The idea behind X-ray crystallography was genius in its simplicity. Physicists had known from the beginning of the nineteenth century that if they shined visible light onto a finely spaced grating, the light that passed through formed a diffraction pattern of bright and dark spots on a screen on the other side. The bright spots marked the locations where light waves from different slits in the grating combined to enhance each other, while the dark spots formed where the different waves underwent destructive interference (as when a crest from one wave was superimposed onto a trough from another). Physicists also knew, however, that for this diffraction pattern to form, the spacings between the different slits needed to be of the same order as the wavelength of the light (the distance between two successive crests in the wave). While it was relatively easy to manufacture such fine gratings for visible light, it was impossible to produce them for X-rays, since a typical wavelength for X-rays is a few thousand times shorter than wavelengths in the visible part of the spectrum. The first person to realize that natural, periodic crystals could serve as gratings for X-ray diffraction experiments was Max von Laue. The German physicist recognized that the inter-atomic distances in crystals were precisely of the order of the presumed wavelengths of X-rays. Following in Laue’s footsteps, Lawrence Bragg formulated the mathematical law describing the diffraction of X-rays on a crystalline structure. Amazingly, he obtained this important result during his first year as a research student at Cambridge. The father and son team then went on to build the X-ray spectrometer that allowed them to analyze the structure of many crystals. Lawrence Bragg remains, by the way, the youngest person to be awarded a Nobel Prize. (He won it at age twenty-five!)

Given this formidable legacy, we can imagine that when Pauling saw the title of the paper by Bragg, Kendrew, and Perutz, his heart missed a beat. The first two paragraphs of the paper indeed gave the impression that Bragg’s team may have beaten him to the punch: “Proteins are built of long chains of amino-acid residues . . . In this paper an attempt is made to glean as much information as possible about the nature of the chain from x-ray studies of crystalline proteins, and to survey the possible types of chain which are consistent with such evidence as is available.” Pauling read quickly all thirty-seven pages and was relieved to discover that while the Cavendish researchers described some twenty structures, the alpha-helix wasn’t one of them. Moreover, they concluded that none of the examined structures was acceptable as a model for alpha keratin. Pauling agreed happily with this conclusion, especially since he thought that Bragg’s team did not apply the most important constraint to its configurations but did impose a handicap that he regarded as totally unnecessary. On one hand, none of Bragg’s models assumed the planarity of the peptide group, of whose correctness Pauling was absolutely convinced. On the other, the Cavendish team appeared to be hung up on the notion that in every full turn of its helical structures, there had to be an integer number of amino acids. Pauling’s alpha-helix broke with tradition and had about 3.6 amino acids per turn, and he saw nothing wrong with that. Coming from an X-ray crystallography background, Bragg also adhered religiously to the apparent 5.1 angstrom distance between turns suggested by Astbury’s data. Perutz later described that to start the team off, Bragg hammered nails representing amino acid residues into a broomstick in a helical pattern with an axial distance between successive turns of 5.1 centimeters.

Pauling was always extremely competitive in nature. Even though he was pleased to see that the Cambridge team had missed a few key points, the appearance of Bragg’s paper prompted him into action, for fear he might be scooped. In October 1950 he and Corey sent a short note describing the alpha-helix and the gamma-helix to the Journal of the American Chemical Society. Around the same time, some encouraging results were coming from another British research group at Courtaulds Research Laboratories. There, Clement Bamford, Arthur Elliott, and their collaborators succeeded in producing fibers of synthetic polypeptides. To Pauling’s delight, X-ray diffraction photographs of those fibers showed clearly that the repeat distance along the axis was 5.4 angstroms—consistent with Pauling’s findings—rather than 5.1 angstroms. This raised the suspicion that the latter feature in the X-ray photographs of hair could simply be an artifact produced by overlapping reflections rather than a major clue to the structure. Increasingly convinced of the truth of this interpretation, Pauling submitted a paper by himself, Corey, and Branson that contained a detailed explanation of the alpha- and gamma-helices. It was only fitting that this important paper was submitted precisely on the day of Pauling’s fiftieth birthday, February 28, 1951.

There is, incidentally, an interesting anecdote concerning the use of the term “helix,” which I heard from chemist Jack Dunitz, who at the time was a postdoctoral fellow with Pauling. Dunitz recalled that in 1950 Pauling kept using the term “spiral” to describe the structure of alpha keratin. Even in Pauling and Corey’s short communication in the Journal of the American Chemical Society, they wrote exclusively about spirals. One day, said Dunitz, he remarked to Pauling that he thought that the word “spiral” referred only to the two-dimensional, planar shape, while the three-dimensional one had to be called a “helix.” Pauling responded that a spiral could be either two-dimensional or three-dimensional, but added that on second thought, he liked the word “helix” better. When the extensive manuscript by Pauling, Corey, and Branson was submitted, it avoided the word “spiral” altogether. Its title read: “The Structure of Proteins: Two Hydrogen-Bonded Helical Configurations of the Polypeptide Chain.” Pauling was by then so confident in his model that he and Corey followed the alpha-helix paper with a barrage of papers on the folding of polypeptide chains.

That spring in England, Max Perutz went one Saturday morning to the library, and there, in the latest issue of the Proceedings of the National Academy of Sciences, he found the series of papers by Pauling. Some thirty-six years later, he described what he had experienced that morning (in a somewhat technical language, but the emotions were crystal clear):