What rosalind franklin truly contributed to the discovery of dna’s structure

What rosalind franklin truly contributed to the discovery of dna’s structure

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James Watson and Francis Crick are two of the twentieth century’s most renowned scientists. The seminal paper from the pair at the University of Cambridge, UK, detailing the discovery of the


DNA double helix, was published as part of a trio in _Nature_ 70 years ago this week1–3. They are also widely believed to have hit on the structure only after stealing data from Rosalind


Franklin, a physical chemist working at King’s College London. Lore has it that the decisive insight for the double helix came when Watson was shown an X-ray image of DNA taken by Franklin —


without her permission or knowledge. Known as Photograph 51, this image is treated as the philosopher’s stone of molecular biology, the key to the ‘secret of life’ (not to mention a Nobel


prize). In this telling, Franklin, who died of ovarian cancer in 1958 at just 37, is portrayed as a brilliant scientist, but one who was ultimately unable to decipher what her own data were


telling her about DNA. She supposedly sat on the image for months without realizing its significance, only for Watson to understand it at a glance. This version of events has entered into


popular culture. It is the subject of _Photograph 51_, a play by Anna Ziegler that starred Nicole Kidman on the London stage in 2015. The image graces a British 50 pence coin that marked the


centenary of Franklin’s birth, in 2020. The whole affair has provided fodder for scornful Twitter jokes (“What did Watson and Crick discover in 1953? Franklin’s data.”) and even a


marvellous rap battle by seventh-grade students in Oakland, California. But this is not what happened. How Rosalind Franklin was let down by DNA’s dysfunctional team One of us (N.C.) is


writing a biography of Watson, the other (M.C.) is writing one of Crick. In 2022, we visited Franklin’s archive at Churchill College in Cambridge, UK, and went through her notes together,


reconstructing the development of her ideas. We also found a hitherto unstudied draft news article from 1953, written in consultation with Franklin and meant for _Time_, a US magazine with


international reach — as well as an overlooked letter from one of Franklin’s colleagues to Crick. Together, these documents suggest a different account of the discovery of the double helix.


Franklin did not fail to grasp the structure of DNA. She was an equal contributor to solving it. Getting Franklin’s story right is crucial, because she has become a role model for women


going into science. She was up against not just the routine sexism of the day, but also more subtle forms embedded in science — some of which are still present today. FRANKLIN AND DNA In the


early 1950s, the structure and function of DNA remained unclear. It had been found in every cell type investigated, and was known to consist of a phosphate backbone to which were attached


four kinds of base — adenine, thymine, cytosine and guanine (A, T, C and G). In 1944, the microbiologist Oswald Avery and his colleagues had shown that DNA (not protein) could transform


benign _Streptococcus pneumoniae_ bacteria into a virulent form4. But it remained far from clear that it was the genetic material in all organisms. At King’s College London, biophysicists


funded by the Medical Research Council (MRC), and led by John Randall, with Maurice Wilkins as his deputy (who would later share the Nobel prize with Watson and Crick in 1962), were using


X-ray diffraction to study the structure of the molecule. In 1951, they were joined by Franklin, who had been using this technique to investigate the structure of coal at the Central State


Laboratory of Chemical Services in Paris. As is well known, Franklin and Wilkins clashed, in both personality and scientific approach. Although Franklin relished a good argument and was


determined to make progress, Wilkins abhorred confrontation and was slower to act. To ease tensions, Randall divvied up the DNA work. In what Wilkins later called a bad bargain for himself,


he agreed to turn over to Franklin the small supply of very pure DNA that he had obtained from the Swiss chemist Rudolf Signer. Wilkins was stuck with poorer quality stuff from the Austrian


biochemist Erwin Chargaff, at Columbia University in New York City. With the Signer DNA, Franklin was able to exploit a discovery that Wilkins had made earlier — DNA in solution could take


two forms, what she called the crystalline or A form, and the paracrystalline or B form. Franklin found that she could convert A into B simply by raising the relative humidity in the


specimen chamber; lowering it again restored the crystalline A form. Franklin focused on the A form, Wilkins on the B form. To a physical chemist, the crystalline form seemed the obvious


choice. When bombarded with X-rays in front of a photographic plate, it yielded sharp, detailed diffraction patterns. More detail meant more data, which meant a more accurate, albeit more


difficult analysis. The B form, by contrast, yielded patterns that were blurrier and less detailed, but simpler to analyse. Initially, Franklin understood both A and B as helical. In notes


for a seminar she gave in November 1951, she described them collectively: “big helix with several chains, phosphates on outside, phosphate–phosphate interhelical bonds, disrupted by water”5.


