by Thomas Hager
Pauling was behaving as he thought a father should: working hard to provide a decent home and a few luxuries for his family and disciplining the children when necessary. Although all of his children labored to earn his love, they were children, after all. He had little patience and could be short-tempered with them if they were too rambunctious or disrespectful.
His first love was science, his second Ava Helen. His children were no match.
CHAPTER 12
The Grand Plan
The Molecular Safari
Pauling was early into the war and would be early out. As soon as he read about the surrender of the German Sixth Army at Stalingrad in mid-1943, he became convinced that the Allies were going to win. At the time, he was considering the renewal of yet another wartime federal contract, this one for the chemical analysis of systems designed to produce oxygen on demand. "And then a funny thing happened in July of '43," Eddie Hughes, who was assisting him on the project, remembered. "Pauling and I knew very well that the basic work that we were doing would never get to the battlefront for two years. And for some reason or other, we decided the war was going to be over in two years, and we refused to renew the contract. We thought it would just be a waste of taxpayers' money."
By that time, a year before D-Day, Pauling was already thinking about postwar projects. He began to piece together a research idea grander than anything he had done before.
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The war made even the most enormous scientific plans seem feasible. The government was spending astounding sums of money on weapons research at university centers. More than $40 million was funneled into Caltech during the four years of the war, a sum that placed the school second only to MIT in wartime federal grants to institutions. By the end of the war, there were ten times as many people on the Caltech payroll as at the start. At MIT, the legendary Radiation Laboratory, or "Rad Lab" as it became known, grew from fifteen researchers at the beginning of the war to more than four thousand by the end, turning out a much-needed new device called radar under the direction of the young physicist-administrator Lee DuBridge. The largest single wartime project, however, was Oppenheimer's secret effort to create a new kind of bomb. By the end of the war, more than $2 billion would be invested in the undertaking, making it the single most expensive scientific project in human history.
Important for the development of postwar science, both the Rad Lab and the Manhattan Project were capped with dramatic success. They and a host of other scientific projects (including the rocket work at Caltech, which became the Jet Propulsion Laboratory) proved to political leaders that big-money, large-staff research projects—an approach that would come to be called "big science"—not only worked but worked brilliantly.
Pauling was by nature disinclined toward big science—he preferred thinking alone and handing out experiments to a few handpicked assistants—but he had been pleasantly surprised by the success of Corey's crackerjack Caltech team of fifty young powder chemists, and he thought it would be a shame to break them up when his wartime funding ended. Powder analysis would certainly not be a priority during peacetime. But there was another problem that could use a large analytic team.
In late 1943, Pauling began dropping hints with Rockefeller Foundation officials about the value of a large-scale attack on the structure of proteins. The problem was as important now as it was when Weaver had pushed Pauling toward it ten years earlier; it had merely been put on hiatus because of the war. Now, with a well-organized analytic team in place, Pauling had the perfect opportunity to revisit it with some real chance of success.
When the foundation's Frank Blair Hanson visited Caltech in January 1944, Pauling pressed the plan. Hanson, the man who had cut Pauling's artificial antibody funding, put him off, telling him that the foundation would be very interested in examining it at the appropriate time—after the war had been won. Undeterred, Pauling kept lobbying, writing Hanson that summer, "Although proteins are so complex that we can not hope that a final and complete solution of the problem of their structure will ever be obtained, we can, I think, look forward to getting in our lifetime, a reasonably good insight into the general principles of protein structure." In August, as part of a general institutional effort to organize Caltech's future research priorities, he wrote a ten-page plan for Caltech's chemistry division. Only one new research area was slated for major expansion: "the analysis and explanation of physiological processes in terms of the nature and structure of the chemical substances which are involved in them." He proposed a new program, to be placed under his direction, that would not only coordinate the work of current chemists and biologists but also bring experts in physiology, bacteriology, pharmacology, enzyme chemistry, and virology to Caltech, all working on a coordinated project that would interpret life in terms of the interplay of large molecules. This was big science indeed.
