Paris With World War II ending in 1945, Franklin asked Adrienne Weill for help and to let her know of job openings for "a physical chemist who knows very little physical chemistry, but quite a lot about the holes in coal." At a conference in the autumn of 1946, Weill introduced Franklin to Marcel Mathieu, a director of the
Centre national de la recherche scientifique (CNRS), the network of institutes that comprises the major part of the scientific research laboratories supported by the French government. This led to her appointment with
Jacques Mering at the Laboratoire Central des Services Chimiques de l'État in Paris. Franklin joined the
labo (as referred to by the staff) of Mering on 14 February 1947 as one of the fifteen
chercheurs (researchers). Mering was an X-ray crystallographer who applied
X-ray diffraction to the study of rayon and other amorphous substances, in contrast to the thousands of regular crystals that had been studied by this method for many years. and in the regularly published textbook
Chemistry and Physics of Carbon. Mering continued the study of carbon in various forms, using X-ray diffraction and other methods.
King's College London In 1950, Franklin was granted a three-year
Turner & Newall Fellowship to work at
King's College London. In January 1951, she started working as a research associate in the
Medical Research Council's (MRC) Biophysics Unit, directed by
John Randall. Franklin was originally appointed to work on X-ray diffraction of
proteins and
lipids in solution, but Randall redirected her work to DNA fibres because of new developments in the field, and Franklin was to be the only experienced experimental diffraction researcher at King's at the time. Randall made this reassignment, even before Franklin started working at King's, because of the pioneering work by DNA researcher
Maurice Wilkins, and he reassigned
Raymond Gosling, the graduate student who had been working with Wilkins, to be her assistant. In 1950, Swiss chemist
Rudolf Signer in Berne prepared a highly purified DNA sample from calf
thymus. He freely distributed the DNA sample, later referred to as the Signer DNA, in early May 1950 at the meeting of the
Faraday Society in London, and Wilkins was one of the recipients. Even using crude equipment, Wilkins and Gosling had obtained a good-quality diffraction picture of the DNA sample which sparked further interest in this molecule. However, Randall had not indicated to them that he had asked Franklin to take over both the DNA diffraction work and guidance of Gosling's thesis. It was while Wilkins was away on holiday that Randall, in a letter in December 1950, assured Franklin that "as far as the experimental X-ray effort there would be for the moment only yourself and Gosling." Randall's lack of communication about this reassignment significantly contributed to the well-documented friction that developed between Wilkins and Franklin. 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, a critical innovation Franklin supplied was making a camera chamber that could be controlled for its
humidity using different saturated salt solutions. Franklin's habit of intensely looking people in the eye while being concise, impatient and direct 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. With the ingenious humidity-controlling camera, Franklin was soon able to produce X-ray images of better quality than those of Wilkins. She immediately discovered that the DNA sample could exist in two forms: at a relative humidity higher than 75%, the DNA fibre became long and thin; when it was drier, it became short and fat. She originally referred to the former as "wet" and the latter as "crystalline".Franklin then named "
A" and "B" respectively for the "crystalline" and "wet" forms. (The biological functions of A-DNA were only discovered 60 years later.) 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. By the end of 1951, it became generally accepted at King's that the B-DNA was a
helix, but after Franklin had recorded an asymmetrical image in May 1952, Franklin became unconvinced that the A-DNA was a helix. In July 1952, as a practical joke on Wilkins (who frequently expressed his view that both forms of DNA were helical), Franklin and Gosling produced a funeral notice regretting the 'death' of helical A-DNA, which runs:It is with great regret that we have to announce the death, on Friday 18th July 1952 of DNA helix (crystalline). Death followed a protracted illness which an intensive course of Besselised [referring to
Bessel function that was used to analyse the X-ray diffraction patterns] injections had failed to relieve. A memorial service will be held next Monday or Tuesday. It is hoped that Dr M H F Wilkins will speak in memory of the late helix. [Signed Rosalind Franklin and Raymond Gosling.]Throughout 1952, they 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. Franklin was fully committed to experimental data and was sternly against theoretical or model buildings, as she said, "We are not going to speculate, we are going to wait, we are going to let the spots on this photograph tell us what the [DNA] structure is." By January 1953, Franklin had reconciled her conflicting data, concluding that both DNA forms had two helices, and had started to write a series of three draft manuscripts, two of which included a double-helical DNA backbone (see below). Franklin's two A-DNA manuscripts reached
Acta Crystallographica in
Copenhagen on 6 March 1953, the day before Crick and Watson had completed their model on B-DNA. 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 Franklin 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 was on the B-DNA, dated 17 March 1953, which was discovered years later amongst her papers, by Franklin's Birkbeck colleague,
Aaron Klug. He then published in 1974 an evaluation of the draft's close correlation with the third of the original trio of 25 April 1953
Nature DNA articles. As vividly described by Watson, he travelled to King's on 30 January 1953 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 showed Watson Franklin's DNA X-ray image. Watson, in turn, showed Wilkins a prepublication manuscript by Pauling and
Robert Corey, which contained a DNA structure remarkably like their first incorrect model.
