Rosalind Franklin - King's College London

King's College London

In January 1951, Franklin started working as a research associate at King's College London in the Medical Research Council's (MRC) Biophysics Unit, directed by John Randall. Although originally she was to have worked on X-ray diffraction of proteins and lipids in solution, Randall redirected her work to DNA fibers before she started working at King's since Franklin was to be the only experienced experimental diffraction researcher at King's in 1951. He made this reassignment, even before she started working at King's, because of the following pioneering work by Maurice Wilkins and Raymond Gosling- a Ph.D. student assigned to help Franklin. Even using crude equipment, these two men had obtained an outstanding diffraction picture of DNA which sparked further interest in this molecule. Wilkins and Gosling had been carrying out X-ray diffraction analysis of DNA in the unit since May 1950, but Randall had not informed them that he had asked Franklin to take over both the DNA diffraction work and guidance of Gosling's thesis. Randall's lack of communication about this reassignment significantly contributed to the well documented friction that developed between Wilkins and Franklin.

Franklin, working with her student Raymond Gosling, started to apply her expertise in X-ray diffraction techniques to the structure of DNA. She used a new fine focus X-ray tube and microcamera ordered by Wilkins, but which she refined, adjusted and focused carefully. Drawing upon her physical chemistry background, Franklin also skillfully manipulated the critical hydration of her specimens. When Wilkins inquired about this improved technique, Franklin replied in terms which offended Wilkins as Franklin had "an air of cool superiority". Franklin's habit of intensely looking people in the eye while being concise, impatient and directly confrontational to the point of abrasiveness unnerved many of her colleagues. In stark contrast, Wilkins was very shy, and slowly calculating in speech while he avoided looking anyone directly in the eye. In spite of the intense atmosphere, Franklin and Gosling discovered that there were two forms of DNA: at high humidity (when wet), the DNA fibre became long and thin; when it was dried it became short and fat. These forms were termed DNA "B" and "A" respectively. Because of the intense personality conflict developing between Franklin and Wilkins, Randall divided the work on DNA. Franklin chose the data rich A form while Wilkins selected the "B" form because his preliminary pictures had hinted it might be helical. He showed tremendous insight in this assessment of preliminary data. The X-ray diffraction pictures taken by Franklin at this time have been called, by J. D. Bernal, "amongst the most beautiful X-ray photographs of any substance ever taken".

By the end of 1951 it was generally accepted at King's that the B form of DNA was a helix, but after she had recorded an asymmetrical image in 1952 May, Franklin became unconvinced that the A form of DNA was helical in structure. In July 1952, as a practical joke on Wilkins (who frequently expressed his view that DNA was helical), Franklin and Gosling produced a death notice regretting the 'death' of helical crystalline DNA (A-DNA). During 1952, Rosalind Franklin and Raymond Gosling worked at applying the Patterson function to the X-ray pictures of DNA they had produced. This was a long and labour-intensive approach but would yield significant insight into the structure of the molecule.

By January 1953, Franklin had reconciled her conflicting data and had started to write a series of three draft manuscripts, two of which included a double helical DNA backbone (see below). Her two A form manuscripts reached Acta Crystallographica in Copenhagen on 6 March 1953, one day before Crick and Watson had completed their model. Franklin must have mailed them while the Cambridge team was building their model, and certainly had written them before she knew of their work. On 8 July 1953 she modified one of these "in proof", Acta articles "in light of recent work" by the King's and Cambridge research teams. The third draft paper on the "B" form of DNA, dated 17 March 1953, was discovered years later amongst her papers, by Franklin's Birkbeck colleague, Aaron Klug. He then published an evaluation of the draft's close correlation with the third of the original trio of 25 April 1953 Nature DNA articles. Klug designed this paper to complement the first article he had written defending Franklin's significant contribution to DNA structure. He had written this first article in response to the incomplete picture of Franklin's work depicted in Watson's 1968 memoir, The Double Helix.

