by Thomas Hager
On the train back, Pauling seemed calm, but inside he was shaken. Both his mother and father had died young. The man he was named after, grandfather Linus Darling, had died of kidney disease. Was he fated to follow him? Back in Pasadena, waiting for the recommendation of a specialist, he dealt with his depressing diagnosis the only way he knew how: He threw himself into work, finishing a major grant request for the Rockefeller Foundation and reading everything he could about kidney disease. One fact stood out among the many he learned: most experts agreed that there was no effective treatment for Bright's disease.
Pauling's mood darkened, but he kept it inside and kept working. Aside from being more easily tired and twenty pounds heavier than normal, he did not feel ill. But he worked in bed, as the doctors had advised, for two weeks, until arrangements were completed for him to see the West Coast's leading kidney specialist. The name they gave him was Thomas Addis, head of the Clinic for Renal Diseases at Stanford University.
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Pauling needed hope, and Addis provided it. He was a tall, handsome, charismatic Scot who looked younger than his sixty years, with a gentle, somewhat absentminded but reassuring manner and a vast background in the classification and treatment of Bright's disease. Addis's twenty years of study had convinced him that Bright's was not one disease but several, with different pathologies. His approach to diagnosis was suitably scientific in Pauling's eyes: He made a quantitative measurement of urinary sediment over time (the Addis count), which told him something about the nature of the kidney problem, and also the urinary urea clearance (the Addis urea ratio), which indicated the extent of the damage. Addis was one of the few physicians in the world who believed that Bright's could be treated. He had a theory about it, based on the idea that the disease depended on a balance of tissue destruction and restoration. The trick was letting the kidneys rest. The kidneys' major work, Addis told Pauling, consisted of concentrating urea for elimination from the body. Urea was produced from protein metabolism. In order to heal, Pauling's kidneys needed to process less urea. The most straightforward way to do this was to cut down on protein intake.
Pauling had read enough by now to know that Addis's ideas were considered controversial by other kidney experts, who pointed out that protein was also required to rebuild damaged kidney tissue. On the other hand, the other experts also routinely gave up on Bright's patients. Addis at least attempted a cure.
For days, Addis tracked Pauling's urine output, sediment amounts, and urea clearance, sometimes bringing Pauling into his laboratory to watch the tests being analyzed firsthand. Every day, he came to talk with his star patient—they occasionally shared teatime together, a routine Addis observed religiously—and the two men found that they had much in common. Pauling was impressed with Addis's approach to the disease and his belief in scientific measurement as a basis for diagnosis. They talked about kidney function and hemoglobin metabolism and about politics: Addis, one of the Bay Area's most outspoken antifascists, a supporter of civil rights and a believer in Soviet Russia, ran his clinic along socialist lines.
After two weeks together at Addis's clinic, they became good friends. Then, one day, Addis walked in and told Pauling that he should go home. His tests had shown that Pauling's condition could be treated with an extremely low protein, salt-free diet, which would lower the production of urea and reduce the swelling in his tissues. Ava Helen would make sure he stayed on it; Addis had already given her some ideas for menus. He could keep track of Pauling's progress from Stanford by looking at his urine analyses every week. Just stay in bed and eat properly, he told Pauling; don't work too much and give your kidneys a chance to heal.
This sounded reasonable. Back in Pasadena, Pauling was installed in a bed in the study of his house and put on Addis's diet, with its emphasis on fruits, grains, and vegetables, along with supplemental vitamins and minerals and lots of water. He cut his correspondence to a minimum, delegated most administrative duties to Sturdivant, and tried to stop thinking about science by immersing himself in mystery novels. Ava Helen became his nurse and dietitian, carefully preparing his food, weighing each portion to the fraction of an ounce on a newly purchased postage scale, figuring total protein and salt, and noting everything in a spiral notebook. Making saltless, meatless meals interesting became her personal challenge. She found ways around the usual bananas and gelatin, supplementing the bland fare with occasional treats like escargot captured from her garden, fed for days on cornmeal and steamed in the shell. Snails, she explained to Pauling, were very low protein.