Unable to resolve the A-form structure, Franklin had decided by the middle of 1952 that it was not actually helical — she even teased Wilkins with a mock funeral notice for the crystalline


DNA helix6. She was not alone in being thrown off by the A-form data: after the double-helix paper1 had been published, Crick wrote of Franklin’s precise but complex, data-rich A-form image,


“I am glad I didn’t see it earlier, as it would have worried me considerably”7. The double helix and the ‘wronged heroine’ As for the B form, she and everyone else at King’s recognized that


it was some kind of helix. But to Franklin it was a distraction. At high humidity, water molecules crowded the atoms in DNA, producing a structure she described as “swollen”, “distended”,


disordered. “Anyway,” she wrote in the notes for her 1951 seminar, under increased humidity, “the stuff ultimately dissolves, i.e. chains are separated from one another by water”5. She saw


the B form as an artefact of being water-logged, a symptom of the loss of crystalline order — hence “paracrystalline”. This explains why, in late 1952 and early 1953, she rejected the


argument that DNA was intrinsically helical. From a chemist’s perspective, Franklin’s decision to focus on the crystalline A form was perfectly logical, as were the conclusions she drew from


analysing it. But her focus on the drier A form ignored the very wet reality of the inside of a cell — which would mean that DNA took the more humid B form. Together with her insistence


that the diffraction data be fully analysed before any modelling was attempted, it would hamper Franklin’s efforts for more than a year. THE MEANING OF PHOTOGRAPH 51 Even Franklin’s


advocates often unwittingly perpetuate a caricatured view of her science — one that can be traced back to Watson’s reality-distorting 1968 bestseller, _The Double Helix_8. Watson’s version


of the next, crucial stage in the story is often repeated to highlight how Franklin was deprived of due credit. Inadvertently, this undermines her. According to Watson, in early 1953, he


visited King’s and got into a row with Franklin. Wilkins, he wrote, rescued him from the confrontation and then showed him Photograph 51, a particularly clear image of the B form, taken 8


months earlier by Franklin and her graduate student Raymond Gosling. Franklin had put the photograph aside to concentrate on the A form. She was preparing to transfer to Birkbeck College,


also in London, and had been instructed to leave her DNA work behind. Gosling was now being supervised by Wilkins, and he had given Wilkins the photograph. (He says he did so with Franklin’s


knowledge9.) The image, Watson claimed in _The Double Helix_, showed that a DNA helix “must exist” — only a helical structure could produce those marks8. Because of Watson’s narrative,


people have made a fetish of Photograph 51. It has become the emblem of both Franklin’s achievement and her mistreatment. But Watson’s narrative contains an absurd presumption. It implies


that Franklin, the skilled chemist, could not understand her own data, whereas he, a crystallographic novice, apprehended it immediately. Moreover, everyone, even Watson, knew it was


impossible to deduce any precise structure from a single photograph — other structures could have produced the same diffraction pattern. Without careful measurements — which Watson has


insisted he did not make — all the image revealed was that the B form was probably some kind of helix, which no one doubted. Furthermore, various lines of evidence — including _The Double


Helix_ itself, read carefully — show that it played little, if any, part in Watson and Crick’s inching towards the correct structure between January and March 1953. In fact, it was other


data from Franklin and Wilkins that proved crucial, and even then, what really happened was less malicious than is widely assumed. Watson did get a jolt from seeing the photograph — because


of when he saw it. Just days before, the Cambridge group had received a manuscript from the US chemist Linus Pauling, in which he’d claimed to have solved the DNA structure. Although Pauling


had made some elementary errors, Lawrence Bragg, head of the Cavendish Laboratory, who had a long-standing rivalry with Pauling, had encouraged Watson and Crick to resume their model


building. Watson had dropped in at King’s to show off Pauling’s blunder, and Wilkins had shown him the photograph. Fashioning that moment into the climax of _The Double Helix_ was a literary


device: a classic eureka moment, easy for lay readers to understand. From 1951, Wilkins had kept Watson and Crick abreast of his work on the B form, in particular his belief that the


structure contained one or more helices, repeated every 34 angstroms, and he might have said that within each repeat there were probably 10 elements. Shortly after Watson saw Photograph 51,


