Franklin, Rosalind, 1920-1958

Rosalind Elsie Franklin (25 July 1920 – 16 April 1958)[1] was an English chemist and X-ray crystallographer whose work was central to the understanding of the molecular structures of DNA (deoxyribonucleic acid), RNA (ribonucleic acid), viruses, coal, and graphite.[2] Although her works on coal and viruses were appreciated in her lifetime, her contributions to the discovery of the structure of DNA were largely unrecognized during her life, for which she has been variously referred to as the "wronged heroine",[3] the "dark lady of DNA",[4] the "forgotten heroine",[5] a "feminist icon",[6] and the "Sylvia Plath of molecular biology".[7]

She graduated in 1941 with a degree in natural sciences from Newnham College, Cambridge, and then enrolled for a PhD in physical chemistry under Ronald George Wreyford Norrish, the 1920 Chair of Physical Chemistry at the University of Cambridge. Disappointed by Norrish's lack of enthusiasm,[8] she took up a research position under the British Coal Utilisation Research Association (BCURA) in 1942. The research on coal helped her earn a PhD from Cambridge in 1945.[9] Moving to Paris in 1947 as a chercheur (postdoctoral researcher) under Jacques Mering at the Laboratoire Central des Services Chimiques de l'État, she became an accomplished X-ray crystallographer. After joining King's College London in 1951 as a research associate, she discovered the key properties of DNA, which eventually facilitated the correct description of the double helix structure of DNA.[3] Owing to disagreement with her director, John Randall, and her colleague Maurice Wilkins, she was compelled to move to Birkbeck College in 1953.

Franklin is best known for her work on the X-ray diffraction images of DNA while at King's College London, particularly Photo 51, taken by her student Raymond Gosling, which led to the discovery of the DNA double helix for which Francis Crick, James Watson, and Maurice Wilkins shared the Nobel Prize in Physiology or Medicine in 1962.[10][11] Watson suggested that Franklin would have ideally been awarded a Nobel Prize in Chemistry, along with Wilkins but, although there was not yet a rule against posthumous awards,[12] the Nobel Committee generally did not make posthumous nominations.[13][14]

Working under John Desmond Bernal, Franklin led pioneering work at Birkbeck on the molecular structures of viruses.[15] On the day before she was to unveil the structure of tobacco mosaic virus at an international fair in Brussels, she died of ovarian cancer at the age of 37 in 1958. Her team member Aaron Klug continued her research, winning the Nobel Prize in Chemistry in 1982.

Franklin was born on 25 July 1920 in 50 Chepstow Villas,[16] Notting Hill, London, into an affluent and influential British Jewish family.

Franklin's father was Ellis Arthur Franklin (1894–1964), a politically liberal London merchant 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. David (1919–1986) was the eldest brother; Colin (1923–2020), Roland (born 1926), and Jenifer (born 1929) were her younger siblings.[19]

Franklin's paternal great-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.[20] Her aunt, Helen Caroline Franklin, known in the family as Mamie, was married to Norman de Mattos Bentwich, who was the Attorney General in the British Mandate of Palestine.[21] Helen was active in trade union organisation and the women's suffrage movement and was later a member of the London County Council.[22][23] Franklin's uncle, Hugh Franklin, was another prominent figure in the suffrage movement, although his actions therein embarrassed the Franklin family. Rosalind's middle name, "Elsie", was in memory of Hugh's first wife, who died in the 1918 flu pandemic.[19] Her family was actively involved with the Working Men's College, where her father taught the subjects of electricity, magnetism, and the history of the Great War in the evenings, later becoming the vice principal.[24][25]

Franklin's parents helped settle Jewish refugees from Europe who had escaped the Nazis, particularly those from the Kindertransport.[26] They took in two Jewish children to their home, and one of them, a nine-year-old Austrian, Evi Eisenstädter, shared Jenifer's room.[27] (Evi's father Hans Mathias Eisenstädter had been imprisoned in Buchenwald, and after liberation, the family adopted the surname "Ellis".)