The Addis regimen seemed to work. Pauling forced himself to stay in bed, first all day, then later for half days. After four months the edema was gone; after six Pauling found his mental energy and good humor returning to normal. He corresponded often with Addis, visited him occasionally, and became an enthusiast for his methods. He later nominated Addis for the National Academy of Sciences, ensured his election, and helped him get government funding for kidney studies during the war. He stayed on his low-protein diet for almost fifteen years and attributed his survival and good health to Addis's ideas. Addis, for his part, told Pauling that Ava Helen deserved credit, too: Very few other patients were able to stay on his diet so religiously for so long.
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To those who worked with Pauling, the cure seemed a miracle. There had been some serious talk about what the division would do without him. Now, within a year, he was back and seemingly better than ever. "We thought we might lose him," Eddie Hughes remembered. "And for many years after that, it seemed to me that he was getting younger every year instead of older."
By September 1941 he felt well enough to go to the University of Chicago's fiftieth anniversary celebration, a great affair highlighted by the awarding of fifty honorary doctorates in fifty fields of learning. Pauling was pleased to receive the honor in chemistry. He began to throw himself into projects again, including his antibody work and the transformation of his lecture notes from freshman chemistry into a textbook.
But the book project was put aside, along with many others, when the news came that the Japanese had attacked Pearl Harbor.
Bombs and Rockets
America's formal entry into the war on December 7, 1941, merely confirmed what the Caltech community already knew was going to happen. Within days of the attack, Robert Millikan, now seventy-three years old, appointed a committee to ensure the institute's security. Japanese sabotage and bombing attacks were the major worry, and the committee went a bit overboard in the frenzy following Pearl Harbor. During a comic-opera period of a few weeks early in the war, squads of Caltech students, armed with ax handles, were put on patrol around important buildings. The suggestion was made to Pauling that an armed guard be placed outside every laboratory in Gates and Crellin, but he assured the administration that a single watchman making tours of inspection through the night would be enough. Caltech's researchers turned their thoughts from the structure of the universe to the design of homemade gas masks and methods of keeping glass from shattering during bombing raids, and Pauling, along with every other scientist working on military contracts, was fingerprinted and given a security check.
Far more important than the surface changes on campus was the flood of money the war would bring to Caltech. In Washington, D.C., Caltech's Charlie Lauritsen became an enthusiast for the military use of rockets and convinced the military that Caltech could become a national center in that area despite its limited prewar experience with rocket research. Three months before the Japanese attacked Pearl Harbor, the first $200,000 in federal money for rocket research was sent to Pasadena—an amount equal to about one-sixth of the institute's total prewar annual budget. Lauritsen set up a rocket-propellant plant in the foothills near Pasadena and ran it around the clock under the direction of one of Pauling's faculty members, the chemical engineer Bruce Sage. "Very few people realized we had enough high explosives up there to have blown Pasadena off the map," one participant remembered. By 1944 funding for the rocket program alo
ne would grow to $2 million per month, employing thousands of workers, contracting with hundreds of businesses, and creating an entire new industry in Southern California. As Lauritsen's right-hand man on the project put it, "A large part of Caltech literally had become a branch of the Bureau of Ordnance."
The major problem with rockets was that they were undependable. Lauritsen stood at navy firing ranges and watched rocket after rocket blow up prematurely or veer off course. This, he believed, was because of the propellant being used, an American-made powder that burned erratically, far inferior to those he saw being used in England. With better propellants and more scientific design, Lauritsen believed, rockets could be made more accurate, more trustworthy, an important part of the war effort.