As vividly described in The Double Helix, on 30 January 1953, Watson travelled to King's carrying a preprint of Linus Pauling's incorrect proposal for DNA structure. Since Wilkins was not in his office, Watson went to Franklin's lab with his urgent message that they should all collaborate before Pauling discovered his error. The unimpressed Franklin became angry when Watson suggested she did not know how to interpret her own data. Watson hastily retreated, backing into Wilkins who had been attracted by the commotion. Wilkins commiserated with his harried friend and then changed the course of DNA history with the following disclosure. Without Franklin's permission or knowledge, Wilkins showed Watson Franklin's famous photograph 51. Watson, in turn, showed Wilkins a prepublication manuscript by Pauling and Corey. Franklin and Gosling's photo 51 gave the Cambridge pair critical insights into the DNA structure, whereas Pauling and Corey's paper described a molecule remarkably like their first incorrect model.

In February 1953, Francis Crick and James D. Watson of the Cavendish Laboratory in Cambridge University had started to build a model of the B form of DNA using similar data to that available to both teams at King's. Much of their data were derived directly from research done at King's by Wilkins and Franklin. Franklin's research was completed by February 1953, ahead of her move to Birkbeck, and her data were critical. Model building had been applied successfully in the elucidation of the structure of the alpha helix by Linus Pauling in 1951, but Franklin was opposed to prematurely building theoretical models, until sufficient data were obtained properly to guide the model building. She took the view that building a model was to be undertaken only after enough of the structure was known. Ever cautious she wanted to eliminate misleading possibilities. Photographs of her Birkbeck work table show that she routinely used small molecular models, although certainly not ones on the grand scale successfully used at Cambridge for DNA. In the middle of February 1953, Crick's thesis advisor, Max Perutz gave Crick a copy of a report written for a Medical Research Council biophysics committee visit to King's in December 1952, containing many of Franklin's crystallographic calculations. Since Franklin had decided to transfer to Birkbeck College and Randall had insisted that all DNA work must stay at King's, Wilkins was given copies of Franklin's diffraction photographs by Gosling. By 28 February 1953 Watson and Crick felt they had solved the problem enough for Crick to proclaim (in the local pub) that they had "found the secret of life". However they knew they must complete their model before they could be certain.

Watson and Crick finished building their model on 7 March 1953, one day before they received a letter from Wilkins stating that Franklin was finally leaving and they could put "all hands to the pump". This was also one day after Franklin's two A form papers had reached Acta Crystallographica. Wilkins came to see the model the following week, according to Maddox on 12 March, and allegedly informed Gosling on his return to King's. It is uncertain how long it took for Gosling to inform Franklin at Birkbeck, but her original 17 March B form manuscript does not reflect any knowledge of the Cambridge model. Franklin did modify this draft later before publishing it as the third in the trio of 25 April 1953 Nature articles. On 18 March, in response to receiving a copy of their preliminary manuscript, Wilkins penned the following "I think you're a couple of old rogues, but you may well have something".

Crick and Watson then published their model in Nature on 25 April 1953 in an article describing the double-helical structure of DNA with only a footnote acknowledging "having been stimulated by a general knowledge of" Franklin and Wilkin's 'unpublished' contribution. Actually, although it was the bare minimum, they had just enough specific knowledge of Franklin and Gosling's data upon which to base their model. As a result of a deal struck by the two laboratory directors, articles by Wilkins and Franklin, which included their X-ray diffraction data, were modified and then published second and third in the same issue of Nature, seemingly only in support of the Crick and Watson theoretical paper which proposed a model for the B form of DNA. Franklin left King's College London in March 1953 to move to Birkbeck College in a move that had been planned for some time.

Weeks later, on 10 April, Franklin wrote to Crick for permission to see their model. Franklin retained her scepticism for premature model building even after seeing the Crick–Watson model, and remained unimpressed. She is reported to have commented, "It's very pretty, but how are they going to prove it?" As an experimental scientist Franklin seems to have been interested in producing far greater evidence before publishing-as-proven a proposed model. As such her response to the Crick–Watson model was in keeping with her cautious approach to science. However, as documented above, she did not hesitate to publish preliminary ideas about DNA in Acta, even before they could be definitively proven. Most of the scientific community hesitated several years before accepting the double helix proposal. At first mainly geneticists embraced the model because of its obvious genetic implications. Broader acceptance for the DNA double helix did not start until about 1960, and was not openly acknowledged until 1961 during the 1962 Nobel prize nominations. It took Wilkins and his colleagues about seven years to collect enough data to prove and refine the proposed DNA structure. According to the 1961 Crick–Monod letter cited above, this experimental proof, along with Wilkins having initiated the DNA diffraction work, were the reasons why Crick felt that Wilkins should be included in the DNA Nobel prize.