Unravelling the Double Helix

by Gareth Williams

  The Double Helix is written like a bestseller, not a historical record. As ‘a personal account of the discovery of the structure of DNA’, it is unashamedly Watson-centric: seen through his twenty-three-year-old eyes and recalled fifteen years later with no attempt to iron out his ‘youthful arrogance’. Unleashed in post-war England, the brash and immature Watson is obsessively focused (in between tennis and popsies) on DNA as a means to an end. As he explains to a friend, ‘I was racing Peter’s father [Pauling] for the Nobel Prize.’

  The book opens memorably – ‘I have never seen Francis Crick in a modest mood’ – and ends whimsically in Paris, even before their big paper comes out in Nature, with Watson deciding on his twenty-fifth birthday that he is now ‘too old to be unusual’. The story of DNA is big, but needs help to keep the pages turning. Watson could not do much about the lack of sex and violence, but he enlivens the plot by inventing a villain and a dash of treachery. There are two moments of high drama: Watson’s eureka morning which ends with Crick telling everyone in the Eagle that they have found the secret of life; and Watson’s visit to King’s where he is all but assaulted by a furious Rosalind Franklin, and then is shown her revelatory Photograph 51 by Wilkins.

  Watson admits that ‘other participants might tell parts of the story in other ways’, and they did. Crick was surprised by the repeated references to racing for a Nobel Prize: ‘Perutz, Kendrew and I never heard Jim talk in this way, so if he really was thinking about Stockholm, he kept it to himself.’ Poetic licence also imbues Watson’s descriptions of the dramatic climaxes; Crick had no memory of the Eagle episode,§ while Wilkins dismissed Watson’s account of Franklin’s ‘assault’ as ‘exaggerated and ridiculous’.

  Predictably, Watson’s characterisations of the ‘other participants’ provoked the strongest reactions. Wilkins was dismayed to find himself portrayed as (in his words) ‘bumbling and taciturn’ and unable to grasp that he was ‘holding dynamite like DNA’. Francis Crick – Watson’s intellectual equal and soulmate – must have felt the most acute pain of betrayal, for example on reading that: ‘Already for thirty-five years he had not stopped talking and almost nothing of fundamental value had emerged.’

  The victim of Watson’s cruellest caricature was denied the right of reply; Rosalind Franklin had been dead for ten years when The Double Helix was published. ‘Rosy’, as Watson calls her, is introduced early as Wilkins’s ‘assistant’ who claims that ‘she had been given DNA for her own problem’. Watson thinks that she is ‘not unattractive and might have been quite stunning had she taken even a mild interest in clothes’ – but her dresses ‘showed all the imagination of English blue-stocking adolescents’. Rosy has ‘a good brain’ but has fallen out with Wilkins and is ‘the real problem’ obstructing DNA research at King’s. ‘Clearly Rosy had to go or be put in her place. The former was obviously preferable because [of] her belligerent moods . . . The thought could not be avoided that the best home for a feminist was in another person’s lab.’

  Thereafter, Watson steadily develops Franklin’s role as the villain of the piece, with ‘a sharp, stubborn mind, caught in her self-made antihelical trap’. The page that he devotes to her in the Epilogue feels awkward and contrived. He praises her ‘superb’ X-ray studies on DNA, her work on TMV, and her ‘exemplary courage and integrity’ in continuing to work while mortally ill. ‘Years too late’, Watson realised ‘the struggles that the intelligent woman faces to be accepted by scientific world which often regard women as mere diversions from serious thinking’. In the Epilogue, he admits that his ‘initial impressions of her, both scientific and personal (as recorded in the early pages of this book) were often wrong’. However, he let that flawed portrayal stand; after all, to have corrected it would only have spoiled a good story.

  The Double Helix was a blockbuster that caused much collateral damage. It smashed the bonds which had created one of the most famous double acts in the history of science. Crick eventually forgave Watson, but they never re-established their effortless symbiosis. Max Perutz was also estranged; Watson had to apologise publicly in Science for implying that Perutz had handed over confidential crystallographic data from Franklin.

