by Thomas Hager
Through the summer and fall of 1950, through Budenz's accusations and the Caltech internal investigation, Pauling kept hammering away at that problem and outlining structures for other proteins. His sense of urgency was heightened in September 1950 when he learned that his former student (and Dorothy Wrinch confidant) David Harker was setting up an East Coast laboratory for protein structure research, with the backing of Irving Langmuir and the promise of major financial support. The competition was becoming fiercer. Pauling needed to work even harder, and to do so began using a technique he had developed for harnessing his subconscious. Between the time he turned out his reading light at night and the time he fell asleep, he would focus his mind on whatever scientific problem most puzzled him. He found that by doing this his dreams would help him work on the problem all night.
Despite everything, no answer to the 5.1-angstrom dilemma appeared. So Pauling made a fateful decision. Feeling "forced into it by the Bragg, Kendrew and Perutz paper," he resolved to ignore this essential piece of contradictory experimental evidence and publish at least a preliminary note about his models. There was no sense waiting any longer. If he was right—if there was some as-yet-to-be-discovered explanation for the discrepancy between his models and the x-ray data—he had to get into print first or risk losing his place in history. If he was wrong, it would not make any difference when he published.
On October 16, 1950, Pauling and Corey sent the Journal of the American Chemical Society (JACS) a short note to establish priority, mentioning that they had come up with two spiral models, one with 3.7 amino-acid residues per turn, the other with 5.1, with a mention of the hydrogen-bonding scheme and the assertion that strong evidence existed that the proposed structures were present in a variety of proteins. They hinted as well at their model for silk. That was all; at the end, the authors promised that "a detailed account of this work will be published soon."
Then came good news. Pauling got wind of new data from a British firm called Courtaulds, a manufacturer of artificial fibers. The company's researchers had succeeded in making wholly synthetic polypeptide chains made of only one type of amino acid. These man-made chains behaved in some ways like natural keratin but in other ways were tantalizingly different. The Courtaulds scientists found that their synthetic chains packed together like pencils in a box—to Pauling, this looked like evidence in favor of a spiral configuration, which would give an overall shape like a long, thin cylinder—and they also found that there appeared to be hydrogen bonding along the length of the chains. The best news of all, however, came from the group's most detailed x-ray pictures: The synthetic fibers gave no 5.1-angstrom reflection.
Pauling was elated. Here was a structure that appeared to be a spiral—or more precisely a "helix," a word that Pauling began using around this time after he was introduced to it by one of his postdoctoral fellows, Jack Dunitz—yet did not show evidence of that confounding repeat distance. Perhaps the 5.1-angstrom reflection in natural keratin was not as important as everyone thought. Perhaps it was an artifact or due to some higher level of structure in natural keratin and he was justified in ignoring it. With renewed vigor, Pauling and Corey continued their model building, constructing final versions of their two helixes, the tighter of which Pauling termed alpha, the looser gamma, and two versions of the extended silk-like patterns, which he and Corey now called pleated sheets.
The news circulated at Caltech that Pauling's team was constructing protein models precise to the finest detail. This especially interested the institute's biologists. When Pauling gave a seminar to them that winter on his ideas, the large lecture room in the Kerckhoff Laboratory building was packed, the audience buzzing. "Everybody knew this was going to be pretty hot stuff," biology professor Ray Owen remembered.
Pauling delivered the talk with his usual dramatic flair. He entered flanked by assistants carrying a variety of props, one of which was something tall wrapped in cloth and bound with string like a piece of statuary about to be unveiled. Everyone knew that it was "the Model." Pauling began his talk by going over the basics of protein structure, drawing diagrams to illustrate the importance of hydrogen bonding and the flat peptide bond. He held up a child's set of soft plastic pop-beads and snapped them together to show how amino acids connected. After a suitable introduction, he started moving toward the Model, taking a jackknife from his pocket and opening it, reaching for the string. The audience members leaned forward in their seats. Then Pauling, the master showman, thought of something else and backed off. Everyone sat back. Noting the effect this had, he repeated the trick several times. "He really built up a great deal of suspense," Owen said.
When he had had enough fun, Pauling unveiled it with a grand flourish: a beautiful, multicolored model of his tight spiral, the alpha helix. It was the first time many in the audience had seen a space-filling molecular model, and it had an effect. It looked "real," a knobby skein of close-packed atoms painted bright red, white, and black, twisting up and around to form a thick, knurled column. The helix's gentle curve could be traced with the eye, atom by atom; it had depth and weight and density, a kind of visual impact that no other models had ever approached. It was Pauling's intuitive structural-chemical vision made manifest. It was a sensation. Pauling ended his talk with evidence of its existence in a variety of natural substances, and afterward the Caltech professors and students crowded around, shaking his hand, asking questions, looking close, reaching out to touch the helix.
