Unravelling the Double Helix

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Unravelling the Double Helix Page 34

by Gareth Williams


  Crick tried to defend the model; or, as Watson put it, ‘Francis prattled on’. When he stopped, Watson took over and quickly argued himself into absurdity. They all made polite conversation over lunch, and the King’s group went home on an earlier train than anticipated.

  The Crick-Watson DNA model (Mark One) had important repercussions. It hardened Franklin’s prejudice against trying to build models of molecules until the crystallographic and mathematical data were firmly nailed down; otherwise, models could be made ‘until the cows come home’ without knowing if they were anywhere near the truth.

  The fiasco also made the King’s group realise that they were in a competition which could degenerate into a race. Furthermore, their competitors in Cambridge were pushy and ambitious and were tackling DNA from a completely different perspective; they looked like rank amateurs now, but there was a risk that they might somehow get there first. Above all, Crick and Watson stood revealed as determined opportunists. It emerged later that Crick had written a memo about the model, mentioning that the concept had been ‘stimulated by the results presented to us by the workers at King’s College’. The unanimous view of those ‘workers’ was that their data had been exploited by people who had never bothered to do any of the experiments themselves.

  Maurice Wilkins was particularly hurt by that last unpalatable fact of scientific life. On 11 December, he typed a letter on headed notepaper to ‘My dear Francis’. After the friendly greeting, he got straight to the point. ‘Reluctantly and with many regrets’, he was relaying ‘the average vote of opinion here’, which was that Crick and Watson should not ‘continue to work on DNA in Cambridge’. He personally had always benefited from discussing his work with Crick, but ‘your attitude’ had left him with ‘an uneasy feeling in this respect’. Now, the freedom to exchange ideas and results was in jeopardy. He had discussed the matter with Randall, who told him to send a copy of the letter to Perutz. ‘Yours very sincerely, Maurice’ had an awkward ring to it.

  This formal letter was backed up by a handwritten note, sent the same day. It was heartfelt, and muddled. ‘This is just to say how bloody browned off I am and how rotten I feel about it all and how entirely friendly I am . . . We are really between forces which may grind us into little pieces.’ If one of those forces was Franklin, Wilkins did not mention her. However, Wilkins told Crick that he ‘had to restrain Randall from writing to Bragg to complain about your behaviour’. He advised Crick to ‘pipe down’ with Bragg, and ended with a swipe at the humiliated but presumably unbowed Watson. ‘And poor Jim – may I shed a crocodile and very confused tear?’ Wilkins signed that note off with ‘Friendly greetings to both of you, Yours, M.’

  Intimations of unhappiness at King’s, and possibly of dastardly behaviour in the Cavendish, filtered through to Bragg, who issued a decree. King’s had been working on DNA for years; henceforth, DNA would be exclusively their property. The moratorium on DNA research at Cambridge would enable Crick to resume the work he should have been doing on protein structures. Watson, having failed to make any headway with myoglobin, would instead use X-ray diffraction to investigate a plant virus, tobacco mosaic virus (TMV), which formed regular crystalline structures.

  Watson’s new project was not some random sentence handed down from on high. Some weeks earlier, the National Research Council of America had caught up with one of its more slippery overseas fellows. Watson had written to the NRC, explaining why his fellowship – awarded to learn biochemistry in Copenhagen – should be transferred for him to do X-ray diffraction at the Cavendish. His letter was so ill-judged that Salvador Luria wrote Watson a stinging rebuke in which he called him ‘a goddam bastard’. As expected, the NRC rejected Watson’s proposal, and told him they would stop his funding unless he returned to Copenhagen.

  The NRC had the support of Watson’s mother, who wrote to tell them that it was high time her son was taught a hard lesson. However, she was up against people who were prepared to perjure themselves to keep Watson at the Cavendish. His champions wrote persuasive letters, saying that he would dedicate himself to learning biochemistry while studying TMV in Cambridge. This sounded reasonable but was a lie, as Watson had every intention of staying at the Cavendish to work on X-ray crystallography. Watson must have impressed those who bent the truth on his behalf: Max Perutz, John Kendrew, Salvador Luria, Max Delbrück and even Sir Lawrence Bragg – not forgetting the wronged Herman Kalckar in Copenhagen, whose letter of support to the NRC was drafted (in good English) by James D. Watson.