In September, Weaver was back in charge of the natural sciences division, and Pauling wrote him about his ideas. Because of the excruciating slowness of x-ray crystallography calculations, he wrote, it had taken Corey and an assistant more than a year to work out the structure of a single amino acid. But with a bigger team working with the latest equipment—including the new punch-card IBM computing machines that Pauling's team was among the first to use to crunch the considerable numbers generated during the crystal analysis of large molecules—he estimated that what Corey had done in six years could now be done in one. Pauling proposed switching twenty of his powder men to a "vigorous attack" on the problem of protein structure at the end of the war. The cost, he said, with equipment and supplies, would be about $150,000 for three years' work. Would Weaver suggest making a grant request now so that the money would be available immediately at the war's end?
Despite the price tag, Weaver was intrigued. This was a grand plan, a big-science approach to cracking protein structures. As Pauling well knew, Weaver was still chasing the secret of life, and he had vision enough to appreciate the idea of a full-scale assault on a problem that seemed to require nothing less. There was a problem, however. Despite Pauling's theoretical successes and Corey's work with amino acids, Caltech was still not known as a laboratory-based protein research center. In America, the Rockefeller Institute, the home of Bergmann and Mirsky and a dozen others, was still the number-one site for basic research in that field. There was also the memory of artificial antibodies, which left Weaver slightly more hesitant about Pauling's plans.
He responded in standard Rockefeller Foundation style, writing Pauling a lukewarm letter emphasizing the foundation's continued belief in modest scientific projects done by small groups and asking Pauling to consider less costly, more flexible approaches to the problem. Then he had an officer make a few confidential phone calls to the nation's leading protein experts, asking for their frank opinion about Pauling's grand plan. The responses were encouraging, even enthusiastic. MIT's resident protein expert, Francis O. Schmitt, reported that he had discussed Pauling's plan with a group of colleagues over lunch, and they started informally ranking the world's top protein research centers to help them make a decision. Over the next few days it grew into a full-scale analysis, with rankings for a dozen schools determined by their competence with nineteen different protein-related laboratory methods ranging from chromatography to ultracentrifugation. After running a statistical analysis of the results, they sent Weaver the rankings: The Rockefeller Institute was first; the Swedish group at Stockholm, second; Harvard, third; then the British group at Cambridge. Caltech was dead last. Not only did it have relatively few scientists involved in protein research, but its research seemed skewed toward diffraction work and immunochemistry at the expense of other likely techniques.
Despite Caltech's dismal rankings, however, Schmitt endorsed Pauling's plan. "[F]ar more important than the methods used and facilities available are the men doing the work," he wrote the foundation. "I would trade all the staff at the laboratories immediately above C.I.T. . . . for one Pauling."
Weaver began to warm to
Pauling's plan. But there was still the war to be won. He and Pauling informally agreed to hold off on more detailed discussions until after the defeat of Germany and Japan.
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On the morning of Tuesday, August 7, 1945, Pauling walked into a drugstore a few blocks from Caltech and saw the headline in the Pasadena paper: "Tokyo Admits Atomic Havoc." He bought a copy, walked outside, shook it open, and began to read, oblivious to the foot traffic and noise around him. The front page was dominated by news of the destruction of the entire city of Hiroshima in a single explosion, the enormous fireball, with the death and injury of tens of thousands of civilians. Pauling was stunned. He would remember that morning clearly for the rest of his life.
The project that Oppenheimer had tried to talk to him into joining had been a success.
Three days after the Hiroshima bomb was dropped, another atomic bomb destroyed Nagasaki. A few days after that came news of the Japanese surrender. The war was over. In the euphoria that followed, Pauling did not think much about the atomic bomb other than to wonder about how it worked. His focus was on a more immediate concern.
A week after V-J Day, Pauling appeared in Weaver's New York office to pitch an even bigger version of his ambitious plan for protein research. If proper equipment and expertise in protein techniques were lacking at Caltech, well, that could be fixed. He was talking now about the construction of two new buildings equipped with the newest and most expensive instruments—pH meters, ultracentrifuges, electron microscopes, and electrophoresis machines—and staffed with people to do virology, pharmacology, and enzymology as well as basic structural research. Only an all-out, simultaneous effort on a number of fronts would solve the protein problem, Pauling said, and Caltech was the place to do it. Weaver got caught up in Pauling's sales pitch. He could see Pauling’s vision, a cross-disciplinary effort drawing together researchers in chemistry, biology and medical research, creating something that had never existed before: "In effect," Weaver noted, "an institute of molecular biology." Despite the enormous budget numbers now being tossed around—$2 million for buildings; perhaps $6 million to support the whole project for fifteen years—Weaver began taking a "deepening and broadening interest" in Pauling's plan.