Shows like the Kerckhoff seminar were something like out-of-town previews, giving Pauling a chance to respond to any criticisms before writing more detailed papers. But there were no significant criticisms. Everyone seemed very impressed. Pauling was now feeling better about his structures, especially the alpha helix.
With growing confidence, Pauling and Corey expanded their repertoire through the winter of 1950-51, coming up with models for proteins like collagen, feather rachis, gelatin, and muscle, many of them involving the alpha helix as a component in more complex structures. Their collaboration had settled into a routine: Pauling coming up with the basic ideas for structures, Corey patiently and exactingly turning these insights into precise, finished models. They would talk over the rough spots, the places where Corey's work showed weaknesses in Pauling's vision, and together they would smooth them out. Structure after structure fell into place in this way, and rumors of success sped around the world. At the Cavendish, Bragg's people, who had paid little attention to Pauling and Corey's early, rather cryptic note in JACS, waited nervously for Pauling's more detailed papers to appear. In New York, Warren Weaver, eager for news of this string of breakthroughs, dispatched a Rockefeller Foundation officer familiar with protein work to Pauling's laboratory in February 1951. W. F. Loomis found it a place full of wild ideas. "He certainly is imaginative, daring, and brilliant," Loomis noted in his diary after spending a day with Pauling. "But he has gone off the deep end in some cases (such as the 'artificial antibody' story) and his many stimulating pictures, models, etc. may be largely figments of his own imagination rather than lasting and sound science."
A Broadside
The deep end! Pauling might well have agreed. He was taking a chance at a number of levels. The Courtaulds data might simply be a peculiarity of artificial polypeptides; the absence of a 5.1-angstrom repeat might have nothing to do with real proteins, which always seemed to offer the x-ray reflection that Pauling's models could not. He still had no good explanation for that. By deciding to move forward despite that discrepancy, he was taking a chance that Bragg's group, for example, would never take. At the Cavendish, they followed their x-ray data slavishly, letting the spots on the photographic plates determine their models. In Pasadena, however, with its inferior x-ray equipment and smaller staff of crystallographers, it was necessary to take a chance to win. It was daring to play the game at the level Pauling had chosen, to demand precision in protein models down to the tenth or hundredth of an angstrom for molecular structures hundreds of times more complex than anyon
e had ever analyzed. Anyone else would have equivocated like Bragg or waited until the data were more settled.
But there was no one like Pauling. Now middle-aged, at a time in life when many scientists were content to rest on their youthful accomplishments or try their hand at administration, Pauling found himself more energetic, more focused, and more self-confident than ever.
And self-confidence would prove the deciding factor. He had an unbounded belief in his grasp of chemistry; he understood the discipline in its entirety as well as or better than anyone else on earth. Structure was his specialty, and all of his chemical understanding told him that the alpha helix and his other protein structures had to be right. They had been built upon solid rules; months and months of careful model building had confirmed their strength. He had a choice between believing in himself—in his approach to solving large molecules, in his stochastic method of setting up rules and building models—or in believing a spot on the x-ray photos. He chose to believe in himself.
Belief was becoming a necessity for Pauling. His growing political troubles had forced him to examine the depth of his beliefs in that sphere; he had already faced the choice of following them or knuckling under to an investigatory committee. He held firm—while still finding a way to avoid a contempt citation. When pushed, he pushed back harder. He was stubborn and sure of himself. He was at the top of his game and had no intention of letting up. Not when the secret of life was within his reach.
On his fiftieth birthday, February 28, 1951, Pauling blew out the candles on the cake his staff had baked for him, accepted the good wishes of his coworkers, and mailed a manuscript to the Proceeding of the National Academy of Sciences (PNAS). "The Structure of Proteins: Two Hydrogen-Bonded Helical Configurations of the Polypeptide Chain," by Pauling, Corey, and Branson, was a complete, extremely detailed description of the structure of the alpha and gamma helixes.
In later years Branson complained that he had not received proper credit for his contributions to discovery of the alpha helix. There is a paucity of primary documents to confirm or belie his claim, but this much is known: He arrived in 1948 and spent roughly a year in Pasadena working with Pauling’s group. During that time he was asked by Pauling to determine all helical structures for protein chains that satisfied certain restrictions and requirements. Among these it is likely that Pauling insisted that all peptide bonds be planar; that bond lengths and angles conform to the precise figures Corey had obtained for amino acids and peptides; and that structures allow for as many hydrogen bonds as possible between turns of the helix. In addition, Pauling wanted to tie Branson’s work to the available x-ray data; for this purpose the visiting professor was assisted in his calculations by Sidney Weinbaum. Finally, it is likely (although documentation has not been found) that Pauling advised Branson not to be hampered by the idea that there had to be an integral number of amino acids per turn. Pauling had long known that nature, at least at the level of molecules, did not always fit itself into neat, whole numbers; that concept might have permeated his laboratory (as the lure of integral repeats permeated the Cavendish) without him having to stress it.
