Figure 24.1 X-ray diffraction images of the B form of DNA, showing the X-shaped pattern characteristic of a helical molecule. Left: Photograph 51. Right: Wilkins’s photograph of ‘orientated’ squid sperm.
This was the picture that Franklin indexed as ‘Photograph 51’. It became one of the iconic scientific images of the twentieth century and created a moment of high drama in James Watson’s Double Helix. However, Wilkins’s account of what happened to it was unsensational. He did nothing immediately, intending to wait until after Franklin had gone. A few days later, he recalled, Watson visited King’s, and Wilkins stopped him in the corridor and showed him the photograph. He did not record Watson’s reaction but noted that he ‘seemed to be in a hurry to leave’. Wilkins remembered saying that he thought that Chargaff’s base ratios were the key to the structure of DNA, and Watson replied ‘So do I’ as he dashed off.
Franklin’s farewell seminar on 28 January was ‘exceptionally long’ – an hour and three-quarters. She and Gosling had clearly put in a vast amount of effort, but Wilkins thought that ‘it did not add up’. She stuck religiously to the brief that Randall had given her – the A form, and nothing else – and talked at length about delving through the entrails of Patterson analyses to find the structures that made it crystalline. They had built a scale model in perspex of the supposed ‘unit cell’ of the crystal structure – ‘big enough to sit in’, as Wilkins said – but had no clear idea how the DNA molecules were packed into it, or what they looked like. The word ‘helix’ was not mentioned, and Photograph 51 never appeared on the screen. Afterwards, Wilkins asked her about the helical form that stood out in some of her photographs. That was the B form, she replied, and it was a helix; this one, the A form, was not. Taken aback by her sudden retreat from her ‘anti-helical’ position, Wilkins sat down and said no more.
Behind the closed door, Franklin and Gosling had finished studying the effects of water on DNA structure, which took them from their damp A form to the wet B that should have been Wilkins’s property. Now that she had extracted everything she needed from Photograph 51, she was happy to let Wilkins have it. It was a nice geste d’adieu- even if she could not bear to hand it to him herself.
After Franklin’s farewell seminar – and still with no indication of when she would actually go – Wilkins wrote a depressed note to Crick. ‘Rosie’s colloquium made me a bit sicker,’ he complained. ‘God knows what will become of all this business.’ He said he would scribble down what he could remember and pass it on. Wilkins also thanked Crick for the ‘almost daily shoal of letters’ asking him to stay in Portugal Place. At last, he could accept the invitation and looked forward, just as in the old days, to ‘a jolly, light-hearted weekend of sociability.’ He was to be cruelly disappointed.
Those waiting for him at the Cricks’ house were not Francis and Odile, but Watson and Crick. They began by handing him a typed manuscript and asking if he could see what was wrong with it. The manuscript was by Linus Pauling and Robert B. Corey of Caltech and reported their structure for DNA. This should have been a bombshell but Crick and Watson were upbeat and smug, obviously convinced that it was fatally flawed. Wilkins quickly scanned the structure – three intertwined helical strands with the phosphates innermost, just like the doomed Crick-Watson model of a year earlier – and then noticed that the chemical composition contained no sodium, which was always associated with DNA. He pointed this out and Crick exclaimed ‘Exactly!’, as though Wilkins ‘had shown special insight . . . like a schoolboy at an oral exam who happens to guess right’. This left Wilkins feeling patronised. Then Crick and Watson got down to the real reason they had summoned him to Cambridge.
Pauling was sitting pretty in Pasadena, certain that he had cracked the structure of DNA and still oblivious of the surprisingly basic blunders in his model. Crick and Watson had gained privileged access to the manuscript because Pauling had sent a copy to his son Peter, sharing their office in the Cavendish. The paper was soon to be published in the Proceedings of the National Academy of Science – when all the errors would stand revealed and an embarrassed Pauling would quickly be back in the race.
