave a potential insight into gene duplication; with a single molecule it was possible to create two identical daughter molecules, simply by copying each strand using complementary pairing. Even more significant was what the three
Nature
papers did not say – none made any reference to how genes functioned, or the significance of the sequence of bases. There was still no genetic code.

* The rap contest can be seen at http://www.youtube.com/watch?v=35FwmiPE9tI.

–     SEVEN     –

On 19 March 1953, about two weeks after the double helix model had been completed, Francis Crick wrote a letter to his 12-year-old son, Michael, who was at boarding school. Crick told Michael what he had discovered, and included a sketch of the structure of DNA. He then went on to explain the significance of the double helix:

It is like a code. If you are given one set of letters you can write down the others. Now we believe that the D.N.A. is a code. That is, the order of the bases (the letters) makes one gene different from another gene (just as one page of print is different from another).

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Although the idea that the sequence of bases might be the source of genetic specificity had been in the air for some time, this was the first time that anyone had said that DNA contains a code, and Crick’s son Michael was the first to read it. In 2013 the letter was sold at auction for $6m.

Crick went even further in the second paper he published in
Nature
with Watson, which appeared on 30 May 1953. Like their first publication, this article contained no data at all – it was purely theoretical. As the title explained, its aim was to explore the ‘genetical implications of the structure of deoxyribonucleic acid’.
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The article began by suggesting that DNA was ‘the carrier of a part of (if not all) the genetic specificity of the chromosomes and thus of the gene itself’. This ‘big picture’ was absent from all three DNA papers published in April, which dealt solely with the structural chemistry of the molecule, not its function, with the exception of the coy closing phrase ‘it has not escaped our notice …’. Much of Watson and Crick’s second article was devoted to expanding on that cheeky insight. They described how, during gene duplication, the double helix could unwind, with each chain forming the template for the construction of a new molecule, leading to the creation of two identical daughter double helices.
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