How extremely stupid not to have thought of it!" Thomas Huxley's purported reaction on first hearing of Darwin's idea of natural selection can be repeated in spades for the event whose 50th anniversary is being celebrated this April: the double helix of DNA, surely the greatest biological prize of the 20th century, as natural selection was of the 19th.
James Watson and Francis Crick got the credit, the Nobel Prize and a place in the scientific pantheon. But their success generated-and still generates-occasional resentment, not least because of Watson's brutally honest recounting, in The Double Helix, of how they stumbled to success, treading on the toes of others as they went. Some of those others spent the rest of their lives kicking themselves.
In the case of DNA, unlike most scientific breakthroughs, there was a true Eureka moment. It came on 28th February 1953, at about 9.30am in a large, cold room in the Cavendish Laboratory. A tall, skinny man sits alone at a table, playing with cardboard cutouts he made the night before. Suddenly he sees something that has never been seen before, something that can never be unseen again. Two of his cutouts, put together, are the same shape as the two other cutouts put together. This, he begins to realise, is the secret of life. You could string together combinations of the four "bases" in any order on one of the two strands of DNA for an infinite length, and because of the shape-fitting effect, that order would be faithfully reproduced in negative on the other strand. Life's ability to copy itself was explained.
That man was Jim Watson. He was joined by Francis Crick about an hour later. Crick had already done key calculations that told them they were looking for a double helix with chains running in opposite directions and he now saw another reason that the cutout base pairs had to be right: they fitted into the helices at just the angle that he had calculated. But however you replay the tape, Watson is always alone when the penny first drops. It was base-pairing, not the double helix per se, that was the great discovery.
Yet Watson (below) and Crick could never have made the discovery without standing on the shoulders of many others. Without the intervention of Jerry Donohue, an American post-doc, they would have used the wrong models of bases. Without the data produced by Rosalind Franklin and Raymond Gosling in King's College London in 1952, they would never have known the dimensions and angles of the helices. Without the first X-ray photographs done by Maurice Wilkins in 1951, they might never have suspected that DNA was helical. Without the example of Linus Pauling's models of the alpha helix in 1951, they would never have thought of building models. Without the base-ratio data of Erwin Chargaff in 1950, they would not have been so excited by the base pairing. Without the work of Sven Furberg in 1949, they might never have guessed that bases could be at right angles to the sugars. Without the bacterial experiments of Oswald Avery in 1944, they would not have known that genes were made of DNA. Without the work of William Astbury in Leeds in 1943, they might never have known that the bases were stacked liked plates. And so you go back up the list of scientific ancestors.
Each of these people has a reason to kick himself or herself, though some, like Erwin Chargaff, preferred to kick Crick and Watson. Chargaff had a key piece of information-the base ratios-and never saw its significance (Crick did at once). Chargaff dismissed the brash young pair when they met in 1952 and failed to listen to what they said about helices. In an interview before his death last year, Chargaff was still bitter.
One of the most interesting might-have-beens was the Norwegian Sven Furberg. Working with JD Bernal at Birkbeck College, he produced X-rays of DNA crystals that uncovered the fact that the bases lay at right angles to the sugars and he started drawing a model of DNA. It was a single helix with dimensions that were almost right. Had he not stopped in 1949 to return to Norway, who knows what he might have achieved? Furberg died in 1983 without saying much on the subject, but Bernal certainly kicked himself in later years for letting the opportunity slip. Rosalind Franklin relied heavily on Furberg's thesis when she began to speculate about the structure.
At the other extreme, Linus Pauling, the king of chemistry, produced a model of DNA in early 1953 that was clearly wrong. Watson attributes this to Pauling's fame. Pauling was so revered at Caltech that he had no one to tell him when he was being foolish. There is another reason. He had no access to X-ray photographs of DNA crystals because, shockingly, he was refused a passport due to his anti-nuclear views and thus had to cancel a European trip in 1952. He wrote to Wilkins at King's, asking to see the photographs. Wilkins procrastinated.
Wilkins's case is a similar chapter of accidents. He was feuding with Rosalind Franklin, who he felt had been hired by their boss John Randall to pinch his work on DNA X-rays. But Franklin was about to leave King's and had already handed the DNA problem back to Wilkins, so he was about to resume work on DNA in February 1953. When I interviewed Crick this February, he said to me: "A very good question to ask is what would have happened if Jim hadn't come along." Answer: Wilkins would have had a clear run at the problem. Without Watson, Crick would not have raced Wilkins and might have helped him.
As for Franklin, the only alternative histories in which she gets sole credit are those in which she acts differently herself. Handed Wilkins's work in 1951, she was granted a year's monopoly (in Britain) on the DNA problem: Watson and Crick were ordered off the case by their boss, Lawrence Bragg, after their failure at the end of 1951, and they sent their model building kit to Wilkins and Franklin. She did brilliant X-ray work, but she despised speculative model building and failed to talk through the problem with those who could have helped her interpret the exquisite data she was getting: Crick, Wilkins and Dorothy Hodgkin, to name three. In July 1952, she went so far as to "announce the death of the helix" in a mock funeral notice.
Watson made Franklin a feminist hero in The Double Helix, a book in which he insulted everybody, regardless of gender and including himself. Notoriously, he wrote: "Though her features were quite strong, she was not unattractive and might have been quite stunning had she taken even a mild interest in clothes." This echoes a sentence from another book about another lucky Jim of the 1950s, Kingsley Amis's Jim Dixon: "What a pity it was, he thought, that she wasn't better-looking, that she didn't read the articles... that told you which colour lipstick went with which natural colouring." Watson had originally intended to call his book Honest Jim, with conscious reference to Kingsley Amis (rather than Joseph Conrad).
Yet Raymond Gosling, Franklin's student, has no time for the theory that Franklin was hard done by. To him, she was a heroine, not a victim. Crick, who became a close friend in the last years of her life, agrees. She undoubtedly could have cracked the problem all by herself in 1952 and claimed a place as the greatest woman scientist of all time, but she did not. Sexism may have played a part, but so did her own caution and her lack of understanding of mathematical symmetry.
Thus it was left to Watson and Crick to claim the prize. They were lucky to be in the right place at the right time, but through sheer determination they had made their own luck. Their towering fame is at least partly justified, too, by their subsequent achievements.