  Not surprisingly, Watson’s ‘brutal’ parody of Rosalind Franklin stirred up a fierce backlash. Aaron Klug wrote detailed and forceful articles about her ‘crucial contributions’; a line by line analysis of her lab notebooks convinced him that she had been just ‘two half-steps’ away from discovering the double helix in February 1953. Three books also set out to right the wrongs perpetrated by Watson. One, by Franklin’s sister, is balanced and evidence-based. The other two, in attempting to ‘make the protest that Rosalind could no longer make herself’, resurrect her as a tragic heroine, the victim of male chauvinistic piggery and a feminist icon – an identity which was also unfamiliar to those who had known her.

  The main victim of pro-Franklin retribution was not Watson, but Maurice Wilkins, who was painted as the immediate cause of Franklin’s oppression and misery. Being cast as the ‘most prominent demon’ prompted Wilkins to write his autobiography, as ‘my attempt to respond to those questions and to tell my side of the story’. Wilkins was easily bruised – he had, after all, sought psychotherapy to help cope with a dispute over authorship of a paper – and the impact on him is painfully apparent from the matter-of-fact account in his autobiography.

  The last time Franklin saw Watson, they were friends; so why did he pick on her? Her prickly character and refusal to share her results with Wilkins made her an obvious target. And of course she was unable to sue, or even demand an apology.

  The Double Helix brought immortality to its main characters. Paradoxically, the main beneficiary was Rosalind Franklin, who is now forever tied into the double helix as tightly as Watson, Crick and Wilkins. Franklin herself might have been amused by this. For her, DNA had been like the forms of carbon in coal: a phase in her career from which she had moved on.

  Jim Watson also carved himself a place in history with his book. He might have been the brilliant leader of the pack in spring 1953, but a dozen years later he could have been mistaken for an also-ran. Crick and Wilkins were still at the top of their game, while Watson squeezed out just one minor scientific paper after sharing the Nobel Prize in 1962. He had moved away from the lab; as Erwin Chargaff said (probably with vitriolic intent), he had become ‘an able, effective administrator of science’.

  Perhaps The Double Helix was Watson’s farewell to hands-on research. If it was also his bid to ensure that he would not be forgotten, it was remarkably successful.

  * Nobel Prize for Chemistry (1982), President of the Royal Society (1995–2000)

  † Nobel Prizes are never awarded posthumously.

  ‡ Watson’s addition of the Epilogue was not entirely spontaneous. The publisher insisted on it, to reduce the risk of a backlash from Franklin’s family.

  § In 2005, Watson admitted that he had invented Crick’s outburst in the Eagle.

  26

  RETROSPECTIVE

  It took the double helix a long time to complete the process described by William Blake: ‘What is now proved was once, only imagin’d.’ In March 1953, imagination became a theoretical construct with a reasonable probability of being correct, but it took another seven years for Maurice Wilkins to refine the structure of DNA. Definitive confirmation only came twenty-five years after that, with a high-resolution X-ray analysis of short stretches of an artificial DNA sequence, made to order in the laboratory.

  The structure of DNA was always destined to be solved. It was not like a statue lying unimagined inside a block of Carrara marble, which could only be created by the hands of Michelangelo. Instead, it was like an incredible fossil, waiting indifferently for the moment when the last fragment of matrix is chipped away to reveal it in all its glory. Francis Crick reckoned that someone would have discovered the double helix within another two or three years, and speculated about who that might have been if ‘Watson had been killed by a tennis ba
ll’. Not himself, he thought, and Bragg concurred: ‘Watson’s enthusiasm was so enormous; I don’t think Crick would ever have done it.’ Crick believed that Rosalind Franklin was only ‘two steps’ away from the solution in early 1953, but then ruled herself out by turning from DNA to viruses. Aaron Klug thought that she came even closer; one of his annotations on a photocopy of her lab notes reads simply, ‘Nearly there’. In Crick’s assessment, Maurice Wilkins lagged behind Franklin, although Wilkins felt that Crick never appreciated how tantalisingly close he was to working out what the base ratios really meant. And somewhere behind Wilkins came Linus Pauling, who took a surprisingly long time to accept the faults in his own ill-fated model.