  By way of a Christmas present, or a peace offering, Watson and Crick gave Wilkins their machine-shop templates for making molecular models. John Randall also attempted to bring peace to his Unit; he called Wilkins and Franklin into his office and assigned each of them to separate projects on the structure of DNA. His allocation might have reflected ignorance of who had done what, or may have had a more cynical motive. Wilkins was to focus solely on the ‘wet’ pattern, which Franklin had discovered; and Franklin would restrict herself to the crystalline ‘damp’ DNA, which Wilkins had regarded as his property. Wilkins accepted Randall’s ruling and in the spirit of the season, handed Franklin all that remained of Signer’s magical DNA.

  Rosalind Franklin did not stay in London for Christmas. She retreated to her circle of friends in Paris, where she complained bitterly about the ‘clowns’ she had to work with at King’s. She also tackled Jacques Mering directly, pleading with him to give her a place back at her beloved Labo Central.

  * This was lightweight reading material compared with another Quiz Kid, who took Engels and Marx to bed with him.

  23

  HANDICAP RACE

  January 1952. Just over a year is left before someone makes what Linus Pauling will call ‘the greatest advance in biological science of the last hundred years’. A great deal has to be accomplished in those few months, and some crucial pieces of the puzzle are still missing or do not quite fit. What we can see of DNA is like a portrait of someone familiar, from which some vandal has cut out the features that make the face instantly recognisable.

  Before Christmas, the ‘people at King’s’ rightly poured derision on the inside-out Crick-Watson model of DNA, but they have nothing better to offer. They do not even know how many strands of DNA are in there. One strand is not enough to account for the high density of DNA, and a single-stranded molecule would wobble about all over the place. Maurice Wilkins believes that three chains are more likely than two, even though Bruce Fraser’s three-stranded edifice did not fit the data. For the moment, everyone agrees that the strand of DNA is helical – but this assumption is about to be shaken.

  Rosalind Franklin is convinced that the phosphate groups lie on the outside of DNA, but its internal anatomy is a total mystery. There are a few hints, which are as helpful as random peeps inside an abdomen during keyhole surgery. Astbury has shown that the bases are stacked like a pile of levitating plates, and Masson Gulland has proved that they are held together by hydrogen bonds – but nobody has any idea about how one base is tied to another. And what about Erwin Chargaff’s tantalising match of the base ratios, A = T and C = G? Is this just another of nature’s coincidences? Or is it a vital clue that will somehow make sense of the whole sorry mess?

  Working out a plausible structure of DNA will be a magnificent triumph, but will add little unless it also gives an insight into how DNA works. The Crick-Watson model was not only structurally cack-handed; it stood there with no obvious sense of purpose. If DNA really is the stuff of genes – and, even now, some die-hard protein supremacists are still unconvinced – then it must be able to fulfil the two vital biological functions demanded of it.

  First, from its privileged position inside the nucleus, it must direct all the cell’s activities of daily living, from making structural proteins and the enzymes that control metabolism, to special operations such as muscle contraction, hormone secretion and firing up nerves with electricity. André Boivin believed that DNA is the ‘primary controlling centre�
��, commanding RNA in the cytoplasm (the ‘secondary controlling centre’) to make proteins, which then do everything else. His scheme fits the evidence – but how does DNA control RNA? The structure of DNA must at least give us a hint.

  Second, and just as perplexing, DNA must be able to duplicate its own structure, so that each chromosome can create a perfect replica of itself, and one copy can be given to each daughter cell during cell division. Self-replication is an astonishing process: unimaginably fast (just an hour to copy every last bit of information in the 46 chromosomes of humans), 100 per cent complete and 100 per cent accurate.

