Force of Nature- The Life of Linus Pauling
Page 27
Corey
Through his year of waiting for the chairmanship, Pauling continued traveling, speaking, teaching, and publishing a staggering amount of work, a paper every three or four weeks: more magnetic studies of hemoglobin, more organic and inorganic molecular structures, a new theory of the color of dyes, insights into the structure of metals. His quantum-mechanics textbook with Bright Wilson reached print. He also made plans to write a book on the application of his resonance ideas to organic chemistry, and together with his former student, George Wheland, wrote several chapters (then put it aside in the press of other activities and never completed it).
His number-one goal, however, was to crack the problem of the structure of proteins. He started attacking it on several levels at once. In May 1937, Astbury visited Pasadena, talked with Pauling, and showed him some of his new x-ray photographs of keratin. Both men agreed that the molecule was a long chain but disagreed on the finer points of structure. "I knew of course what Bill Astbury at Leeds had written about the structure of keratin—hair, horn, fingernail and so on. But I knew that what Astbury had said wasn't right. . . because our studies of simple molecules had given us enough knowledge about bond lengths and bond angles and hydrogen-bond formation to show that what he said wasn't right," Pauling said. "But I didn't know what was right."
Astbury, like Bernal and the rest of the English protein x-ray crystallographers, was trying to solve the structure directly from the complicated x-ray scatterings. Pauling preferred his own stochastic approach, the method that had worked with the silicate minerals: Learn everything possible about the sizes and shapes of the component parts, make assumptions about the bonds that hold them together, use that information to build precisely crafted models, then see if the models fit the x-ray data.
He decided to try to solve keratin that way. The building blocks were amino acids, but unfortunately there were no decent x-ray analyses of the structure of these rather complex molecules. Even without good structural data, Pauling thought he knew enough about related molecules to make a stab at how amino acids could string together to create Astbury's alpha-keratin pattern. Important among Pauling's assumptions was his earlier idea that the peptide bond had to have considerable double-bond character, thus restricting rotation and holding the atoms on either side of it in the same plane. This, together with a general idea of the basic sizes of amino acids and a belief in the importance of hydrogen bonds, gave him his starting point.
He puzzled for weeks through the summer of 1937, trying to arrange amino acid chains to match Astbury's x-ray results and provide a maximal amount of hydrogen bonding. He tried to make a flat, kinked ribbon structure like Astbury's; he could not make anything of that sort fit the x-ray data. He tried some ideas that wound the chain around in three dimensions; those did not work, either. One major problem was data of Astbury's indicating that there was some sort of major structural repeat along the chain about every 5.1 angstroms. (An angstrom is one ten-millionth of a millimeter.) Nothing Pauling built matched that.
By the time September arrived, Pauling had given up. Maybe his ideas about amino-acid structures were wrong. Maybe the bond lengths and angles he was carrying over from other structural studies did not work the same way in proteins. Maybe the peptide bond was not held flat but could twist. Maybe there was something wrong with his ideas about hydrogen bonding.
The maybes could be eliminated only through the painstaking work of nailing down the precise structure of individual amino acids and confirming the way they linked together. Pauling had already started a graduate student, Gus Albrecht, growing amino-acid crystals for analysis. But he needed more talent than a graduate student alone could offer: Amino acids were bigger and more difficult than any organic molecule that had yet been subjected to x-ray analysis—even the simplest amino acid, glycine, contained ten atoms in some complicated arrangement—and success would require insight, skill, and possibly several years of grinding labor. Where would he find someone with that combination of skill and stamina?
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Fate brought Pauling the person he needed in the thin, crooked form of Robert Corey. Corey was one of the few men in the nation highly skilled in the crystallography of proteins. After getting his Ph.D. from Cornell in 1924, he had worked for years assisting Ralph Wyckoff in the x-ray analysis of everything from porcupine quills to crystalline hemoglobin at the Rockefeller Institute for Medical Research. When Wyckoff's lab was eliminated in an administrative shake-up, Corey had been sent off with a year's pay, whatever equipment he could talk Wyckoff out of, and a good recommendation. In April 1937, Pauling got a letter from Corey asking it if might be possible for him to come to Pasadena for a year if he brought his own equipment and paid his own salary. Pauling, of course, said yes but warned Corey that there was a good possibility there would not be money enough to add him permanently to the staff.