  The story of the double helix is a prime example of history being written by the victors. Jim Watson’s public lecture of 2005 can be found online under two subtly different titles: ‘How we discovered the structure of DNA’ and ‘How I discovered the structure of DNA’. In fact, this discovery was not a solo performance, or even a two-man show. It was the culmination of an epic saga that sprawled across eight decades and two continents, and pulled in hundreds of people. Wilkins envisaged the contributors as a human pyramid, with those at the top standing on the shoulders of those who had gone before.

  Of all the cast, only two broke entirely new ground – Friedrich Miescher, when he discovered nuclein, and Fred Griffith, in showing that genetic material could be passed artificially from one living organism to another. Everyone else had something already established to work on. Those two true pioneers, like most of the rest of the cast, are now long forgotten. I had never heard of Miescher, Levene, Kossel, Griffith or Avery. Had you?

  Who deserves the greatest share of the glory? Watson and Crick saw no need even to ask the question. Max Perutz believed that the enigma of DNA ‘could only be solved by a tremendous leap of the imagination’, and it was Watson who made that leap. According to Crick, Watson’s realisation of how the base pairs fitted together was serendipitous, but nobody else had the ‘prepared mind’ to see the significance of the chance finding. And they alone were truly on the scent: ‘In blundering around we struck gold, but the fact remains that we were looking for gold . . . asking the right questions.’

  Another fact remains, which Watson and Crick always seemed reluctant to acknowledge. Other people had already prospected for, located and dug out the gold, and handed it to them on a plate with a minimum of dross. Aaron Klug offered his own interpretation of the process: ‘The structure was solved by Francis Crick and James Watson, using X-ray diffraction data from fibres of DNA obtained by Rosalind Franklin.’ Crick and Watson looked down on the pedestrian work of ‘the people at King’s’, but they were the only authors on the trilogy of Nature papers who never laid a finger on DNA in the lab. The Cambridge duo gorged themselves on data from King’s, but gave little or nothing back. In purely biological terms, that relationship was not even symbiotic, but parasitic.

  Science can be a messy business; ‘niceness’ is not listed among desirable qualities, let alone essential ones, for a successful researcher. Science will only move forward if scientists look in that direction, and it has been argued that ‘A science which hesitates to forget its founders is lost’. Ideally, though, the founders should not be kicked in the teeth during the scramble to climb on their shoulders in order to see further.

  The story of DNA is a display case for scientists behaving badly; as well as sharp eyes and sharp minds, some had viciously sharp elbows. The fine art of obstructionism is nicely shown at several points. Examples include the ‘absurd wet blanket’ of the tetranucleotide hypothesis with which Phoebus Levene tried unsuccessfully to smother his own baby, DNA; and Alfred Mirsky, hell-bent on demolishing Avery’s work, no matter what the evidence was telling everybody else. Readers may also have spotted candidates for one of the academic stereotypes identified by EM. Cornford in the Cambridge of the early 1900s. The Young Man in a Hurry is ‘a narrow-minded and ridiculously youthful prig . . . inexperienced enough to imagine that something might be done before very long, and even to suggest definite things . . . and afflicted with a conscience, which is apt to break out, like measles, in patches’.

  Supporting cast

  Oswald Avery made a clean break with the Rockefeller and all that it stood for when he moved to join his brother Roy in 1948. The quiet life in Nashville appeared to suit him. He made no effort to write the book that he had thought about many times: a biography of the pneumococcus, provisionally entitled The Sugar-Coated Microbe.

  A reminder of his previous life came in 1950, with a letter from Stockholm announcing that he had won a major prize. It was not the Big One, however, but the Pasteur Medal of the Royal Swedish Microbiological Society. In all, Avery was nominated forty-four times for a Nobel Prize, thirty of them for his work on the pneumococcus, but he never made the cut. The ‘failure of the men in Stockholm’ to recognise Avery’s achievements caused widespread bemusement in the scientific community. His demonstration that the genetic material is DNA was rated by Joshua Lederberg (Nobel Prize in Physiology or Medicine, 1958) as ‘the seminal discovery’ in twentieth-century biology; others argued that Avery had done enough for two Nobel Prizes.