In late 1949 Branson presented Pauling with only two candidates, the gamma and alpha helixes. He then returned to Howard University and other work. Branson appears to have given proteins little thought until he received a note from Pauling in late 1950 along with a draft copy of a paper on the alpha and gamma helixes. “Dr. Weinbaum did a great amount of work, based on your original notes, and I think that a discussion of the configurations of the spirals is in good shape,” Pauling wrote, asking for Branson’s suggestions on the manuscript before he sent it in for publication. Branson was listed as third author.
There is no record of a reply. Branson went on to a significant career, staying on as chair of the physics department at Howard University for many years, and later serving as president of two colleges. In 1984, however, as he was nearing retirement, Branson wrote Pauling biographers Victor and Mildred Goertzel implying that his contribution had been greater than the final paper indicated. “I took my work to Pauling who told me that he thought they [the proposed alpha and gamma helices] were too tight, that he thought that a protein molecule should have a much larger radius so that water molecules could fit down inside and cause the protein to swell,” he wrote. “I went back and worked unsuccessfully to find such a structure.” When he received Pauling’s note and the draft manuscript, Branson wrote, “I interpreted this letter as establishing that the alpha and gamma in my paper were correct and that the subsequent work done was cleaning up or verifying. The differences were nil.” He added in his letter to the Goertzels that he “resented” the later attention lavished on Pauling and Corey. In an interview just before his death in 1995, Branson added that he thought Corey had nothing to do with the discovery of the helixes.
Arguments over priorities in scientific discoveries are more common than most people think. Sometimes it takes years for old resentments to surface; this seems to have been the case with Herman Branson. The issue might be resolved if Branson’s original report to Pauling was found. But because it is not available, and because of the overall paucity of the written record, it might never be possible to firmly place proper credit in the discovery of the alpha and gamma helixes.
So we are left with interpretation. It seems, in the opinion of this writer, that while the order of the authors on the resulting paper might be questioned, the names of all three men are appropriate. In light of what is known about the operation of Pauling’s laboratory and the general role played by Robert Corey, it is clear that Branson was given a specific task and carried out significant work. That work, however, was assigned by Pauling, made possible by Pauling, directed by Pauling, and, most important, guided by chemical restrictions set forth by Pauling. Without Pauling, Branson would likely have never worked on these protein structures at all. Without Pauling’s laboratory support – Weinbaum’s calculations, for instance, and the other talent available there for suggestions, review, and interpretation of his work – Branson might not have been able to accomplish his task. Without Pauling’s restrictions on possible structures – again, key to solving the problem – Branson would likely have come up with little or nothing in the way of results, just as the British had.
A final note: Branson’s comment that Corey had little to do with the final results seems off-base. Branson was in his mid-thirties, still relatively young when the work was done, and had little experience in building molecular models from x-ray data. Corey, seventeen years his senior, was unsurpassed in the world at that time in turning difficult-to-interpret x-ray patterns into solid, proven, precise molecular models. According to Branson’s much-later memory, he started building models on his own before Corey got involved, then, “One day Corey came by with some large F-H atomic models. We attached them as the alpha helix. Corey’s response on viewing the spiral was ‘Well, I’ll be damned.’” That image of a relative novice astonishing a master of the craft seems unlikely, given their relative levels of experience and the technical difficulties involved in this sort of model building. While Branson undoubtedly used his mathematical skills and knowledge of physics to narrow the possible helixes, it is difficult to imagine that Corey’s efforts would not have been central in achieving the highly accurate, very precise models that were eventually published.
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Excited and unable to hold back the good news until the paper was published, he immediately started telling others about the singularity and significance of his work. "The difference between our two predicted configurations and the others that have been described in the literature is that ours are precise, whereas the others are more or less vague," Pauling wrote Warren Weaver a few days after sending in his paper. "I feel in a sense that this represents the solution of the problem of the structure of proteins." Weaver, elated with this justification of his twenty years of support for Pauling, immediately sent the Rockefeller Foundation's resident science writer and publicist, George G
ray, to Caltech to prepare a full report for the trustees. Gray found Pauling a publicist's dream, a scientist who knew how to communicate his research in simple, colorful language. ("I try to identify myself with the atoms," Pauling told him. "I ask what I would do if I were a carbon atom or a sodium atom.") Weaver began reconsidering the desirability of a multi-million-dollar grant for chemistry and biology at Caltech. Before his paper appeared in print, Pauling also wrote Dennis Flanagan, the editor of Scientific American, that he and Corey had cracked the protein structure problem, adding, "It seems to me to be just about the most important step forward that has been made during the last 25 years or perhaps 50 years in this field." Flanagan quickly wrote back asking more about this "bombshell" and begging Pauling to write an article on protein structure for the magazine.