This left Crick and Watson just a few weeks to solve the structure and beat Pauling, so they wanted Wilkins to let them start building DNA models again. During the year-long moratorium, King’s had done nothing useful with DNA: no papers published, not even a consensus over whether or not it was a helix – and no models built with the templates which Crick and Watson had generously donated. Now, even Bragg wanted the Cavendish to pick up DNA again. Pauling had also sent him a copy of his paper ‘out of courtesy’, and Sir Lawrence was determined to avoid a repetition of his humiliation over the alpha-helix.
Wilkins was floored by their ‘horrible’ request and the prospect of a ‘London-Cambridge Rat Race’. He wrote later that ‘science had to march on’ and that he had ‘no alternative but to accept their position’. The promise of the ‘jolly’ weekend with the Cricks had evaporated. Disillusioned and angry, Wilkins got up to leave. Crick had ‘the sense not to press me to stay’ but Watson followed Wilkins out into the street and ‘expressed his regrets’. Wilkins was ‘not very receptive’, and went straight to the station.
Also-ran
John Randall heard about Pauling’s DNA model before Bragg, but without knowing any details of the structure. In early January 1953, he received a letter that Pauling had sent on the same day he posted his manuscript off to PNAS. Pauling first apologised for being too busy to attend a meeting that Randall was organising, and then added a coda that smelled of smugness and revenge – and reminded Randall of his refusal to share Wilkins’s DNA photographs. ‘Professor Corey and I are especially happy during this holiday season . . . we have discovered a structure of DNA which we have submitted for publication.’ He admitted that ‘our X-ray photographs are not especially good . . . but good enough to permit the derivation of our structure’.
Watson later wrote that Pauling’s ‘unbeatable combination of a prodigious mind and an infectious grin’ left many of his colleagues waiting quietly for ‘the day when he would fall flat on his face by botching something important’. Although Pauling did not know it, that day was fast approaching. His triumphant DNA structure was not just bad, it was dreadful. As well as the inside-out misplacing of the backbone and the absence of sodium which Wilkins had spotted, Pauling had invented hitherto unknown properties for the phosphate groups that supposedly made up the core. According to the laws of chemistry (which Pauling had helped to formulate), the molecule would not be acidic (despite there being a clue in the name, ‘deoxyribonucleic nucleic acid’), and the three strands could not be held together (one critic later said that Pauling’s structure would ‘explode’).
How could the brilliant Pauling, with his vast knowledge of chemistry, have made such elementary blunders? Wilkins later described his efforts as ‘pretty lamentable’ and suggested that ‘he just didn’t try’. Pauling was also the victim of his own furious drive to win yet another race, and in the process cut corners to a degree that causes ideas travelling too fast to skid out of control. For now, though, while his paper was incubating in press at PNAS, Pauling’s reputation was intact. And Watson and Crick were not going to spoil his peace by telling him where he had gone wrong.
Even before it was published, Pauling’s absurd model had important consequences. It whipped Watson and Crick into a frenzy, completed their transformation from collaborators with King’s into competitors, and drove a wedge between them and Maurice Wilkins.
This left them in a perilous situation. To build a new model, they needed hard data – molecular dimensions, angles, distances. Both men had done experiments with X-ray crystallography – Crick with proteins, and Watson with TMV – but they had no hands-on experience with DNA, which was a much greater challenge. Until now, all their structural information about DNA was second-hand, and almost exclusively filched from King’s. Crick had joked about their ‘burglary’ of results from Wilkins, Franklin and G
osling, but the ‘people at King’s’ saw no humour in their behaviour. And now they had estranged Wilkins, their only conduit of intelligence from King’s. Realistically, King’s would remain their sole source of inside knowledge about DNA. So how could they now get their hands on it?
This prompts us to revisit the day in February 1953, already described by Wilkins in rather bland terms (page 328), when Watson called into King’s and saw for himself the unmistakable ‘helical cross’ in Photograph 51. Watson’s story is radically different.
He had gone to London to see a friend at the Hammersmith Hospital, and had taken a copy of Pauling’s manuscript, which at that stage had only been seen by the inner circle at the Cavendish. On the way home, he diverted to King’s, intending to show Pauling’s paper to Wilkins. He was busy, so Watson decided to discuss it with Rosalind Franklin. He pushed into her office without knocking and found her busy measuring an X-ray photo on a light box; he noted that she was clearly not happy to be interrupted. Watson asked her if she wanted to see Pauling’s manuscript and then, rather than put her to the test as he and Crick had done with Wilkins, ‘immediately explained where Linus had gone astray’. He also pointed out that Pauling’s model, like their own, contained three strands of helical DNA. Franklin became ‘increasingly annoyed with my recurring references to helical structures’ and insisted that her own X-rays showed ‘not a shred of evidence for a helix’.
