Unravelling the Double Helix

by Gareth Williams

  It was at this point that Wilkins had come to Cambridge, naively believing that this would be a weekend of bonhomie and gastronomy with Francis and Odile. After their discussion turned sour, Watson followed Wilkins out into the street to apologise, but his later account of the visit does not show much remorse. ‘Maurice’s slow answer emerged as no, he wouldn’t mind our building models . . . Even if his answer had been yes, our model-building would have gone ahead.’

  And so Watson continued, interrupted by tennis, popsies, sherry parties and a trip to the local fleapit to see the heavily censored Ecstasy. There were still no templates from the machine-room, so Watson copied out the structures of the bases from Norman Davidson’s benchtop bible, The Biochemistry of the Nucleic Acids, and cut their shapes out of stiff card so that he could try to fit them together on his desk. Somehow, he and Crick had forgotten about John Griffith’s prediction that specific pairs of bases could be pulled together by hydrogen bonding. Now, Watson thought about hydrogen bonding again and, as Crick had done, first wondered whether each base could attract itself. He spent an excited night awake ‘with pairs of adenine residues whirling in front of my closed eyes’, only for that notion to be ‘torn to shreds’ the next morning by Jerry Donohue, the American crystallographer who now shared their office.

  It was Donohue who gave Watson the crucial nudge which finally set him off down the short but thrilling home straight to the winning post. Each of the bases exists in two chemical forms, thanks to a hydrogen atom which can dodge from one position on the molecule to another; this switch instantly changes the anchor-points for hydrogen bonding. Watson had copied out the bases’ structures from Davidson’s book, which showed an odd selection of the two forms. Donohue’s winning tip was to use just one version – the ‘keto’ form – which according to recent research was the one that occurred in real life. Watson spent the afternoon redrawing the keto versions of the bases and fiddling with his card cutouts, but the bolt of inspiration did not hit him until he had slept on it all.

  First thing the next morning, Saturday 28 February 1953, Watson cleared a space on his desk for his card cutouts and began sliding the shapes around. This unleashed not just a eureka moment, but a string of them.

  ‘Suddenly, I became aware that an adenine-thymine pair held together by two hydrogen bonds was identical in shape to a guanine-cytosine pair.’ The hydrogen bonds lined up naturally, ‘with no fudging required’ (Figure 24.2). Instantly, Chargaff’s rules – A = T, C= G – made perfect sense, and a mechanism to explain how DNA replicated itself sprang into his mind. ‘It was thus very easy to visualise how a single chain could be the template for the synthesis of a chain with a complementary sequence.’

  As soon as Jerry Donohue arrived, Watson made him check the structures; he found ‘no objection’ and Watson’s spirits ‘skyrocketed’. And when Crick turned up, he only got halfway through the door before Watson ‘let loose that everything was in our hands’. They spent the morning trying to find errors in Watson’s scheme, and failed. Elated, they adjourned to the pub for lunch. Watson later wrote that he felt ‘slightly queasy’ when ‘Francis winged into the Eagle to tell everyone within hearing distance that we had found the secret of life’.

  Figure 24.2 Hydrogen bonding (dotted lines) linking adenine with thymine and cytosine with guanine, to bridge the two helical strands of DNA. It was later realised that there are three hydrogen bonds between cytosine and guanine.

  Crick’s recollection of these momentous events diverges in places from Watson’s. The revelation about base-pairing was, according to Crick, a simultaneous and shared experience: ‘Jerry and Jim were by the blackboard and I was by my desk, and we suddenly thought, well perhaps we could explain the 1:1 ratios by pairing the bases . . . At that point, all three of us were in possession of the idea . . . It was the next day that Jim came in and did it.’

  And sadly, Crick had ‘no recollection’ of that glorious moment when he supposedly informed the lunchtime drinkers in the Eagle that they had solved the mystery of life. He did, however, remember telling Odile that they had made a ‘big discovery’, but as he was forever saying things like that, she thought nothing of it.