Discovery of DNA structure In November 1951, James Watson and Francis Crick of the
Cavendish Laboratory in
Cambridge University had started to build a
molecular model of the B-DNA using data similar to that available to both teams at King's. Based on Franklin's lecture in November 1951 that DNA was helical with either two or three strands, they constructed a triple-helix model, which was immediately proven to be flawed. but Franklin was opposed to prematurely building theoretical models, until sufficient data were obtained to properly guide the model building. She took the view that building a model was to be undertaken only after enough of the structure was known. Franklin's conviction was only reinforced when Pauling and Corey also came up with an erroneous triple-helix model). Ever cautious, Franklin wanted to eliminate misleading possibilities. Photographs of her Birkbeck work table show that Franklin routinely used small molecular models of DNA, although certainly not ones on the grand scale successfully used at Cambridge. The arrival in Cambridge of Linus Pauling's flawed paper in January 1953 prompted the head of the Cavendish Laboratory,
Lawrence Bragg, to encourage Watson and Crick to resume their own model building. Six weeks of intense efforts followed, as they tried to guess how the nucleotide bases pack into the core of the DNA structure, within the broad parameters set by the experimental data from the team at King's, that the structure should contain one or more helices with a repeat distance of 34 Angstroms, with probably ten elements in each repeat; and that the hydrophilic phosphate groups should be on the outside (though as Watson and Crick struggled to come up with a structure, they at times departed from each of these assumptions during the process). This decisively confirmed the 34 Angstrom repeat distance; and established that the structure had C2 symmetry, immediately confirming to Crick that it must contain an equal number of parallel and anti-parallel strands running in opposite directions. However, they knew they must complete their model before they could be certain. The closeness of fit to the experimental data from King's was an essential corroboration of the structure. This was also one day after Franklin's two A-DNA papers had reached
Acta Crystallographica. Wilkins came to see the model the following week, according to Franklin's biographer
Brenda Maddox, on 12 March, and allegedly informed Gosling on his return to King's. One of the most critical and overlooked moments in DNA research was how and when Franklin realised and conceded that B-DNA was a double-helical molecule. When Klug first examined Franklin's documents after her death, he initially came to an impression that Franklin was not convinced of the double-helical nature until the knowledge of the Cambridge model. Her conclusion on the helical nature was evident, though she failed to understand the complete organisation of the DNA strands, as the possibility of two strands running in opposite directions did not occur to her. After the Watson–Crick model was known, there appeared to be only one (hand-written) modification after the typeset at the end of the text which states that their data was consistent with the model, As Franklin considered the double helix, she also realised that the structure would not depend on the detailed order of the bases, and noted that "an infinite variety of nucleotide sequences would be possible to explain the biological specificity of DNA". Franklin retained her scepticism for premature model building even after seeing the Watson–Crick model, and remained unimpressed. Franklin is reported to have commented, "It's very pretty, but how are they going to prove it?" As an experimental scientist, she seems to have been interested in producing far greater evidence before publishing-as-proven a proposed model. Accordingly, Franklin's response to the Watson–Crick model was in keeping with her cautious approach to science. Crick and Watson 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 Wilkins' 'unpublished' contribution." Although it was the bare minimum, they actually 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-DNA.
Birkbeck College of
tobacco mosaic virus Franklin left King's College London in mid-March 1953 for
Birkbeck College, in a move that had been planned for some time and that she described (in a letter to Adrienne Weill in Paris) as "moving from a palace to the slums ... but pleasanter all the same". Franklin was recruited by physics department chair and crystallographer John Desmond Bernal, who was known for promoting female crystallographers. Her new laboratories were housed in 21
Torrington Square, one of a pair of dilapidated and cramped Georgian houses containing several different departments; Franklin frequently took Bernal to task over the careless attitudes of some of the other laboratory staff, notably on one occasion after workers in the Pharmacy department flooded her first-floor laboratory with water. Despite the parting words of Bernal to stop her interest in nucleic acids, Franklin helped Gosling to finish his thesis, although she was no longer his official supervisor. Together, they published the first evidence of double helix in the A form of DNA in the 25 July issue of
Nature. At the end of 1954, Bernal secured funding for Franklin from the
Agricultural Research Council (ARC), which enabled her to work as a senior scientist supervising her own research group.