Franklin went to Newnham College, Cambridge, in 1938 and studied chemistry within the Natural Sciences Tripos. There she met the spectroscopist Bill Price, who worked with her as a laboratory demonstrator and who later became one of her senior colleagues at King's College London.[39] In 1941, she was awarded second-class honours from her final exams. The distinction was accepted as a bachelor's degree in qualifications for employment. Cambridge began awarding titular BA and MA degrees to women from 1947, and the previous women graduates retroactively received these.[40] In her last year at Cambridge, she met a French refugee Adrienne Weill, a former student of Marie Curie, who had a huge influence on her life and career and who helped her to improve her conversational French.[41][42]

Franklin was awarded a research fellowship at Newnham College, with which she joined the physical chemistry laboratory of the University of Cambridge to work under Ronald George Wreyford Norrish, who later won the Nobel Prize in Chemistry. In her one year of work there, she did not have much success.[43] As described by his biographer, Norrish was "obstinate and almost perverse in argument, overbearing and sensitive to criticism".[44] He could not decide upon the assignment of work for her. At that time he was succumbing to heavy drinking. Franklin wrote that he made her despise him completely.[45] Resigning from Norrish's Lab, she fulfilled the requirements of the National Service Acts by working as an assistant research officer at the British Coal Utilisation Research Association (BCURA) in 1942.[15] The BCURA was located on the Coombe Springs Estate near Kingston upon Thames near the southwestern boundary of London. Norrish acted as advisor to the military at 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 worked there.[2] During her BCURA research, she initially stayed at Adrienne Weill's boarding house in Cambridge until her cousin, Irene Franklin, proposed that they share living quarters at a vacated house in Putney that belonged to her uncle. With Irene, she volunteered as an Air Raid Warden and regularly made patrols to see the welfare of people during air raids.[46]

She studied the porosity of coal using helium to determine its density.[47] Through this, she discovered the relationship between the fine constrictions in the pores of coals and the permeability of the porous space. By concluding that substances were expelled in order of molecular size as temperature increased, she helped classify coals and accurately predict their performance for fuel purposes and for production of wartime devices such as gas masks.[48] This work was the basis of her PhD thesis The physical chemistry of solid organic colloids with special reference to coal for which the University of Cambridge awarded her a PhD in 1945.[9] It was also the basis of several papers.[2]

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 her 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 her appointment with Jacques Mering at the Laboratoire Central des Services Chimiques de l'État in Paris. She joined the labo (as referred to by the staff) of Mering on 14 February 1947 as one of the fifteen chercheurs (researchers).[49][50]

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.[2] 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 and to other carbonaceous materials, in particular the changes to the arrangement of atoms when these are converted to graphite.[2] She published several further papers on this work which has become part of the mainstream of the physics and chemistry of coal and carbon. She coined the terms graphitising and non-graphitising carbon. The coal work was covered in a 1993 monograph,[51] and in the regularly-published textbook Chemistry and Physics of Carbon.[52] Mering continued the study of carbon in various forms, using X-ray diffraction and other methods.[53]

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.[54] She was originally appointed to work on X-ray diffraction of proteins and lipids in solution, but Randall redirected her work to DNA fibres[55] because of new developments in the field, and she was to be the only experienced experimental diffraction researcher at King's at the time.[56][57] 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.[58]Franklin, now working with Gosling,[64] 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 she applied was making the camera chamber that could be controlled for its humidity using different saturated salt solutions.[62] When Wilkins inquired about this improved technique, she replied in terms which offended him as she had "an air of cool superiority".[65]

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.[66] 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."[62]

In February 1953, 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 1952 that DNA was helical with either two or three stands, they constructed a triple helix model, which was immediately proven to be flawed.[62] Franklin's research was completed by February 1953, ahead of her move to Birkbeck, and her data was critical.[82] Model building had been applied successfully in the elucidation of the structure of the alpha helix by Linus Pauling in 1951,[71][83] 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.[72][84] Her conviction was justified by the fact that Pauling and Corey also came up in the late 1952 (published in February 1953[85]) with an erroneous triple helix model.[74]

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.[86]

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".[87] However, they knew they must complete their model before they could be certain.[88]

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".[89] 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.[90]

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.[67] But he later discovered the original draft of the manuscript (dated 17 March 1953) from which it became clear that Franklin had already resolved the correct structure. The news of Watson–Crick model reached King's the next day, 18 March,[75] suggesting that Franklin would have learned of it much later since she had moved to Birkbeck. Further scrutiny of her notebook revealed that Franklin had already thought of the helical structure for B-DNA in February 1953 but was not sure of the number of strands, as she wrote: "Evidence for 2-chain (or 1-chain helix)."[91] Her conclusion on the helical nature was evident, though she failed to understand the complete organisation of the DNA strands as the possibility two strands running in opposite directions did not occur to her.[75]

Towards the end of February she began to work out the indications of double strands, as she noted: "Structure B does not fit single helical theory, even for low layer-lines." It soon dawned to her that the B-DNA and A-DNA were structurally similar,[91] and perceived A-DNA as an "unwound version" of B-DNA.[75] She and Gosling wrote a five-paged manuscript on 17 March titled "A Note on Molecular Configuration of Sodium Thymonucleate."[92] 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,[75] and appeared as such in the trio of 25 April 1953 Nature articles; the other modification being a deletion of "A Note on" from the title.[93][94]