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Preoccupied much of the fall of 1952 with the race against Francis Crick for the coiled-coil structure of alpha keratin, Pauling only turned to DNA in earnest in late November. Soon he was very much attracted to a DNA model in which three sugar-phosphate backbones coiled around each other. He was hung up on three chains because of the reported high density of DNA. At no time did he seriously consider a two-chain molecule. For the three chains to hold together, he reasoned, DNA would have to be uncharged, forming hydrogen bonds between opposing phosphate groups. Soon satisfied that he had found the general structure for nucleic acids, he wrote to Alex Todd a week before Christmas adding that he was not bothered that his structure provided no clues as to how DNA functions in cells. That problem was for another day. At no time did he ever take into account ­Chargaff’s base compositions, published more than a year before in several journals. The essential parameters for Linus that December were bond angles and length, not what DNA did biologically or how it behaved in solution. It was immediately evident that the atoms of his model were not fitting together as neatly as they did in the alpha helix. Even his best structure was stereochemically shaky, with several central phosphate oxygens uncomfortably close to each other.

Fearing that someone in England might beat him to the punch with a similar model, Linus hastily submitted a manuscript for publication in the Proceedings of the National Academy. Then he triumphantly sent two manuscript copies to Cambridge–one to Bragg, the other to his son, Peter. We were instantly engulfed in anxiety until we realized that Linus had used hydrogen atoms belonging to the phosphate groups to hydrogen-bond the three chains together. We knew at once that his model must be wrong, since DNA–an acid–normally releases all its hydrogen ions in solution. So Francis and I rushed around Cambridge to see whether the local chemical hotshots also found Pauling’s concept totally implausible. Quickly reassured by Alex Todd that Linus had indeed made a gigantic chemical goof, I went down almost immediately to London to show the manuscript to Maurice Wilkins and Rosalind Franklin, the latter preparing to move to J. D. Bernal’s group in Birkbeck College, where she would no longer work on DNA.

Maurice was more than relieved to learn that Linus was so far off base. In contrast, Rosalind was annoyed at my showing her the manuscript, tartly telling me that she had no need to read about helices. In her mind, the crystalline DNA A-form structure was most certainly not helical. In fact, six months before, she had sent out invitations to a July “memorial service” to celebrate the death of the DNA helix. Here ­Maurice thought that Rosalind had been badly deluding herself, and to prove it, he impulsively showed me an x-ray photo that the King’s group had been keeping secret since Raymond Gosling took it more than nine months before. Originating from a more hydrated B-form DNA fiber, this picture displayed unequivocally the large cross-shaped diffraction pattern to be expected from a helical molecule. My jaw dropped, and I rushed back to Cambridge to tell everyone what I had learned. I thought we should not wait a moment longer before commencing to build models. Someone was bound to tell Linus that his was dead on arrival. Sir Lawrence Bragg instantly agreed, and with him finally behind us, Francis and I soon were back playing with cutout shapes. By then I realized that DNA’s density did not, as I originally thought, rule out two strands as opposed to three. It thus made sense for me to focus first on possible ways for two DNA chains to twist around each other.

In fact, Rosalind should also have been focusing on two-chained DNA models. More than a year before, she had carefully measured her x-ray diffraction patterns from crystalline A-form DNA looking for possible molecular symmetries. Finding her data compatible with three possible chemical “space groups,” she went up to Oxford to get advice from Dorothy Hodgkin, then England’s premier crystallographer, justly famed for solving the structure of penicillin. As soon as ­Dorothy saw that Rosalind was considering space groups involving mirror symmetry, however, she sensed crystallographic callowness. Experienced crystallographers would never postulate mirror symmetry for a molecule made up exclusively of 2-deoxy-D-ribose. Instead, Dorothy believed, Rosalind should have been considering only the implications of the third monoclinic space group (a rectangular prism of three unequal axes). Upset by Dorothy’s sharp put-down of her crystallographic acumen, Rosalind left Oxford, never to return. If she had gone instead to Francis for help, she would have immediately learned that the C2 monoclinic space group suggested that DNA was a double helix with its chains running in opposite directions.

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

Tagged: Biomedicine

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