At lunchtime on February 28 1953 Francis Crick rushed into The Eagle, a pub in Cambridge, England, and told everybody there that he and James Watson had found the secret of life.
They had worked out the structure of DNA, the substance passed from parents to offspring that determines the appearance and physiology of every living organism.
DNA carries hereditary information in the form of a code, which consists of strings of molecules called “bases”. Genes are composed of DNA, made up of sugar phosphates and sequences of these four large nitrogenous molecules — adenine, thymine, guanine and cytosine. Less than 50 years later, in 2001 the sequence of bases in humans, or the human genome, was published. This year marks the 50th anniversary of the formal scientific publication of the structure of DNA on April 25 1953.
Crick and Watson won a Nobel Prize for the discovery but were it not for their scientific shenanigans Rosalind Franklin, a pioneering colleague, might well be commemorated today as the discoverer of DNA.
Franklin (1920 to 1958) earned a PhD in physical chemistry at Cambridge University in 1945. But female students did not count as full members of the university worthy of degrees, so she did not graduate. Watson and Crick treated Franklin with the typical male chauvinism of the time. Crick later said they did not take her seriously, patronised her and at first assumed her deductions about DNA were unsound.
Watson and Crick’s approach to the problem was to build a scale model of part of a molecule of DNA by trying to fit the component molecules together. Model building was an accepted method of working out the structure of large molecules. However, as crystallographer JD Bernal pointed out, it is easy to construct a model, but only with information from X-ray diffraction photographs can researchers construct the correct model.
The researchers knew that DNA contained long strands of alternating sugar and phosphate molecules and four kinds of chemical bases. But the first model Crick and Watson built was entirely wrong. Franklin drew attention to problems with their model on a visit to their laboratory in Cambridge.
She had learned the technique of X-ray diffraction in Paris, where she worked after gaining her degree. A beam of X-rays passed through a crystal is diffracted by the crystal’s atoms and produces a pattern of dots and shadows on photographic paper. These reveal information about the internal structure of the crystal.
In 1951 John Randall employed Franklin at King’s College, London, to investigate DNA. Maurice Wilkins, who had been working on the project without much success, was on holiday when she was appointed. When he returned Wilkins assumed Franklin would produce X-ray pictures that he and a colleague, Alec Stokes, would analyse and interpret. But Franklin defended her right to independence.
For Franklin King’s College was a shock in a number of ways. Women were not allowed in the senior common room where some staff ate lunch, in contrast to the mealtime camaraderie she had enjoyed in Paris, where women were accepted unreservedly.
Franklin’s photographs of DNA showed that the molecule is helical. In her notebook she drew a diagram of a double helix joined at one end. Through laborious calculations based on her photographs she obtained measurements of the molecule: lengths, widths, angles and proof of the exact type of crystal structure. On December 5 1952 she gave a written report of her unpublished results to Randall. He passed it on to the Medical Research Council Committee with her application for funding to continue her research. From that time events moved at breakneck speed.
Franklin disliked the stuffy King’s College and arranged to join the renowned crystallographer JD Bernal’s group at Birkbeck College. Wilkins was to supervise her PhD student, Raymond Gosling, who showed him one of Franklin’s prime photographs and other results she had obtained. Wilkins then showed Watson the photograph and gave him Franklin’s calculation of the length of one turn of the helix. Watson made a sketch of the photograph. Franklin was never told that her rival had seen her work.
Linus Pauling, a scientist in the United States, then published an erroneous DNA structure containing three backbones. Bragg decided on January 31 1953 that Crick and Watson should resume their model building before Pauling perceived his error. Crick and Watson had already started building three backbone models, but once they knew about Franklin’s photograph they worked with two backbones and, as she had suggested, tried to fit the bases in the centre of the structure.
Worse was to follow. Max Perutz, one of Crick and Watson’s colleagues, was a member of the Medical Research Council Committee. In the second week of February he gave them Franklin’s report on her unpublished research results in which she specified the measurements of the crystal structure precisely.
South African molecular biologist and Nobel laureate Aaron Klug, who later worked with Franklin, says that to her dying day she did not know that her results had been pirated.
Klug says Franklin should have co-authored the announcement of the discovery with Watson and Crick.
The model of the chains was accurately constructed on the basis of Franklin’s measurements. In mid-February Watson tried, without success, to fit the four kinds of bases into the model. A colleague, Jerry Donohue, told Watson to try a different form of the bases.
Each occurs in two shapes, called enol and keto forms. On February 28 1953 Watson cut cardboard shapes of the bases using the keto forms instead of the enol. He moved the shapes around on his desk and suddenly found that they slotted together in unlike pairs, with each pair having exactly the same width. They would fit inside the two parallel chains exactly.
At lunchtime that day Crick made his announcement in The Eagle. Three letters to Nature appeared on April 25: the first from Crick and Watson; the second from Wilkins and others on preliminary work at King’s College; and the third, with the prime photograph captioned “strongly characteristic of a helical structure”, from Franklin and Gosling.
Franklin and Gosling’s paper concluded: “Thus our general ideas are consistent with the model proposed by Crick and Watson.”
“So indeed they should have been, considering that the Watson-Crick model was in large part derived from her work,” wrote Franklin’s biographer, Brenda Maddox.
On the basis of notebooks and a manuscript dated March 17 1953, Klug and Crick consider that Franklin was close to finding the structure when the model was completed. She might well have got there first. She was not eligible to share Watson, Crick and Wilkins’s Nobel Prize in 1962 because she had died of cancer in 1958 and the prizes are not awarded posthumously.
Over the decades Crick, Watson and Wilkins have been credited with Franklin’s X-ray analyses, but the injustice of this is now well-known. Memorials have been dedicated to Franklin, including a fund for gifted young women scientists. In 1995, Newnham, her college at Cambridge, dedicated a residence to her and placed a bust of her in its garden. In 1998 the National Portrait Gallery hung her photograph beside that of Wilkins.
Crick and Watson both delivered speeches when King’s College opened its Franklin-Wilkins Building in March 2000. They acknowledged that Franklin’s contribution was critical to their discovery.
Franklin suffered a grave injustice and it would reflect well on the scientific community if the tide turned in this anniversary year and her name appeared alongside Watson and Crick’s as a discoverer of DNA.