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Fifty years of the DNA Double Helix

"We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest."
- Watson and Crick, Nature, 25 April 1953

In science as in history, some events grow more important with time, as we realise the range and depth of consequences flowing from them. The discovery fifty years ago of the structure of DNA, the material in which our genes are encoded, was the supreme discovery of the new science of molecular biology, and from it have come revolutions in biology and medicine whose enormous potential benefits, and dangers, are only now beginning to be glimpsed.

The structure of DNA - the famous 'double helix' - has unlocked the secrets of inheritance. It enables us to identify and screen for genes that give rise to inherited or other diseases, from haemophilia to breast cancer, and to determine scientifically the paternity of a child or the guilt of a criminal. It has recently allowed us to map the genomes - the complete genetic make-up - of humans, mice, yeast, bacteria, so that we can unravel exactly how one species relates to another. It is helping us to explore what it means to be humans, from the mix of inheritance and environment that shapes our abilities and behaviour to the biology of ageing. It has given birth to the industry of biotechnology, with all its promise and problems in fields from DNA therapy to the genetic modification of plants and animals, including perhaps ourselves.

The double helix was discovered by the molecular biologists James Watson and Francis Crick in Cambridge, England, in a rush of scientific creativity in February 1953. Crick was a 36-year-old Englishman working at Cambridge University's Cavendish Laboratory. James Watson was a 24-year-old American who joined Crick in 1951. They had tried and failed to solve the structure of DNA 18 months earlier. Now the great American chemist Linus Pauling claimed to have made the breakthrough. Watson saw Pauling's yet-to-be-published paper on January 28, 1953, and immediately realised it was in error and that he and Crick could still make the discovery.

Two days later, at King's College in London, an extraordinarily clear x-ray diffraction photograph of the DNA crystal taken by Rosalind Franklin was shown to Watson without her knowledge or permission. "The instant I saw the picture," Watson wrote in his famous book The Double Helix (1968), "my mouth fell open and my pulse began to race." The pattern on Franklin's x-ray was a vital clue, convincing him that the DNA molecule must consist of two chains arranged in a paired helix.

Watson and Crick started building a model on February 4. But how were the two chains held together? How did the four 'bases' of DNA - known by the letters A, T , C, and G - join up with each other? Another crucial clue came on February 19 when Jerry Donohue, who shared Watson and Crick's room at the Cavendish, suggested they use a different chemical form of the four bases - 'keto' instead of 'enol'.

It worked. Watson and Crick quickly realised that the bases always join up in the same pairs, A with T, C with G. This was the secret of inheritance, for any sequence of bases along one chain of the helix - such as A, A, T, C, G - would always be accompanied on the opposite chain by its mirror sequence of T, T, A, G, C. When the two chains of the double helix split apart, each could be used to replicate the sequence. A gene was a particular sequence of the letters, thousands of bases long - a set of chemical instructions that might give rise to blue eyes, or musical ability, or a weak heart.

It was February 28, 1953. According to Watson's account, "Francis winged into The Eagle and told everybody we had discovered the secret of life." A week later, on March 7, they finished their model, a spidery construction of metal rods and plates clamped into position some 6 feet tall. To the biochemists and crystallographers who came to view it, its chemical elegance was powerful evidence of its accuracy.

The model and its proud creators were photographed on 21 May by a young Cambridge photographer, Anthony Barrington Brown, who remembers: "I was affably greeted by a couple of chaps lounging at a desk by the window, drinking coffee. 'What's all this about?' I asked. With an airy wave of the hand one of them, Crick I think, said 'we've got this model' indicating an array of retort stands holding thin brass rods and balls... So I set up my lights and camera and said 'you'd better stand by it and look portentous', which they lamentably failed to do, treating my efforts as a bit of a joke." His unique and classic portrait shows the pair grinning, with the model twisting up between them and a diagram of the two-chained double helix pinned to the wall.

The discovery of the double helix was published in Nature on April 25, 1953 - 'A Structure for Deoxyribonucleic Acid' by Watson, J.F., and Crick, F.H.C. Its famously understated second from last sentence read: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."

The same issue of Nature carried companion papers about DNA from the group at King's College, one by Rosalind Franklin (with her PhD student, Raymond Gosling) and one by Maurice Wilkins and colleagues. Wilkins had done important earlier crystallographic work on DNA, but had fallen out with Franklin after she joined King's in 1951. On May 30, Nature published Watson and Crick's follow-up paper, 'Genetical Implications of the Structure of Deoxyribonucleic Acid'.

The discovery was by no means hailed immediately. It took time for others to be convinced. Pauling clung for a time to his erroneous model. Even Watson and Crick were not at first completely sure their version was right. Discovery and its confirmation are often more complex and protracted than later myth-building allows. But by the second half of the 1950s their structure was vindicated, and its implications began to set the agenda in biology laboratories around the world.

In 1962, Watson and Crick, along with Maurice Wilkins, won the Nobel prize for physiology or medicine for their work on DNA. Rosalind Franklin had died of cancer in 1958, and the Nobel is never awarded posthumously. Whether she might have shared the prize, had she lived, has been much discussed. A maximum of three can share a prize under Nobel rules, so it would have had to be either her or Wilkins along with Watson and Crick, or Watson and Crick on their own.

Fifty years after their momentous discovery, Watson and Crick are still active in science. Watson, who returned to the USA in 1953, became a professor at Harvard in 1961, director of the Cold Spring Harbor Laboratory in 1968, and was head of the Human Genome Project in America in 1989-1992. Crick has since 1977 been at the Salk Institute in La Jolla, California, studying the brain and consciousness.

"Rather than believe that Watson and Crick made the DNA structure, I would rather stress that the structure made Watson and Crick. After all, I was almost totally unknown at the time and Watson was regarded, in most circles, as too bright to be really sound. But what I think is overlooked in such arguments is the intrinsic beauty of the DNA double helix. It is the molecule which has style, quite as much as the scientists."
- Francis Crick, 'The Double Helix: A Personal View', Nature, 26 April 1974.


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