  The Nobel Prize Committee had its reasons. At first, they viewed his DNA work as ‘potentially important’ but in need of further evidence. Subsequent confirmation that DNA was the stuff of genes in other bacteria and in viruses was not enough, while the elucidation of double helix and the DNA copying mechanism was too tangential. Anyway, Avery was too old.*

  Everyone makes mistakes, and the Committee members were only human. They were not some scientific pantheon, just the twenty-five professors of the Karolinska Institute (Stockholm’s medical school), briefed by a working party that comprised three of their number. A few were world-class and impartial; others were neither of those things, and some had a conflict of interest because they regarded themselves as Prize material. Those who argued consistently against Avery’s nomination included Torbjörn Caspersson, a protein supremacist who believed that DNA was just a scaffold for the genetic protein. And it is likely that the poisonous negativity of Avery’s nemesis, Alfred Mirsky, would have permeated through to the decision-makers.

  Avery’s last chance to hear good news from Stockholm came – and went – in October 1954. A few weeks earlier, while enjoying his annual pilgrimage to Deer Isle on the coast of Maine, Avery had been laid low by severe abdominal pains. When inoperable liver cancer was diagnosed, Avery faced his last few months philosophically and with no hint of self-pity or ‘disappointment is my daily bread’. He died peacefully on 20 February 1955, aged seventy-seven.

  The passing of this quiet, unassuming and uncomplaining man unleashed a torrent of affection and admiration. Avery was remembered both for ‘the art with which he composed his character and his life’, and as ‘the most deserving scientist never to be awarded a Nobel Prize’. That last accolade was significant, as it came from one of the Nobel Committee members who declined to fight Avery’s corner.

  The Rockefeller Institute celebrated Avery in its own way and in its own time. ‘DNA’ did not appear in the index of an authoritative history of the Institute published in 1964, and Avery’s work is dismissed in a page (the same coverage as studies of sweat glands). A more substantial monument, ‘erected by grateful colleagues and friends’, was the Avery Memorial Gateway which guards the north-western entrance to the Rockefeller University campus. It is an imposing structure of red Canadian granite, with plenty of room to summarise Avery’s achievements. There is, however, only a brief inscription:

  In memory of Oswald T Avery, 1877–1955

  A member of the Faculty of the Rockefeller Institute,

  1913–1948

  In 2004, Avery was belatedly admitted to the Canadian Scientific Hall of Fame; but in a compendium of American Scientists published ten years after that, there is no entry between Apgar, V. and Axel, R.

  Two of Avery’s bright young things returned to honour their old chief
at the inauguration of the Gateway on 29 September 1965 – his co-authors on the big 1944 paper (Figure 26.1). Both were doing well. Colin MacLeod was Professor of Medicine at New York University, an international expert on cholera, and had served as a senior scientific adviser to presidents John F. Kennedy and Lyndon B. Johnson. The fight against cholera later took him to London in February 1972, en route to a conference in Dacca, just a few weeks before he was due to give the Fourth Fred Griffith Memorial Lecture to the Society for General Microbiology. MacLeod stayed overnight at the London Airport Hotel but failed to board the plane for Dacca the next morning. He had died in his sleep, aged sixty-three.

  Maclyn McCarty was now Physician-in-Chief of the Rockefeller University Hospital (on his way to becoming Vice-President), and editor of the Journal of Experimental Medicine. A decade after the Gateway ceremony, he and MacLeod could easily have fallen out over a passage in Robert Olby’s recently published The Path to the Double Helix. MacLeod was quoted as saying that ‘by the time McCarty joined us, we were virtually certain of what we were dealing with . . . He was a great help in tying things down.’ McCarty later confessed that he was ‘upset’ to read this trivialisation of his contribution but, in the spirit of forgiveness, wrote it off as a trick of MacLeod’s memory. He was unable to check directly; by then, MacLeod had been dead for three years.

  Figure 26.1 Colin MacLeod (left) and Maclyn McCarty at the inauguration of the Avery Memorial Gateway, Rockefeller University, September 1965.

  In 1985, McCarty wrote The Transforming Principle, a self-effacing, good-natured account of his time with Avery. He dedicated his book to:

  The memory of my two colleagues in the search: Oswald Theodore Avery, who was not inclined to write such a book, and Colin Munro MacLeod, who ran out of time before he could do it.