  Bragg was in bed with flu when he heard the news but was ‘immediately enthusiastic’ and instantly became ‘one of our strongest supporters’. The machine-room was slower to respond. The metal base templates were not delivered until the first week of March. Four days of frantic but painstaking work on the model followed, building-block by building-block, and then checking the position of each atom. When they finished on the morning of Saturday 7 March, Crick ‘just went straight home and to bed’.

  They were back in the lab on the morning of Monday 9 March. Their model was standing on the bench top in Crick’s line of sight as he opened the letter from Maurice Wilkins which began ‘My dear Francis’ and went on to tell him that ‘the dark lady’ was leaving and that ‘It won’t be long now’. Neither Crick nor Watson had the heart to break the news to Wilkins, so they asked someone else to do it.

  Scooped

  On Thursday 12 March, John Kendrew rang Maurice Wilkins and invited him up to the Cavendish to see the new Watson-Crick model of DNA. Kendrew revealed little – two strands, held together by hydrogen bonds between pairs of bases – but Wilkins instantly felt ‘tension in the air’ and was ‘on a train to Cambridge straight away’.

  The model was almost six feet high, even though it only represented a single turn of the double helix (Figure 24.3). Gazing up at it, Wilkins saw some familiar features – the helical backbones of sugar-phosphate spiralling vertically and placed outermost, with the bases lying horizontally in the core of the structure. There were also some alien touches – only two strands of DNA, not three, and a stroke of pure brilliance in the construction of the steps in the spiral staircase. All the steps were identical in width, because an adenine joined to a thymine by hydrogen bonds is precisely the same length as a cytosine linked to a guanine. This meant that the two backbones spiralled evenly around each other, always the same distance apart.

  Figure 24.3 Jim Watson and Francis Crick with their model of the double helix, April 1953.

  Watson watched Wilkins, lost in thought, while Crick talked non-stop about the unique features of the double helix. Watson had feared some sort of backlash because, as he put it, ‘we had seized part of the glory which should have gone in full to Wilkins and his younger colleagues’. But, according to Watson, Wilkins looked at the model and then went back to London ‘with not a hint of bitterness’. Either Watson or his memory edited out an unpleasant exchange that Wilkins later described as ‘an angry outburst’. This came when Crick and Watson asked Wilkins, still contemplating the double helix, if he wanted to be the third author on the paper which they were writing for Nature about their structure.

  Until that moment, Wilkins had been ‘rather stunned’ by the model, which to him seemed to say, ‘I know I am right.’ Their question about co-authorship brought him back to earth with a nasty bump. He realised how ‘possessive’ he felt about DNA and the ‘deeply satisfying times’ it had given him – and also how much of the model was derived from ‘work done at King’s’. Instead of thanking them for their offer, Wilkins made clear his bitterness, which Crick told him was ‘unfair’. The untouchable question of who had done what was still hanging in the air when Wilkins left to return to London.

  At King’s the next day, Wilkins told ‘everybody’. There was general dismay and anger that Crick and Watson had got there first, especially as they had done none of the experiments themselves. Ray Gosling was ‘quite upset at being scooped’, while Randall was as furious as ‘a scalded cat’. After the weekend, Gosling took the news to Rosalind Franklin, who had finally packed her trunk and said goodbye to the circus, and was settling in on her first day at Birkbeck. She reacted with equanimity: ‘We all stand on the shoulders of others.’ And then, even though Randall had barred her from working on DNA or with Gosling after leaving King’s, she and Goslin
g sat down to revise a manuscript which had been in preparation for the last month.

  They had finished their big paper on the influence of the water content of DNA in mid-February. On 23 February, Franklin’s lab book shows that she had dug out her own copy of Photograph 51. This was forbidden fruit, because Randall had allocated the B form to Wilkins, but she now began to analyse it in detail. She quickly concluded that it was indeed helical – and decided, from the new data, that it must consist of two strands, not three. From her lab book entries, it is clear that she was convinced that Chargaff’s base ratios were significant, but she stopped short of spotting that a purine would pair up with a pyrimidine – the revelation that could have led her to the double helix ahead of Watson and Crick.