Pauling, too, became interested in propellants and explosives. After war was declared, he offered his expertise to the government in the area of powder research. He was made a member of the explosives division of the NDRC—now a subsidiary, along with the new Committee on Medical Research, of the OSRD—and chair of a special committee on internal ballistics for the rocket program. He traveled almost every month to Washington, D.C., to plan research and discuss objectives with the men running the war machine. Government funding began flowing to his lab as well, mostly for research into the analysis of powders and the development of more stable propellants. Pauling quickly became an expert, reading widely and spending some weeks in the spring and summer of 1942 visiting gunpowder and explosives factories in the East. The navy began sending a steady stream of captured German and Japanese fuels to Pasadena so that the Caltech scientists could analyze them. Under Pauling's supervision, new chromatographic techniques were developed that allowed the quick and accurate determination of the compounds in Axis rockets—even if it was just a few pinches scraped from a fragment. The expansion of Zechmeister's separation techniques to compounds such as those in explosives helped establish chromatography as an important tool for chemists. "We sort of revolutionized modern chemistry by introducing chromatographic analysis," Pauling said.
By the spring of 1942, Pauling, now healthy and eager to contribute to the war effort, threw himself into defense research. He invented an improved stabilizer for rocket powders, a composite grain that allowed the powder to burn more consistently and give a better trajectory. Some wag nicknamed it "Linusite," and it became widely used during the war. Pauling began working on a synthetic substitute for much-needed quartz crystals used in military sighting devices and codeveloped an armor-piercing shell that was later patented.
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Whenever she could, Ava Helen still kept Pauling in bed for half a day, but it was impossible to slow him down much. His naturally restless imagination now had a thousand problems to work on, and each one he chose was funded by seemingly endless federal dollars. He was like a little boy in a toy store, a blank check in his pocket. "The laboratory here has lost its leisurely air now," Pauling wrote in June 1942. "We have got so many contracts for war work that everybody is kept on the go." He toured arsenals and gave advice on the production of explosives. He analyzed chemical systems for making oxygen. He oversaw a project on aerosols. He worked on a machine for determining the molecular weights of molecules in solution and in his spare time devised what he felt was an unbreakable code (which he sent to the War Department and never heard about again). Once a month he would commute to Washington, hopping on the Super Chief for the three-day train trip east, spending a day or two in meetings, then returning. He enjoyed the trip, with its days of quiet thinking time as he stared out the window at the mountains and plains, and the feeling of contributing to the war effort.
As money flowed from Washington, the size of his laboratory grew. The powder project alone soon numbered about fifty young chemists packed into every available laboratory space and office, working as a team under the direction of Robert Corey. Corey was proving indispensable. The shy man who once preferred working with only one or two helpers bloomed during the war years into an efficient manager, devising a reporting and scheduling system that made the Caltech operation a model for other war labs.
Early in 1943, Pauling's old friend J. Robert Oppenheimer stopped by Caltech to offer Pauling a more significant chance to contribute to the war effort. They had not spoken more than a few words in the fifteen years since Oppy had tried to talk Ava Helen into a Mexican "vacation"; but Pauling had followed the physicist's career at Berkeley and knew through the grapevine that he was involved in a top-secret weapons project. Oppenheimer, still gaunt and angular, still chain-smoking and still full of himself, explained that he was in charge of a team that was trying to build a bomb based on the nuclear fission of an isotope of uranium. They were in a race with the Germans, he said, who had Heisenberg working on it, so there was probably not much standing in the Nazis' way, at least theoretically. But it had gone beyond theory here. In Chicago, a month or so earlier, Fermi and Szilard had created a controlled fission chain reaction. It seemed certain now that a fission bomb could be made that would loose the tremendous energies holding together the nuclei of atoms.
The government was putting millions and millions of dollars into the development of such a bomb, Oppenheimer explained. This was going to be a very big project, involving hundreds of scientists, all working together under strict security at a converted boys' school on a mesa top in New Mexico, a place called Los Alamos. While most of the work would be done by physicists, there would be a fair amount of chemistry involved. He asked if Pauling might be interested in directing the chemistry division of the project. A side benefit, he said, would be the availability of hard-to-get radioactive tracers like tritium that Pauling could use in his chemical biology work.