Pauling may have had second thoughts when he met Corey, who looked older than his forty years, with a lank frame, thinning hair, and small black mustache. He had been severely crippled as a child by infantile paralysis and had never fully recovered; he limped badly and used a cane. He was also shyer, a bit more retiring than Pauling liked—"a gentle and tender man," Pauling would later say. But after talking awhile, it became clear that Corey knew all about x-ray crystallography. There was something else there, too: a furtive intelligence that shone out briefly, a sense that Corey knew a good deal more about things than he might say aloud. He told Pauling that he had already started on the first stages of an attack on glycine. Pauling recalled later: "He and I together decided that he should work on the determination of the structure of some crystals of amino acids and simple peptides." Then he corrected himself. "When I say that he and I together made this decision, I may not be quite right. It is not unlikely that he had already made the decision, and that he arranged to have me agree with him, in such a way that I would think that we had made the decision together. I learned later that he was very good at this."
It was the beginning of a long and fruitful relationship.
The Infallibility of Pasadenan Research
Soon after Corey arrived, Pauling left Caltech to spend four months at Cornell University, where he had accepted an invitation to become the George Fisher Baker Lecturer. This prestigious appointment involved giving a series of talks on a single subject, which were traditionally edited into a slim book published as one of the Baker series by Cornell University Press. Pauling's chosen topic was the nature of the chemical bond. He arrived in Ithaca at the end of September with Ava Helen, leaving the children—twelve-year-old Linus junior, six-year-old Peter, five-year-old Linda, and a fourth child born just three months earlier, Edward Crellin—in the care of friends, and settled into the university's Telluride House. Ava Helen welcomed the chance to take a break from a houseful of youngsters and looked forward to the longest time she and her husband would have alone since their first trip to Europe a decade earlier. The Paulings made the most of it, attending receptions and dinner parties and making occasional forays into New York to see the latest musicals and to go dancing.
Freed from the daily chores of chairmanship at Caltech, Pauling also had plenty of time to work on a major project he had been planning for some time, a coalescence of all of his ideas on the chemical bond into one book. He would use his Baker lectures as a starting point, but the resulting book would be much more comprehensive. He worked on the manuscript through the months of their stay in Ithaca and expanded it through 1938 after returning to Caltech.
When it appeared in 1939, The Nature of the Chemical Bond and the Structure of Molecules and Crystals: An Introduction to Modern Structural Chemistry became an instant classic. It was targeted to graduate-level chemistry students for use as a text in upper-division courses, but its impact went far beyond the classroom. The book would change the way scientists around the world thought about chemistry. For the first time, the science was presented not as a collection of empirical facts tied together by practical fo
rmulae but as a field unified by an underlying physical theory: Pauling's quantum-mechanical ideas about the chemical bond. By detailing how the nature of the chemical bond determined the structure of molecules and how the structure of molecules determined their qualities, Pauling showed for the first time, as Max Perutz said, that "chemistry could be understood rather than being memorized." The book also introduced chemists to the importance of x-ray and electron diffraction as important tools for determining atomic bond lengths and angles, which in turn could disclose something about the nature of the bonds between them. Before its publication, few chemists had taken notice of the arcane art of crystallography; after its publication no chemist could ignore its value.
Notably, the book was written clearly and in a language chemists could understand. Pauling purposefully left out almost all mathematics and detailed derivations of bonding from quantum mechanics, concentrating instead on description and real-world examples. The book was filled with drawings and diagrams of molecules; it was, considering the breadth and depth of its content, amazingly readable.