John Finch, a physics student from
King's College London, subsequently joined Franklin's group, followed by
Kenneth Holmes, a Cambridge graduate, in July 1955. Despite the ARC funding, Franklin wrote to Bernal that the existing facilities remained highly unsuited for conducting research: ...my desk and lab are on the fourth floor, my X-ray tube in the basement, and I am responsible for the work of four people distributed over the basement, first and second floors on two different staircases. This was in direct contradiction to the ideas of the eminent virologist
Norman Pirie, though Franklin's observation ultimately proved correct. Some strenuous opposition came from Franklin's work on TMV. She had observed that the particles were similar in length and had the same number of protein subunits. After sending a draft of her article to Pirie, she received funding despite his opposing views. At this time, Franklin visited
Woods Hole in Massachusetts,
Washington University in Saint Louis,
University of California at Berkeley, and
California Institute of Technology where she contacted various virologists. These researchers helped build her network and allowed her to learn more about work that informed and complemented hers, allowing her to further understand her model. Franklin returned with virus samples. She also benefitted from the promises of collaboration from
Wendell Stanley and
Barry Commoner, prominent American scientists. Franklin assigned the study of the complete structure of TMV to her PhD student Holmes. They soon discovered (published in 1956) that the covering of TMV was protein molecules arranged in helices. Her colleague Klug worked on spherical viruses with his student Finch, with Franklin coordinating and overseeing the work. As a team, from 1956 they started publishing seminal works on TMV, cucumber virus 4 and
turnip yellow mosaic virus. Franklin also had a
research assistant, James Watt, subsidised by the
National Coal Board and was now the leader of the ARC group at Birkbeck. The Birkbeck team members continued working on RNA viruses affecting several plants, including potato, turnip, tomato and pea. In 1955, the team was joined by an American post-doctoral student
Donald Caspar. He worked on the precise location of RNA molecules in TMV. The following year, Caspar and Franklin published individual but complementary papers in the 10 March issue of
Nature, in which they showed that the RNA in TMV is wound along the inner surface of the hollow virus. Caspar was not an enthusiastic writer, and Franklin had to write the entire manuscript for him. Franklin's research grant from ARC expired at the end of 1957, and she was never given the full salary proposed by Birkbeck. After Bernal requested ARC chairman
Lord Rothschild, Franklin was given a one-year extension ending in March 1958.
Expo 58, the first major international fair after World War II, was to be held in Brussels in 1958. Franklin was invited to make a five-foot high model of TMV, which she started in 1957. Her materials included table tennis balls and plastic bicycle handlebar grips. The Brussels world's fair, with an exhibit of her virus model at the International Science Pavilion, opened on 17 April, the day after she died.
Polio virus In 1956, Franklin visited the
University of California, Berkeley, where colleagues suggested her group research the
polio virus. The following year, she applied for a grant from the United States
Public Health Service of the
National Institutes of Health, which approved £10,000 (equivalent to £ in ) for three years, the largest fund ever received at Birkbeck. In her grant application, Franklin mentioned her new interest in animal virus research. Franklin obtained Bernal's consent in July 1957, though serious concerns were raised after she disclosed her intentions to research live, instead of killed, polio virus at Birkbeck. Eventually, Bernal arranged for the virus to be safely stored at the
London School of Hygiene and Tropical Medicine during the group's research. With her group, Franklin then commenced deciphering the structure of the polio virus while it was in a crystalline state. She attempted to mount the virus crystals in capillary tubes for X-ray studies, but was forced to end her work due to her rapidly failing health. After Franklin's death,
Klug succeeded her as group leader, and he, Finch, and Holmes continued researching the structure of the polio virus. They eventually succeeded in obtaining extremely detailed X-ray images of the virus. In June 1959, Klug and Finch published the group's findings, revealing the polio virus to have icosahedral symmetry, and in the same paper suggested the possibility for all spherical viruses to possess the same symmetry, as it permitted the greatest possible number (60) of identical structural units. The team moved to the
Laboratory of Molecular Biology, Cambridge, in 1962 and the old Torrington Square laboratories were demolished four years later in May 1966. ==Personal life==