Crick’s supervisor, Max Perutz, handed them an informal report of the activity of the King’s MRC unit, which he had been given as part of an official visit to the unit in December 1952. This


included a page from Franklin, describing her work. In a 1969 letter to _Science_, although Perutz said that he regretted sharing the report without first consulting the King’s group, it


was not confidential10. Indeed, a letter we have discovered from a King’s researcher, Pauline Cowan, written to Crick in January 1953, invites Crick to a talk by Franklin and Gosling, who,


Cowan continues, “say that it is mostly for a non-crystallographic audience + that Perutz already knows more about it than they are likely to get across so you may not think it worthwhile


coming”. Thus, Franklin seems to have assumed that Perutz would share his knowledge with Crick as part of the usual informal scientific exchange11. In her contribution to the MRC report,


Franklin had confirmed the 34 Å result for the B form. She also reported that the unit cell (the repeating unit of the crystal) of DNA was huge; it contained a larger number of atoms than


any other unit cell in any other known molecular structure. Franklin also added some key crystallographic data for the A form, indicating that it had a ‘C2’ symmetry, which in turn implied


that the molecule had an even number of sugar-phosphate strands running in opposite directions. Notes by Crick for a lecture on the history of the double helix, given to historians of


science at the University of Oxford in May 1961, together with formal and informal remarks made throughout his life, reveal that, unlike Photograph 51, this report was truly significant for


confirming the structure that Watson and Crick eventually obtained. In the end, however, neither Photograph 51 nor the MRC report ‘gave’ Watson and Crick the double helix. What did was six


weeks of what they later described as “trial and error” — making chemical calculations and fiddling about with cardboard models. (Watson made this plain in _The Double Helix_; Crick did so


in a series of interviews with the historian Robert Olby in the late 1960s and early 1970s.) Franklin’s data and Watson and Crick’s many conversations with Wilkins had provided what seem


like key pieces of information — the phosphate groups were on the outside of the molecule; there was a repeat every 34 Å; perhaps there were ten bases per repeat and an even number of


strands running in opposite directions (the implication of the C2 symmetry). Yet, according to their own accounts, the pair ignored every one of these facts at one point or another during


those six weeks. Once they had hit on a conceptual model of the structure, the MRC report provided a valuable check on their assumptions. So it was not a case of them stealing the King’s


group’s data and then, voila, those data gave them the structure of DNA. Instead, they solved the structure through their own iterative approach and then used the King’s data — without


permission — to confirm it. WHAT FRANKLIN REALLY DID Franklin contributed several key insights to the discovery of the double helix. She clearly differentiated the A and B forms, solving a


problem that had confused previous researchers. (X-ray diffraction experiments in the 1930s had inadvertently used a mixture of the A and B forms of DNA, yielding muddy patterns that were


impossible to fully resolve.) Her measurements told her that the DNA unit cell was enormous; she also determined the C2 symmetry exhibited by that unit cell12. The C2 symmetry was one of 230


types of crystallographic 3D ‘space groups’ that had been established by the end of the nineteenth century. Franklin failed to appreciate its significance not because she was obtuse, but


because she was unfamiliar with it. According to her colleague Aaron Klug, Franklin later said that she “could have kicked herself” for not realizing the structural implications13. Crick did


realize the implications because he happened to have studied C2 symmetry intensely. But even he did not use Franklin’s determination of this symmetry when building the model; rather, it


provided a powerful corroboration when their model was complete. ENJOYING OUR LATEST CONTENT? LOGIN OR CREATE AN ACCOUNT TO CONTINUE * Access the most recent journalism from Nature's


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