The response to its publication was immediate and enthusiastic. A University of Illinois professor's letter was typical: "I cannot refrain from taking the opportunity to express to you congratulations and my personal appreciation for one of the finest contributions to chemical literature that I have ever read." G. N. Lewis, to whom Pauling had dedicated the book, wrote, "I have just returned from a short vacation for which the only books I took were half a dozen detective stories and your 'Chemical Bond.' I found yours the most exciting of the lot." Sales were strong.
The Nature of the Chemical Bond soon became a standard text at most of the nation's leading universities. It went through three editions, was translated into French, Japanese, German, Russian, and Spanish, and stayed in print for almost three decades. It became a Bible for a new generation of chemists and one of the most cited references in the history of science.
There was, in 1939, only one criticism. The book was written with such utter self-confidence that the Harvard chemist G. B. Kistiakowsky, in an otherwise positive review in the Journal of the American Chemical Society, could not refrain from noting, "Dr. Pauling has been so successful in his attack upon many of the problems in the field that his advocacy of the infallibility of Pasadenan research and the somewhat pontifical style in which this book is written are understandable and should not be taken amiss."
The reference to a pontiff caught the eye of Pauling's irrepressible hemoglobin coworker Charles Coryell, who, the next time he saw Pauling on campus, loudly called a hello to "Pope Linus the First." Pauling thought that was funny, but reminded Coryell that there had already been a pope named Linus during the first years of Christian Rome. More properly, he pointed out, he would be Pope Linus the Second.
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When he returned from Cornell in early 1938, Pauling found that Corey had, in the intervening months, made astonishing progress on the structure of amino acids. Spurred by the specter of unemployment, Corey had worked day and night on solving glycine and was already nearing his final analysis. Pleasantly surprised, Pauling agreed that he should continue his work and expand it to diketopiperazine, a compound of two glycines linked in a ring, in order to get information on the peptide bond.
Corey was vigorous, meticulous, and innovative in his use of some of the newer techniques of x-ray analysis. He quickly solved the diketopiperazine structure and followed that up in 1939 with his and Gus Albrecht's detailed description of glycine, both papers solid work and both landmarks in the development of a theory of the structure of proteins.
Corey would stay at Caltech for more than two decades, the remainder of his professional life, becoming Pauling's right hand in the x-ray laboratory. Theirs was a scientific collaboration that worked because the two partners were so different. Even-tempered thoroughness, precision, and logical analysis were Corey's strong points, and they formed a perfect complement to Pauling's flashes of theoretical insight and impulsive leaps of understanding. Corey was cautious where Pauling was bold, introspective where Pauling was outgoing, reticent where Pauling was sometimes rash. Pauling would rush ahead with the big ideas about proteins; Corey would patiently grind out the required x-ray data and rein him in until they were sure.
It was a perfect match.
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On May 16, 1938, Pauling gave his first major public address as chairman of the Caltech Division of Chemistry and Chemical Engineering. The occasion was the dedication of the new Crellin Laboratory for research in organic chemistry, three floors underground and three above, a physical link between the Caltech divisions of chemistry and biology. With Pauling as shepherd, the bio-organic grant request to the Rockefeller Foundation had gone smoothly—Caltech received a quarter of a million dollars over five years, including funds for new professors, specialized equipment for the Crellin Laboratory, and ten thousand per year for Pauling's own projects in structural chemistry—and he felt a sense of pride in making Noyes's last great project a reality. The crowd included all of Caltech's top officials as well as many of the richest and most powerful men and women in Southern California.
Pauling kept his part of the program short. A spring breeze ruffling his hair, Pauling stood on the outdoor dais and spoke of the research that would take place in the new laboratory, a place where a small group of men would explore a "field of knowledge of transcendent significance to mankind which has barely begun its development. . . . the correlation between chemical structure and physiological activity . . ." The building's donor, Edward Crellin, a retired steel magnate, then spoke in plainer terms of his expectations: ". . . the search for, if not the elixir of life, a better understanding of vital processes, leading to better health and longer and happier lives." They both received polite applause. Then Pauling endured a round of handshaking with current and potential donors before getting back to the task of moving into his new laboratories.