Pauling did not need long to think about it. The idea of playing underling to a bunch of physicists—especially working directly under Oppenheimer—was distasteful. The thought of bringing his wife and family to a top-secret scientific boot camp in the New Mexico desert was unappealing. He turned down the offer. "Not because I felt that it was wrong to work on the development of nuclear weapons," Pauling said, "rather that I had other jobs that I was doing."
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Pauling had many other things to think about. Early in the war he became a member of the Western Committee of the OSRD's Committee on Medical Research, where he became privy to the military's most pressing medical needs. He learned that hundreds of wounded soldiers were dying needlessly from shock, deaths that could be prevented if only they had been given plasma. But there was not enough plasma to go around. The CMR started a crash program to develop a cheap, reliable synthetic plasma substitute, and based on his experience with hemoglobin and antibodies, Pauling won a contract for its development. He gathered a team, including Thomas Addis, who would test the artificial plasmas for clearance by the kidneys, and his immunology expert Dan Campbell. Together they explored a number of chemical approaches to making something that would fool the body. Nothing worked until Pauling came up with a way to chemically alter gelatin so that it not only mimicked the gross attributes of plasma—its density and viscosity—but could be inexpensively made and easily stored. He called his preparation oxypolygelatin. Early tests on volunteers were successful, and Pauling patented the formula, giving the government a royalty-free license to use it. He also made sure the discovery was well covered by the media, announcing his success publicly and keeping clips of the wire story that went out across the nation. It came as a great disappointment when the government refused to approve oxypolygelatin because of the wide range of sizes found in the molecules in the preparation. Then, in 1943, the entire plasma substitute program was shut down because so many volunteers had come forward to donate the real thing.
"For the first time in medical history …"
By 1943, Pauling's Division of Chemistry and Chemical Engineering had been transformed: Tolman off to Washington, Niemann working on chemical warfare, faculty members Buchman and Koepfli trying to synthesize antimalarial drugs, Lucas working on plastics, Lacey on the rocket project. T
he students were almost all gone to war, replaced by military men taking specialized courses in explosives or rocketry. "Things are indeed much changed here," Pauling wrote a friend in the summer of 1943. "We have been trying to keep seminars going, but it has been hard to find material that can be talked about." Too much of the research was classified.
At the Rockefeller Foundation, Warren Weaver and his officers watched with some unease as the grant money they had awarded Pauling began to flow to war research. The great protein question that had spurred the most recent large foundation grants had been put aside as Corey and Hughes turned their attention to bombs and rockets. The development of the organic chemistry section was for the most part put on hold, too.
Only Pauling's work in immunology continued unchanged. Because it had arguably a more direct bearing on the war effort, he was able to carry through his basic research with the blessing of the powers in Washington. And Pauling's personal interest in the field was becoming intense. He even started dabbling in experimental work again for the first time in years, with Campbell teaching him how to inoculate rabbits and set up antibody-precipitation reactions. There were as yet no animal research facilities at Caltech, so Pauling built hutches for fifty rabbits near his garage at his home, assigning Linus junior and Peter to feed the animals and clean the cages. In the mornings before going off to work he would inject the animals with antigens and occasionally bleed them himself to collect the antibodies.
"I am happy to report that our immunochemical work is going extremely well," Pauling wrote Weaver in late 1941. One of his immediate goals was to prove that each antibody molecule had two binding sites, as he had proposed in his 1940 paper on antibody formation, and he devised an ingenious way of doing it. Landsteiner had perfected the technique of making synthetic antigens by attaching a chosen organic molecule to a protein; by doing this, antibodies could be raised to known structures and studied. Pauling had his workers make a series of these synthetic antigens with one, two, or three of the same organic molecules on each protein. By reacting the antibodies raised against the organic molecules with his various preparations and then analyzing the ratios of antigen to antibody in the resulting complexes, he was able to estimate how many antigens were attached to each antibody molecule. His results provided strong evidence that antibodies are bivalent, attaching to two antigens at a time. He also found what appeared to be evidence that each of the two ends of the antibody molecule could bind to different antigens, again supporting the template theory of antibody formation.