At that point, Watson ‘decided to risk a full explosion’, and ‘implied that she was incompetent in interpreting X-ray pictures’. This was the provocation that pushed her over the edge. ‘Suddenly Rosy [sic] came from behind the lab bench . . . and began moving towards me. Fearing that in her hot anger she might strike me, I grabbed up the Pauling manuscript and hastily retreated.’ At the door, he ran into Wilkins; as they walked away, Watson told him that his arrival ‘might have prevented Rosy from assaulting me’. According to Watson, Wilkins said that she had ‘made a similar lunge towards him’ following an argument some months earlier.
By Watson’s account, that shared experience ‘opened up Maurice to a degree that I had not seen before’. Wilkins told him that Franklin had been gathering evidence for a distinct structure of wet DNA that she called the ‘B form’. As this was news to him, Watson asked what the pattern looked like. Wilkins ‘went into an adjacent room’ and collected his print of Photograph 51. The effect on Watson was immediate and electric: ‘the instant I saw the picture, my mouth fell open and my pulse began to race’. Here was rock-solid evidence for a helix, and so clearly drawn that all its vital statistics could be derived.
Wilkins then took Watson for another supper in Soho. Despite a bottle of Chablis and unrelenting interrogation by Watson, Wilkins avoided revealing the exact dimensions of the helix, or how many chains he thought were intertwined, or how the bases might be brought together.
On the train home to Cambridge, Watson sketched what he could remember of the big black X on the margin of his newspaper, and tried to decide whether the structure contained three chains – still the general assumption – or only two. By the time he had cycled back to Clare College and climbed over the back gate into Memorial Court, he had made up his mind to go for two chains, and that ‘Francis would have to agree’.
On the quiet
Early March 1953, and the tempo was quickening at King’s. Unusually restless, Maurice Wilkins was feeling ‘the pressure of necessity’ and had a premonition of ‘history in the air’. The sense of urgency was heightened because he had heard nothing from Cambridge since Watson’s visit to King’s at the end of January.
Wilkins had been thinking about Chargaff’s mysterious ratios and the possible significance of A = T and C = G. He wondered whether these pairs of bases could be physically linked in the DNA molecule, and mentally sketched out a structure in which the pairs of bases lay in the same horizontal plane, as if on a tabletop, perpendicular to the long axis of the molecule. They formed the core of the structure, but he could not see how they would be tied together – and the cumbersome edifice which hovered in his imagination contained not two or three helical strands of DNA, but four.
On the practical side, he was at last mobilising his troops. Franklin’s departure was now imminent, and Randall had given his approval for a full-frontal assault on DNA. Alex Stokes rejoined the campaign, and two other crystallographers – Bill Seeds and the heavy-duty Herbert Wilson – came on board. Wilkins had found another source of top-quality DNA, which was fortunate, as he was about to discover that Franklin and Gosling had used up the last of Signer’s stock. He had visited Harriet Ephrussi-Taylor in Paris, where the photograph of Oswald Avery smiled benignly down on them from the wall of her office. Appropriately enough, Ephrussi-Taylor extracted her DNA from bacteria (E. coli as well as pneumococci) and had shown that it had the power to transform. Back at King’s, this ‘real live genetical material’ behaved as impeccably as Signer’s, yielding a beautiful ‘helical cross’ B pattern identical to that in Photograph 51.
On Saturday 7 March, Wilkins wrote to ‘My dear Francis’ – a salutation that he later admitted felt awkward. The top news – ‘I think you will be interested to know that our dark lady leaves us next week’ – meant that Wilkins was now making up for lost time. ‘Most of the three-dimensional work is already in our hands . . . the decks are clear and we can put all hands to the pumps [for] a general offensive on Nature’s secret on all fronts: models, theoretical chemistry, X-ray crystallography.’ He ended, ‘It won’t be long now . . . Yours ever, M.’