Money was not the only problem. Pauling was basing his plan on a close relationship between the Caltech divisions of chemistry and biology, and the biology division was not in good shape. After the retirement of Thomas Hunt Morgan, leadership had gone to his longtime second in command, Alfred Sturtevant, a fine scientist but someone with little capacity for administration and a limited ability to deal with people. As Pauling put it, "I think he was more interested in fruit flies than in the other members of the division." As a result, in the years following Morgan's departure, the biology division had lost both its esprit de corps and a number of its best young researchers.
After his meeting with Weaver, it became clear to Pauling that the success of his grand plan depended on shoring up the biology division. He made that a pet project.
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For two years, between mid-1944 and mid-1946, Pauling held a position of unusual influence at Caltech. Millikan, now in his late seventies, had become something of a scientific relic, a living reminder of a prewar age when scientific institutes were intimate places populated by a certain class of person. The war had changed all that, and Millikan had failed to adapt. As the conflict wound down, he began to sound increasingly irrelevant, calling efforts to increase government support of science "movements toward collectivism" and wondering aloud whether hiring Robert Oppenheimer might not add one Jew too many to the faculty. In response, Jim Page, Caltech's efficient and savvy chairman of the board of trustees, led a palace coup in 1944 that eased the Chief out of most decision making. Millikan was finally convinced to step down in the summer of 1945.
Another year would pass before a new leader of the institute was found and approved. In the meantime, Caltech was run by Page and a newly expanded executive committee of faculty and trustees. Tolman would probably have been the chemistry division's representative, but he enjoyed being a Washington, D.C., insider and one of Vannevar Bush's top advisers; he stayed in the East until 1947. That meant that Pauling was named one of five faculty members on the expanded committee, and he quickly became one of the most influential. His wartime service had been impeccable. Without Millikan around to remind people of the unpleasantness surrounding Noyes’ death ten years earlier, Pauling’s internal stature increased. His scientific reputation had never been better. Few people knew of the artificial-antibody mess, while many around Caltech were aware of his advances with rocket propellants and powders and his fruitful relationship with the Rockefeller Foundation. Under his leadership the chemistry division had come through the war with plentiful funds, a fast-growing staff, and high morale. Biology, by comparison, did not even merit a representative on the executive committee. Taking advantage of the discrepancy in power, Pauling set out to pick his own man to head biology, someone who could understand his grand plan and help make it a reality.
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There was no one in the nation better suited for the job than George Beadle. Pauling had gotten to know him in the 1930s, when Beadle was one of a talented group of young geneticists clustered around Morgan. The two men liked each other.
In some important ways, Beadle and Pauling were alike: friendly, hardworking small-town boys from the West—Beadle from Wahoo, Nebraska, where he had picked up the nickname "Beets"—both favored grantees of the Rockefeller Foundation, and both believers in the same reductionist approach to biology, a way of seeing living processes in terms of biochemical reactions that science historian Lily Kay would later call the "molecular vision of life."
After five years with Morgan, Beadle had left Caltech to take genetics to the next stage of development. While Morgan had successfully used his fruit flies to pinpoint the chromosomal location of genes, Beadle wanted to know how genes worked, the biochemical pathways that connected a site on a chromosome with the color of an eye or the shape of a leaf. When he started, it was not known exactly what a "gene" was or what it did. Did a single gene, for instance, control an entire sequence of biochemical steps leading to an expressed characteristic or only a single step in that sequence? During the war Beadle, now at Stanford, and his colleague Edward Tatum used mutants of a common bread mold called Neurospora to find the answer. Their classic experiments showed that each gene appeared to control a single biochemical reaction, which was in turn regulated by a single enzyme. The powerfully simple concept of "one gene, one enzyme" put Beadle at the forefront of American genetics. And he was more than a good lab man. Like Pauling, he knew how to make his work appealing to funding agencies. During the war he promoted his mutant molds as biological probes for use in nutrition and agricultural studies, a politically savvy move that kept him supplied with enough Rockefeller and government money to increase the size of his operation, including luring to Stanford two of Caltech's best remaining geneticists. In 1944 he was elected to the National Academy of Sciences (NAS).