  Those are the scientific challenges. Further layers of complexity and intrigue are added by the people involved, their personalities and what drives them. The process has already drifted away from a dignified march of discovery, and is at risk of degenerating into a scramble for a prize that, a year earlier, would not have been seen as worth fighting over. Logically, this should be a one-horse race, because Bill Astbury has dropped out in favour of bacterial flagella, and Watson and Crick have been disqualified for ungentlemanly behaviour. However, the only remaining runner – King’s – is a double act, with two notably independent riders who do not know whether they are heading in the right direction. And Wilkins and Franklin cannot assume that they will have the field to themselves for much longer. Crick and Watson are obsessed by DNA, ambitious and devious. Can they be trusted to stay out of the race? And there may also be a late entrant: the dark horse called Linus Pauling, who wanted to get his hands on Wilkins’s photographs of DNA. Pauling has gone quiet, but that silence could be as deceptive as the one that preceded his triumphant unveiling of the alpha-helix.

  All in all, the closing months of the story promise an exciting spectacle and a breakneck gallop to the finishing line. And even though you know the ending, you should be prepared for some surprises along the way.

  Fair play

  Maurice Wilkins started the New Year of 1952 at low ebb. The ‘fiasco’ in Cambridge before Christmas had left him dispirited – and totally unprepared for a phone call from John Kendrew, asking if he wished to jump ship and come to work in the Cavendish with Crick and Watson. Wilkins asked what was on offer and Kendrew told him, ‘They are very bright.’ Dreading a row with Randall and Franklin, Wilkins said no.

  At the end of January, Wilkins received another memo from John Randall, telling him that DNA was holding back his ultraviolet studies of living cells. ‘Some action is required,’ Randall reminded him ominously. Wilkins ignored the warning, even though DNA was causing him much frustration and misery. Chargaff’s DNA was not as good as Signer’s. Its fibres were ‘less graceful’ to handle, and it refused to produce clear X-ray images. Wilkins had come to regret his peace offering – handing over all the remaining Signer DNA to Franklin – especially as she now avoided him completely and had clearly told Ray Gosling to keep him in the dark. And Alec Stokes, bored with sitting in the doldrums of the ‘DNA muddles’, was drifting away to other projects.

  Wilkins did his best to re-establish diplomatic relations with Franklin, but the model fiasco had turned her hard against him; perhaps she thought him too close to the ‘clowns’ who had exploited her data. When Wilkins suggested that they might meet regularly to catch up, just as Bragg and Perutz did in Cambridge, she put him down by retorting that Bragg was a Nobel prizewinner. So they continued on their separate, diverging paths.

  It was only later that spring when Wilkins’s luck finally improved, thanks to a close relative of the cuttlefish. The sperm sacs of squid were even more amenable to X-ray studies, presumably because the spermatozoa lined up in a tighter, near-parallel formation. Using a new camera that he had built, Wilkins obtained from them the beautifully emphatic ‘X’ patterns which indicated that DNA had a helical structure.

  By now, relations with Crick and Watson had thawed somewhat. Wilkins maintained ‘friendly social contact’ with both, especially Crick, but pointedly ‘did not discuss DNA’.

  In mid-May, Wilkins escaped from King’s for another European adventure that combined work and pleasure. The focal point was Bern, to get more of Rudolf Signer’s magical DNA fibres. Wilkins had written to ask Signer if he could visit his lab, received an effusive reply, and set off with high hopes. En route, he enjoyed a few days of quality time with his German girlfriend, which turned into an emotional roller-coaster. This may explain why his guard was down when he wrote a four-page letter to Crick while on the train from Innsbruck to Zürich. He and his ‘young friend’ had enjoyed a whirlwind tour of artists and beer cellars in Munich, then walked under the orange trees in Bolzano, and spent a ‘wonderful day’ skiing in Selva.

  Next stop: ‘Signer, the DNA man’. And speaking of DNA: ‘I have got much better X-ray pictures of squid sperm, with a whole series of helical layer lines.’ Wilkins sketched the image – an array of short horizontal dashes that spelled out the now classic X (see Figure 24.1). ‘I am really getting down to the job,’ he continued. ‘I think the picture holds a key not yet recognised which will then more or less guide us directly to the model . . . If helices are right, we will hit on the explanation soon.’