Wilkins may have hoped to subdue Crick and Watson with this display of superior firepower, especially as they could not generate any data of their own and relied on crumbs scavenged from King’s. However, his letter had the opposite effect when Crick opened it on the morning of Monday 9 March. Wilkins’s prediction that ‘it won’t be long now’ was painfully accurate, because Cambridge had already won the rat race.
In fact, Watson and Crick were already back in the running when Crick invited Wilkins up to Cambridge to extract his blessing to their resumption of model-building. On the morning of Saturday 31 January – the day after his confrontation with ‘Rosy’ and supper with Wilkins in Soho – Watson had taken his case to the top. Sir Lawrence Bragg listened to the evidence, agreed that the moratorium must end, and gave Watson permission to drop his TMV work and build models of DNA. Crick could also contribute, while finishing off his PhD on proteins.
Watson took his designs for the purine and pyrimidine templates, to be cut out of tin sheet, down to the Cavendish’s machine-room and was told that the work would take a couple of weeks; a few days more were needed because he forgot to order the phosphorus atoms. Initially, Watson worked in a dispiriting knowledge vacuum. ‘No fresh facts came to chase away the stale taste of last winter’s debacle’ – their disastrous inside-out model of December 1951 that had provoked Bragg’s moratorium. Watson complained that ‘Francis and I remained closed off from the experimental data’. An alternative interpretation is that they had ridden roughshod over a former friend and collaborator and had severed their links with the only place on the planet capable of generating the information that they needed to move on.
Fortunately for them, that embargo was soon broken, with the gift of a crucial nugget that Franklin and Gosling had dug out during their months of Patterson analyses on the A form. This was a string of numbers describing the ‘space group’ which gave the A form its crystalline appearance, together with its crystallographic designation, ‘C2’. This meant nothing to Watson, and despite her years of experience, Franklin also missed its significance. But Crick had met ‘C2’ before, deep in the structure of horse haemoglobin, and knew that it could represent a structure containing two chains that ran in opposite directions. This was powerful evidence that DNA consists of two strands, and the ‘anti-parallel’ configuration (one strand running ‘up’ and the other ‘down’) later proved essential in understanding how DNA works.
This breakthrough fired up Watson
and Crick with new energy for their attack on the two-chain model of DNA. As this took shape, it could be ‘checked directly with Rosy’s precise measurements’. Watson later admitted that ‘Rosy, of course, did not directly give us the data . . . For that matter, no one at King’s realised they were in our hands.’ Max Perutz had come to their rescue. As a member of the MRC Biophysics Committee, he had been on the annual site visit to King’s back in December and had just received his copy of the progress report, which included Franklin’s calculations on the A structure. Perutz saw nothing wrong in handing the report over to Watson and Crick.
Even though Franklin had explained at length why the phosphate-sugar backbones could only be on the outside of the DNA structure, Watson began by putting them at the heart of his new two-strand model. He persisted for some days (breaking off periodically to play tennis), even though the results ‘looked stereochemically even more unsatisfactory’ than their previous effort. Then, over supper in the Cricks’ basement dining room, Crick suggested putting the phosphates outermost; the next morning, while contemplating a ‘particularly repulsive backbone-centred model’, Watson at last picked up Franklin’s cue.
He constructed a short section of two helical backbones of phosphate-sugar, like one turn of a spiral staircase but with all the steps missing. There was a void up the middle because the machine-shop had still not delivered the tin-plate cutouts of the bases. That void could be filled with a spiral stack of steps consisting of pairs of bases, one attached to each backbone, but there was an obvious problem. The overall shape of DNA had to be a smooth cylinder, but because the two-ringed purines (A and G) were larger than the single-ringed pyrimidines (C and T), the steps made of pairs of bases would have unequal widths. The backbones would have to bulge outwards to accommodate the widest steps (purine-purine), and be pulled in around the narrowest (two pyrimidines). The outline of DNA would not be cylindrical but lumpy, like a python that has swallowed rats of different sizes.
Unravelling the Double Helix Page 36