Beadle knew how to run a department, how to do top-level research, and how to get money. But more important to Pauling was his approach to biology. Beadle believed that genetics was inseparable from chemistry—more precisely, biochemistry. They were, he said, "two doors leading to the same room."
Waiting in that room was Linus Pauling. At Pauling's urging, in the spring of 1945 Caltech biology head Sturtevant offered Beadle (a long-time friend) a Caltech faculty job; when Beadle turned it down, Pauling mentioned to Sturtevant that one option might be stepping down so that Beadle could be offered the biology chairmanship. Sturtevant, perhaps realizing that his heart was not in administration—or that he was not up to the sorts of plans Pauling had in mind—agreed. When Beets still balked, Pauling took the train to Stanford to have a friendly talk with him. "Don't let Pauling talk you into anything you don't want to do!" Sturtevant wrote Beadle. "What this means is that I'm a little afraid he may use unfair pressure on yo
u."
Pauling would use, of course, whatever it took. He and Beadle spoke the same straightforward language, and neither one believed in wasting time. They sat in Beadle's Stanford office, and Pauling told him, in detail, about the grand plan. Pauling was now using the term "chemical biology" to describe the proposal, and he marshaled all his persuasive abilities to convince Beadle that the two of them, working together at Caltech as leaders of a successful chemistry group and a reenergized biology division, could accomplish what no other research group in the world could: mount a successful coordinated attack on the secret of life itself. Pauling described what he saw as the whole sweep of biological research in the postwar era, a time when biology would be refashioned from the bottom up, revolutionized by a firm grounding in chemistry and an understanding of the molecular structure of the giant molecules, the enzymes and genes that together constituted life. This was the chance to find out how things really worked at the molecular level. And, he added, the Rockefeller people are very interested in this kind of project. With someone of Beadle's stature leading biology, there would be a reasonable chance at obtaining support on a scale unlike anything seen before. Pauling mentioned some numbers.
Two weeks later, Beadle accepted the chairmanship of the Caltech biology division.
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A month after that, in December 1945, a twenty-five-page grant request landed on Warren Weaver's desk. Signed by both Beadle and Pauling (but written almost entirely by Pauling), it was a clarion call for a new era in science, an outline of a coordinated molecular attack "on the great problems of biology during the coming two decades." In drafting the plan, Pauling used the sort of picturesque imagery that Weaver often employed to sell ideas to his board. He wrote of "the dark forest of the unknown" that lay below the resolving powers of the electron microscope and above the limits faced by crystallographers. It was here that proteins lay, in a molecular terra incognita to be explored by Pauling and Beadle at the head of "a great expedition armed with X-rays and similar tools. . . . The answers to many of the basic problems of biology—the nature of the process of growth, the mechanism of duplication of giant molecules, genes and cells, the basis for the highly specific interactions of these structural constituents, the mode of action of enzymes, the mechanism of physiological activity of drugs, hormones, vitamins, and other chemical substances, the structure and action of nerve and brain tissue—the answers to all of these problems are hiding in the remaining region of the dimensional forest.. . and it is only by penetrating into this region that we can hope to track them down." The molecular safari would consist of chemists, physicists, and a new breed of molecular biologist to be trained at Caltech, scientists who would think naturally of the life sciences as an extension of chemistry and physics. The expedition would be equipped with all the latest instruments and techniques that were helping to turn biology into a quantitative science: ultracentrifuges, chromatographs, spectrographs, electron microscopes, radioactive tracers, "complex and very expensive apparatus," Pauling wrote, "the best. . . that can be made. . . . No one method is good enough to solve the problem, and every method must be applied as effectively as possible."