  Luckily, his bête noire at King’s had been neutralised. ‘Franklin barks often but doesn’t succeed in biting . . . I was in a bad way about it all when I last saw you . . . but since I reorganised my time so that I can concentrate on the job, she no longer gets under my skin.’ And now, hopefully, he and Crick could get back to normal. The ‘business between you people and us over DNA’ was in the past, and Wilkins looked forward to ‘discussing all our latest ideas and results with you again’. He added, ‘Why don’t you come and have lunch with me when you’re next in town?’ and ended cheerily, ‘I hope Bragg neither barks nor bites and your unit is filled with happiness. If these hopes seem foolishly extravagant, please forgive me.’

  Unfortunately, Bern turned out to be a waste of time. Rudolf Signer was delighted to see Wilkins again but had no DNA; he had given it all away at the London meeting two years earlier and had not planned to make any more. Wilkins returned downcast to London and the frustrations of Chargaff’s DNA, but not for long. He had been invited to Rio de Janeiro for a two-month sabbatical to continue his ingenious microscopic studies of living cells. While there, he slipped in some DNA research, collecting insect sperm and eyeing up museum specimens of the giant squid’s sperm sacs, pickled in ship’s brandy. His own description makes this South American odyssey sound more like a holiday than a sabbatical: dancing in the favelas of Rio, flying over the smoking crater of a live volcano in Peru, hiking up to Machu Picchu.

  London was very dull by comparison when he returned in late September 1952, with two obligations hanging over him. First, he wrote a short paper on DNA in cuttlefish and squid sperm. He added Randall’s name as second author, even though – just as with those disputed papers back in Birmingham – his chief had not contributed anything. Their paper was just over a page long and promised that ‘a full account of this work will be published later’. The results were nothing like the clear X that he had drawn on his letter to Crick; instead, there was a photograph showing vague concentric arcs, and the word ‘helix’ was never mentioned. Wilkins was happy to placate Randall, but was keeping the ace in his hand well hidden.

  Wilkins’s second obligation was to purge himself of the memories of his German girlfriend. Despite the orange trees of Bolzano and the pistes at Selva, they had decided to go their separate ways. Back in his flat, he smashed up everything that she had given him.

  Exclusion zone

  Meanwhile, Rosalind Franklin had been struggling with relationships of her own. She led a double life that oscillated between gaiety and misery. Outside King’s, she was happy, social and enmeshed in a network of family and friends, including evenings out with the leader of a symphony orchestra. At work, she was isolated, moody and withdrawn. She came across as aloof, behaving and speaking like an aristocrat; out of earshot, she was ‘Rosie’, just as Wilkins was ‘Uncle Maurice’ and Ra
ndall ‘JT’. Her only confidantes were the ever-loyal PhD student Ray Gosling, a motherly photographic technician and Bruce Fraser’s wife Mary, who learned that Franklin smuggled special X-ray film from France into England, tucked in her bra. Everyone else caught only rare glimpses of her alter ego. When Franklin discovered that she and Margaret Pratt, one of the PhD students, were both heading for Shropshire one weekend, she suggested that they meet up for a walk. They climbed Caer Caradoc together; Pratt was surprised by the warmth and friendliness of the woman who usually kept everyone at arm’s length. And one evening a technician was astonished by Franklin’s Cinderellalike transformation, when she swept in to check an experiment, almost unrecognisable in an evening dress.

  If her colleagues wondered what she thought of them, they would have found the answer in a letter she wrote to her American friend Anne Sayre in early March 1952. The ‘very young ones’ were ‘thoroughly nice . . . but none of them brilliant’. A couple of the older ones were ‘good and pleasant’. The other middle and senior people were ‘positively repulsive’, without ‘a single first-class or even good brain’.

  As far as Wilkins was concerned, Franklin’s lab was a no-go area with a news blackout. There were few clues about what went on in there: no papers or presentations, just brief progress reports for her fellowship and the annual visit in December of the MRC Biophysics Committee. In reality, a variable feast lay behind her door. She and Gosling had raced ahead in one direction, only to get bogged down when trying to explore terrain that initially appeared non-treacherous. But they struck some real gold: enough for them to write the first paper ever to claim that DNA was a helix, and – even though Franklin never knew this – some vital clues that enabled Jim Watson and Francis Crick to win their places in history.

 

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