Fantastic Women Series l Rosalind Franklin l DNA Pioneer

Photo 51

This is an X-ray based fiber diffraction image of a paracrystalline gel composed of DNA fiber taken by Rosalind Franklin and her graduate student Raymond Gosling, in May 1952 at King’s College London, in the basement underneath the chemistry laboratories at the MRC Biophysics Unit. Franklin, a biophysicist, had been recruited to the unit to work on the structure of DNA.

The image was tagged “photo 51” because it was the 51st diffraction photograph that Franklin had taken. It was critical evidence in identifying the structure of DNA.

Photo 51 changed biology forever, because it showed us what DNA looked like.

Rosalind Franklin

Rosalind Elsie Franklin was a British chemist and X-ray crystallographer. Her work was central to understanding the molecular structure of DNA (deoxyribonucleic acid), RNA (ribonucleic acid), viruses, coal, and graphite.

She was born on July 25, 1920, into an affluent and influential British Jewish family, and went on to graduate with degree in natural sciences from Cambridge in 1941. During her final year, 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 also helped her to improve her French.

Franklin then joined the physical chemistry laboratory of the University of Cambridge to work for a PhD. under Ronald George Wreyford Norrish, who later won the Nobel Prize in Chemistry. However, disappointed with Norrish’s work ethic and lack of enthusiasm, she resigned and took up a research position under the British Coal Utilisation Research Association (BCURA) in 1942. Her research on coal there helped her to earn her PhD from Cambridge in 1945.

Franklin then moved to Paris for her postdoctoral research at the Laboratoire Central des Services Chimiques de l’État, she became not only an accomplished, but a famous X-ray crystallographer.

Franklin subsequently joined King’s College London as a research associate in 1951, where biophysicists, including director John Randall and his deputy Maurice Wilkins, were funded by the Medical Research Council (MRC). They were using X-ray diffraction to study the structure of the molecule. Rosalind, meanwhile, had been using the same technique to investigate the structure of coal at the Central State Laboratory of Chemical Services in Paris. It was at this time, she discovered key properties of DNA that helped to eventually define its structure.

While she was originally appointed to work on X-ray diffraction of proteins and lipids in solution, the director John Randall redirected her to work on DNA fibres, an emerging and popular field at this 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. Randall however, had done this without informing either Wilkins or Gosling. In fact, he made the reassignments when Wilkins was away on holiday!

Wilkins and Gosling had obtained a good-quality diffraction picture of a highly purified DNA sample, prepared, and widely shared by Swiss chemist Rudolf Signer. When Wilkins returned from holiday, he had to hand over the Signer DNA and Gosling to Franklin. This was the background behind the famous friction that developed between Franklin and Wilkins.

Franklin continued her work and together with Gosling, she applied her expertise in X-ray diffraction techniques to the structure of DNA. She refined, adjusted, and focussed a new fine-focus X-ray tube and microcamera, that had been ordered by Wilkins. Her physical chemistry background enabled her to apply a critical innovation to the camera, so that the humidity inside its chamber could be controlled.

Wilkins asked her about this, and her answer offended him because he felt that she had “an air of cool superiority”. Their personality clash had begun.

With the innovative humidity-controlling camera, Franklin was soon able to produce X-ray images of better quality than those of Wilkins. She discovered that the DNA sample could exist in two forms: at a relative humidity higher than 75%, the DNA fibre became long and thin (B form); when it was drier, it became short and fat (A form). At this time Rosalind considered both A and B form as helical

When she presented this data at a lecture in November 1951, in King’s College London, Franklin wrote the following in her lecture notes: “The results suggest a helical structure (which must be very closely packed) containing 2, 3 or 4 co-axial nucleic acid chains per helical unit and having the phosphate groups near the outside”. She described them collectively as “big helix with several chains, phosphates on outside, phosphate–phosphate interhelical bonds, disrupted by water”.

In November 1951, James Watson and Francis Crick at the Cavendish Laboratory in Cambridge University had started to build a molecular model of one sample of DNA, using data like that available to both teams at King’s.

By this time the conflict between Franklin and Wilkins was developing even further and so each of them were assigned one form of the DNA sample that she had identified. Franklin worked on the A form and Wilkins on B form. The A or crystalline form, when bombarded with X-rays, produced detailed diffraction patterns, which meant more data and more accurate but more difficult analysis. The B form on the other hand, produced blurrier photos, but was easier to analyse.

Franklin and Gosling continued to work on the X-ray pictures that they had produced and in May 1952, Gosling took Photo 51, the famous photo of the DNA double helix structure. Although by the end of 1951, it was generally accepted that DNA was a helix, it was Photo 51 that confirmed its double helix structure.