  But now, armed with the information about the model that Wilkins had brought back from Cambridge, she could check to see whether it fitted the Patterson analyses that she and Gosling had laboured over for months. She and Gosling set to work.

  On Wednesday 18 March, Wilkins received a copy of the draft paper from Francis Crick. He read it carefully, then sat down and dashed off a reply. ‘I think you’re a pair of old rogues,’ he wrote, ‘but you may well have something. I like the idea.’ Wilkins made a watered-down reference to his ‘angry outburst’ in front of the model. ‘I was a bit peeved because I was convinced that the 1:1 purine pyrimidine ratio was significant and as I was back on helical schemes I might, given a little time, have got it.’ Philosophically, he added, ‘But there is no point grousing. It’s a very exciting notion and who the hell got it isn’t what matters.’ Nonetheless, King’s deserved recognition for all that they had done. ‘We would like to publish a brief note with a picture showing the general helical case alongside your model. I can have the whole thing ready in a few days.’

  At that point, Wilkins broke off, only to return to the letter a short while later. ‘Just heard this moment of a new entrant to the helical rat-race.’ Franklin and Gosling had contacted him because they had already written a paper, or as Wilkins put it, ‘served up a rehash of our ideas of 12 months ago’. His ill-feeling against Franklin had apparently evaporated. ‘It seems that they should publish something (they have it all written). So at least three short articles in Nature. Christ!’ He signed off, ‘As one rat to another, good racing. M.’

  Things moved very rapidly through the end of that week, at various levels. Up in the stratosphere, civilised words were exchanged over lunch in the Athenaeum between John Randall and the joint editors of Nature, Jack Brimble and Arthur Gale, and a gentlemen’s accommodation was swiftly reached. King’s would be given a few days’ grace to write up their two papers, and all three would appear as a job lot in Nature on 25 April 1953.

  Meanwhile, down on the shopfloor, there was a frenzy of writing and rewriting. On Monday 23 March, Wilkins scribbled a note to Crick, complaining that he was ‘so browned off with the whole madhouse that I don’t really care much about what happens’. His paper, co-written with Alex Stokes and Herbert Wilson, was ready to be sent to Nature. So was ‘Rosie’s thing’ – an alternative analysis of the B form (Wilkins hoped that the editors would not ‘spot the duplication’) which, as Gosling later said, showed ‘to our great satisfaction and delight’ that it fitted beautifully with a two-chain helical structure.

  King’s won the last-minute scramble to finish and send off the papers. On Thursday 26 March, Wilkins wrote an elated postcard to Crick: ‘You will be relieved (I am) to hear that all is safe in the hands of Gale.’ This was despite ‘a frantic rush at the last moment: no typist and two missing figures which after a long search turned up in Randall’s bag and in Rosie’s room’.

  Typists were also in absentia at the Cavendish a couple of days later, although by then it was Saturday afternoon. Watson’s sister Elizabeth, visiting Cambridge en route to Paris and Tokyo, was pressed into service on the pretext that her role was crucial to ‘the most important event in biology since Darwin’s book’. Even with Crick and Watson standing over her, the manuscript did not take long to type, as it was barely 900 words long; it was accompanied by an elegant figure of the double helix, drawn by Odile Crick.

  The paper was checked by Bragg the following Tuesday 31 March, and sent off to Nature first thing the next morning, April Fool’s Day. A visiting dignitary from the Rockefeller captured the ‘great air of excitement’ in the Cavendish, with the ‘young and somewhat mad hatters’ and their ‘huge model’, which had come out of ‘the beautiful X-ray diagrams produced in Randall’s lab, and some of the work in Cambridge’.

  In early April, two visitors called into Cambridge to inspect the Watson-Crick double helix. The first was Linus Pauling, on his way to a conference in Brussels. There was no sign of his usual cocky showmanship; on arrival in Brussels, he wrote home to his wife and ended his letter reflectively, ‘I think that our structure is probably wrong, and theirs probably right.’ The second visitor was Rosalind Franklin. Watson was surprised to see how ‘gracefully’ she agreed that the double helix must be right. It was as though the dramatic confrontation in King’s which Watson described in such graphic detail had never happened.

