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Rosalind FRANKLIN

History of Scientific Women

Main achievements: Identification of the DNA molecular structure. Discovery of the DNA double helix.

Rosalind Elsie Franklin was an English chemist and X-ray crystallographer who made critical contributions to the understanding of the fine molecular structures of DNA (deoxyribonucleic acid), RNA, viruses, coal, and graphite. Her DNA work achieved the most fame because DNA plays an essential role in cell metabolism and genetics, and the discovery of its structure helped her co-workers understand how genetic information is passed from parents to their offspring. Franklin is best known for her work on the X-ray diffraction images of DNA which led to the discovery of the DNA double helix.

According to Francis Crick, her data were key in determining the structure and formulating Crick and Watson's 1953 model regarding the structure of DNA. Franklin's images of X-ray diffraction confirming the helical structure of DNA were shown to Watson without her approval or knowledge. This image provided valuable insight into the DNA structure, but Franklin's scientific contributions to the discovery of the double helix are often overlooked. Unpublished drafts of her papers (written just as she was arranging to leave King's College London) show that she had independently determined the overall B-form of the DNA helix and the location of the phosphate groups on the outside of the structure. Moreover, it was a report of Franklin's that convinced Crick and Watson that the backbones had to be on the outside, which was crucial since before this both they and Linus Pauling had independently generated non-illuminating models with the chains inside and the bases pointing outwards. However, her work was published third, in the series of three DNA Nature articles, led by the paper of Watson and Crick which only hinted at her contribution to their hypothesis. Watson has suggested that ideally Franklin would have been awarded the Nobel Prize in Chemistry, along with Maurice Wilkins. After finishing her portion of the work on DNA, Franklin led pioneering work on the tobacco mosaic virus and the polio virus. She died in 1958 at the age of 37 of ovarian cancer.

Franklin was born in Notting Hill, London, into an affluent and influential British Jewish family. Her father was Ellis Arthur Franklin (1894–1964), a politically liberal London banker who taught at the city's Working Men's College, and her mother was Muriel Frances Waley (1894–1976). Rosalind was the elder daughter, and the second child in the family of five children. Her father's uncle was Herbert Samuel (later Viscount Samuel), who was the Home Secretary in 1916 and the first practising Jew to serve in the British Cabinet. Her aunt, Helen Caroline Franklin, was married to Norman de Mattos Bentwich, who was the Attorney General in the British Mandate of Palestine. She was active in trade union organisation and the women's suffrage movement, and was later a member of the London County Council. Franklin herself later became an agnostic. Her uncle, Hugh Franklin was another prominent figure in the suffrage movement, although his actions embarrassed the Franklin family. From early childhood, Franklin showed exceptional scholastic abilities. She was educated at St Paul's Girls' School where she excelled in science, Latin and sports. Her family was actively involved with a Working Men's College, where her father taught electricity, magnetism, and the history of the Great War in the evenings and later became the vice-principal. Later Franklin's family helped settle Jewish refugees from Europe who had escaped the Nazis. Franklin went up to Newnham College, Cambridge, in 1938 and studied chemistry within the Natural Sciences Tripos. One of the demonstrators who taught her was the spectroscopist W.C. Price. Later, he was one of her senior colleagues at King's College. In 1941 she was awarded Second Class Honours in her Finals. This was accepted as a bachelor's degree in the qualifications for employment. Cambridge started to award the titular B.A. and M.A. to women in 1947, and the previous women graduates received these retroactively. Franklin was awarded a research fellowship and, according to an entry on the web site of the Dolan DNA Learning Center of the Cold Spring Harbor Laboratory, "She spent a year in R.G.W. Norrish's lab without great success." Resigning from Norrish's Lab, Franklin fulfilled the requirements of the National Service Act by working as an Assistant Research Officer at the British Coal Utilisation Research Association (BCURA). The BCURA was located on the Coombe Springs Estate, near Kingston upon Thames on the southwestern outskirts of London. Professor Norrish was a wartime advisor to BCURA. John G. Bennett was the Director. Marcello Pirani and Victor Goldschmidt, both refugees from the Nazis, were consultants and lectured at BCURA while Franklin was there. She studied the porosity of coal, comparing its density to that of helium. Through this, she discovered the relationship between the fine constrictions in the pores in coals and the permeability of the pore space. By concluding that substances were expelled in order of molecular size as temperature increased, Franklin helped classify coals and accurately predict their performance for fuel purposes and in the production of wartime devices (i.e. gas masks). This work was the basis of her Ph.D. thesis The physical chemistry of solid organic colloids with special reference to coal for which Cambridge University awarded her a Ph.D. in 1945. It was also the basis of several papers. The French scientist Adrienne Weill was one of Franklin's tutors at Newnham. At the end of the war, according to Anne Sayre, author of Rosalind Franklin and DNA, Franklin asked Weill 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 comprise the major part of the scientific research laboratories supported by the French government. This led to Franklin's appointment with Jacques Mering at the Laboratoire Central des Services Chimiques de l'Etat 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. He taught her the practical aspects of applying X-ray crystallography to amorphous substances. This presented new challenges in the conduct of experiments and the interpretation of results. Franklin applied them to further problems related to coal, in particular the changes to the arrangement of atoms when it is converted to graphite. Franklin published several further papers on this work. It became part of the mainstream of work on the physics and chemistry of coal, covered by a current monograph, the annual and other publications. Mering also continued the study of carbon in various forms, using X-ray diffraction and other methods.

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 fibres 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 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 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. 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[46] 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, as "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 both forms of DNA were 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, 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). 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.

Source: Wikipedia