The X-ray diffraction pictures, including the landmark Photo 51 taken by Gosling, have been called by John Desmond Bernal as “amongst the most beautiful X-ray photographs of any substance ever taken”.

Due to disagreements with her director, John Randall, and her ongoing conflict with Maurice Wilkins, Franklin moved to Birkbeck College in 1953, but she had to leave behind all her DNA work at King’s College. Wilkins was given copies of Franklin’s diffraction photographs by Gosling, as well as her notes.

By this time, Watson and Crick had finished building their model on 7 March 1953, a day before they received a letter from Wilkins stating that Franklin was finally leaving. Now they could corroborate their model with the data from the X-ray photographs.

Although Franklin had earlier considered the second sample (the B Form that was given to Wilkins to work upon) was not a helix, she had later conceded that it was. Examination of the original draft of one of her manuscripts dated 17 March 1953, clearly showed that Franklin had already resolved the correct structure. While her conclusion on the helical nature was evident, she had been unable to understand the complete organisation of the DNA strands. The possibility of two strands running in opposite directions did not occur to her. Franklin was very methodical and wanted far greater evidence before she would announce anything or publish a model.

However, Francis and Crick had by now completed their model and this news went around like wildfire. Franklin asked permission to see their model and her cautious nature meant that she retained her scepticism for premature model building even after seeing the Watson–Crick model and remained unimpressed. She is reported to have commented, “It’s very pretty, but how are they going to prove it?”

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”. These were all the notes and manuscripts available at King’s College, including Rosalind’s work that she left behind.

So, although her works on coal and viruses were appreciated in her lifetime, Franklin’s contributions to the discovery of the structure of DNA were largely unrecognized during her life. Not only was she dealing with the sexism rampant during her time in general, she also most certainly must have had to deal with the institutionalised sexism within the scientific community.

The story that has come down to us is from Watson’s account in The Double Helix, where he says that he was presented with Photo 51 by Wilkins when Watson visited King’s College in early 1953. He had apparently got into a confrontation with Franklin, was then rescued by Wilkins, who then showed him the photo. According to this narrative, Franklin had put aside Photo 51 to concentrate on the A form of DNA, so basically, she had ignored it. Watson said in The Double Helix, that this image showed him that the DNA is a helix. This muted acknowledgement of her work was buried under descriptions of Watson’s (often quite negative) regard towards Franklin during the period of their work on DNA.

The discovery of the double helix got Francis Crick, James Watson, and Maurice Wilkins the Nobel Prize in Physiology or Medicine in 1962. When Franklin died in 1958, the DNA structure was not considered to be fully proven. It took them another seven years to collect enough data to prove and refine the proposed DNA structure. Franklin and Wilkins work (including Photo 51) helped them to confirm it.

Franklin’s work contributed immensely to the discovery of the double helix, among other things, differentiating the A and B forms, as well as how DNA could specify proteins. She just did not come to the final conclusions and Watson and Crick beat her to the answer.

According to Watson, Franklin could ideally have been awarded a Nobel Prize in Chemistry, together with Wilkins but this was not possible because at that time the rule was that a Nobel prize could not be awarded posthumously, unless the nomination had been made for a then-alive candidate before February 1st of the award year.

There is no doubt that Franklin’s experimental data were used by Crick and Watson to confirm and build their model of DNA in 1953. Franklin was not acknowledged and perhaps that was due to the fact it would have been very difficult to cite the King’s College unpublished work from the report they had seen. Any acknowledgment they gave her was always muted and always in conjunction with Wilkins. She should have been acknowledged and her King’s college MRC data should have been obtained with permission (it was not). They did try to set the record straight by admitting in a paper published in 1954 that without Franklin’s data, “the formulation of our structure would have been most unlikely, if not impossible”.

The bottom line is that they ALL worked on and contributed to the understanding of the structure of the DNA. Rosalind Franklin just did not get all the credit she deserved.

At Birkbeck College, working under John Desmond Bernal, Franklin led pioneering work on the molecular structures of viruses.

On the day before she was to unveil the structure of tobacco mosaic virus (TMV) at an international fair in Brussels, Franklin 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. She also continued to explore another major nucleic acid, RNA, a molecule equally central to life as DNA. She again used X-ray crystallography to study the structure of the tobacco mosaic virus, which is an RNA virus, and started the work to study the polio virus.

Aaron Klug, Franklin’s colleague, and principal beneficiary in her will, was the sole winner of the Nobel Prize in Chemistry 1982, “for his development of crystallographic electron microscopy and his structural elucidation of biologically important nucleic acid-protein complexes”. This work was exactly what Franklin had started and which she introduced to Klug. It is possible that were she alive, Franklin would have shared that Nobel Prize.

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