The Crellin Laboratory marked a new phase of life for Pauling. Its completion not only expanded his laboratory space; it confirmed his success as a leader. He would equip it with the best men and the most sophisticated equipment available—x-ray spectrophotometers, ultracentrifuges, electron-diffraction machines—and use it to push chemistry into new directions. He was so pleased with it and its benefactor that he and Ava Helen surprised everyone by naming their most recent child Edward Crellin Pauling. ("Not accepting the nurse's suggestion that he be named Caboose," Pauling noted.)
Their family life entered a new phase as well. With four children and a larger salary, the Paulings both needed and could afford a larger house. Just after the Crellin opening, they bought a large lot about five miles from campus in the hills below Mount Wilson, a beautiful, isolated two acres perched on the edge of an arroyo with a spectacular view, and began planning their dream home—a rambling California ranch-style house, two long wings joined at an angle, fronted with adobe-style brick. It would be a home designed to live in, not to impress people, with pleasant views and a big fireplace in the living room, bookcases everywhere, and plenty of room for the children to play. There would be six bedrooms (one apiece for the four children and the parents and one for the maid), a study for Pauling off the living room, and a large kitchen and garden space for Ava Helen. Pauling was active in every phase of the planning and presented his architect with some unusual requests. One was that Pauling's study should be crystalline in outline: octagonal, encased in bookshelves, with a view over the arroyo. Another was that the two wings of the house should join at an angle of precisely 109.47 degrees—the tetrahedral angle of carbon. The architect accommodated the first request but talked Pauling out of the second, which would have required some unusually difficult planning. They compromised and joined the wings at 120 degrees, the bond angle in benzene.
All of this was expensive, but Pauling could afford it. Nine thousand dollars a year was a fortune during the Depression, and after years of poverty growing up and more than a decade of grad-school and junior-faculty
penury, Pauling intended to spend his salary, and to do so with some style. As a final reward to himself for achieving the chairmanship, he bought himself a Lincoln Zephyr, a powerful, flashy car that he drove very, very fast.
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Now that the Crellin Laboratory was built, it became important to find scientists to fill it. The original intent had been to hire one world-class senior organic chemist to complement Pauling, a man around whom grants and students would coalesce, thus quickly assuring the success of the program. In addition, the Rockefeller funds provided enough money for one or two promising younger men.
The senior post was a problem. With Conant out of the picture and Pauling unimpressed with any other U.S. talent, Weaver tried to help by sending his agents to scour Europe. For a year he and Pauling courted the great Scottish organic chemist Alexander Todd, an outstanding scientist with a strong history of success and a structural viewpoint that complemented Pauling's. They paid his way to Caltech for six months in hopes that the warmth and hospitality of Southern California would work its magic. Todd, however, chose to stay in England.
Pauling then became enthusiastic about a Hungarian, Laszlo Zechmeister, whose specialty it was to purify and study organic molecules using a recently rediscovered technique called chromatography. Chromatography made it possible to separate specific biomolecules out of the complex stew in which they normally existed, cellular fluids and organic solutions. Dissolved in a proper solvent, the molecular mix was allowed to migrate across a solid such as a piece of paper or beads of purified silica. Depending on the solvent and the solid used, some molecules moved faster, some slower; eventually, purified forms could be separated completely. "Zecky," as he was called, was especially interested in carotenes, large molecules that give the yellow and red colors to such vegetables as carrots and tomatoes. The carotenes were conjugated molecules—they had alternating single and double bonds, like the pyrroles in hemoglobin—and Pauling was interested in their structure. Despite a lukewarm response from Weaver, who thought the Hungarian was too little known to attract the support others could, Pauling hired Zechmeister for the senior post. It would turn out to be a mixed blessing. Zecky would help introduce chromatography to the United States and make it an important and much-used laboratory technique. But he had little scientific ambition and would never ascend the scientific heights later scaled by Todd.