  Soon after the Watson-Crick paper was dispatched to Nature, Watson ignored Crick’s protestations that they still had work to do and went to Paris with his sister. Elizabeth’s destination was Japan, to marry ‘an American she had known in college’. Brother and sister had always been close, and these were their last few days together in ‘the carefree spirit that had marked our escape from the Middle West’. Watson bought her an expensive umbrella in Faubourg St Honoré, as a wedding present. Just before she flew on, they celebrated Watson’s birthday on 6 April. It was his twenty-fifth, and by his own assessment, he was now ‘too old to be unusual’.

  Print run

  As is usual for Nature, the issue of 25 April 1953 covered a broad base, including the virus that caused ‘trashy leaf’ in tobacco plants, glucose uptake in the gut, radium on the ocean floor and – of interest to Rosalind Franklin in her previous life – a form of carbon that chewed its way into the brickwork of blast-furnaces. But the undisputed centrepiece that week was a trilogy of papers about the structure of DNA.

  The third in the pecking order was by Franklin and Gosling, from the MRC Biophysics Unit at King’s (an asterisk beside Franklin’s name indicated that her present workplace was Birkbeck College). Their article consisted of two pages of heavyweight mathematical analyses of the B form; discussion of the A form was deferred to another paper in press. The B form was illustrated by Photograph 51, which showed ‘in striking manner the features of helical structures first worked out in this laboratory by Stokes’. They were careful to point out that ‘Stokes and Wilkins were the first to propose such structures for nucleic acid fibres, although a helical structure had previously been suggested by Furberg’. The Patterson analyses had led them to conclude that DNA was ‘probably helical’, containing two co-axial chains with the phosphate groups lying outermost and the bases inside. This was ‘not inconsistent with the model proposed by Watson and Crick’. They ended, ‘We are grateful to Professor J.T. Randall for his interest, and to Drs F.H.C. Crick, A.R. Stokes and M.H.F. Wilkins for discussion.’

  Wilkins, Stokes and Wilson reached much the same verdict through a different mathematical pathway, the Bessel derivation which Stokes had worked out on the train home and never published. Their theoretical prediction of an X-shaped diffraction pattern was best seen in ‘the exceptional photograph obtained by our colleagues RE Franklin and RG Gosling’, shown in the accompanying paper. The structure of DNA had moved on from Astbury’s pile of pennies, to ‘a spiral staircase with the core removed’, and there appeared to be ‘reasonable agreement with the kind of model described by Watson and Crick’. Crucially, the basic structure of DNA was identical in a wide range of species – mammals, fish, wheat, bacteria and even a bacteriophage virus – and the fact that live spermatozoa showed the same X-ray pattern strongly suggested that this was the form of DNA which occurred in vivo. A
t the end, Wilkins et al thanked ‘our colleagues, R.E. Franklin and R.G. Gosling; and Dr J.D. Watson and Mr F.H.C. Crick for stimulation’.

  And so to the paper which eclipsed the other two; the one that everybody knows about even if they have never read it. Compared with the others, it was short and sweet: a paragon of clarity and conciseness that contains two of the most famous sentences in the scientific literature of the twentieth century. The first was its carefully understated opening, ‘We wish to suggest a structure for DNA. This structure has novel features which are of considerable biological interest.’ Watson and Crick began by demolishing Pauling’s three-stranded model, and also the ‘rather ill-defined’ structure by Bruce Fraser which preceded it. Their own vision was ‘radically different’: two helical chains winding around the same axis, the phosphate-sugar backbones outermost and the bases stacked horizontally up the core. The ‘novel feature’ was ‘the manner in which the two chains are held together by hydrogen bonding between specific pairs of purine and pyrimidine bases’, namely A with T and C with G. This tallied with experimental measurements of bases in DNA, but they did not mention Chargaff by name. The double helix was ‘roughly compatible’ with previously published information and, significantly, with the ‘more exact results’ in the two accompanying papers. Watson and Crick stated that ‘We were not aware of the details of the results presented there when we devised our structure, which rests mainly though not entirely on published experimental data and stereochemical arguments.’