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By the time I came to Cambridge, Francis’s forte was increasingly seen to be crystallographic theory, though his early forays in the field had not been universally appreciated. At his first group seminar in July 1950, entitled “The Theory of Protein Crystallography,” he came to the conclusion that the methodologies currently used by Perutz and Kendrew could never establish the three-dimensional structure of proteins–an admittedly impolitic assertion that caused Sir ­Lawrence Bragg to brand Crick a boat rocker. Much more harm came a year later when Bragg presented his newest brainchild and Francis told him how similar it was to one he himself had presented at a meeting six months earlier. After the infuriating implication of his being an idea snatcher, Sir ­Lawrence called ­Francis into his office to tell him that once his thesis was completed he would have no future at the ­Cavendish. Fortunately for me, and even more so for Francis, Cambridge was unlikely to grant him the degree for another 18 to 24 months.

I was by then having lunch with Francis almost daily at the nearby pub, the Eagle, which during the war was favored by American airmen flying out of nearby airfields. Soon we would be upgraded from desks beside our lab benches to a largish office of our own next to the connected pair of smaller rooms used by Max and John. There, Francis’s ever irrepressible laughter would less disturb the work habits of other unit members. At our first meeting, Francis had spoken of his much valued friend Maurice Wilkins, who, like him, had made a wartime marriage that soon disintegrated with peace. Because he was curious to know whether Maurice’s crystallography had generated any new, perhaps sharper x-ray photos from DNA, Francis invited him for a Sunday dinner at the Green Door, the tiny apartment on top of a tobacconist shop on ­Thompson Lane, across from St. John’s College. Earlier occupied by Max Perutz and his wife Gisela, it had been home to Francis and his second wife Odile since their marriage two years before in August 1949.

At that meal, we learned of an unexpected complication to Maurice’s pursuit of DNA. While he was on an extended winter visit to the United States, his boss, Professor J. T. Randall, had recruited to the King’s DNA effort the Cambridge-trained physical chemist Rosalind Franklin. For the past four years she had been using x-rays in Paris to investigate the properties of carbon. Rosalind understood from ­Randall’s description of her responsibilities that x-ray analysis of DNA was to be her responsibility solely. This effectively blocked Maurice’s further x-ray pursuit of his crystalline DNA. Though not formally trained as a crystallographer, Maurice had already mastered many procedures and had much to offer. But ­Rosalind didn’t want a collaborator; all she wanted from ­Maurice was the help of his research student Raymond ­Gosling. Now, though out in the cold for two months, ­Maurice could not stop thinking about DNA. He believed his past x-ray pattern did not arise from single ­polynucleotide chains but from helical assemblies of either two or three intertwined chains bonded to each other in a fashion as yet to be determined. With the DNA ball sadly no longer under his control, Maurice suggested that if Francis and I wanted to learn more we should go to King’s in a month’s time, November 21, to hear ­Rosalind give a talk.

Before it was time to go to London, Francis had reason to feel good about his place in the Cavendish. He and the clever crystallographer Bill Cochran derived easy-to-use mathematical equations for how helical molecules diffract x-rays. Each of them, in fact, did so independently within 24 hours of being shown by Bragg a manuscript from Vladimir Vand in Glasgow, whose equations they immediately saw as only half baked. Theirs was an important achievement, for ­Francis and Bill had given the world the equations that could predict the diffraction patterns of helices according to specific dimensions. The next spring I was to deploy them to show that the protein subunits of Tobacco Mosaic Virus are helically arranged.

The best way to reveal DNA’s 3-D structure might well then have been through building molecular models using Cochran and Crick’s equations. Until a year before, this approach had made no sense, since the nature of the covalent bonds linking nucleotides to each other in DNA chains was unknown. But after work by Alex Todd’s nearby research group in the Chemical Laboratory at Cambridge, it was clear that DNA’s nucleotides are held together by 3’-5’ phosphodiester bonds. A focus on model building was a way to set oneself apart from the alternative approach of focusing on x-ray photograph details being pursued at King’s College in London.

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Credit: Andreas Feininger/Time-Life Pictures/Getty Images

Tagged: Biomedicine

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