by Thomas Hager
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Within this astonishing output, one set of papers stood out. Pauling’s sickle-cell group had found an answer.
It had not been easy. Pauling's idea that a change in the sickle-cell hemoglobin caused it to crystallize when oxygen was removed implied a structural alteration. But for months Harvey Itano, the young physician-turned-chemist Pauling had put to work on the problem in the fall of 1946, could not find any basic difference between the blood protein from normal and sickle-cell patients. According to his tests, the hemoglobin molecules from normal and sickle-cell blood were the same size, the same molecular weight, and gave the same acid-base titration curves. His work was slowed by the fact that sickle-cell blood was hard to come by. All sickle-cell sufferers were African American, and most were from the American South; there seemed to be relatively few cases in California. Pauling and Itano first tried striking bargains with physicians in the Los Angeles black community for a small supply; for a while they lured patients to Caltech to give blood for a small sum. Eventually, Pauling found a doctor at Tulane University in Louisiana who had access to a larger supply of blood and could send what was needed.
Once they had an adequate supply, Pauling had Itano look at the effects of various chemicals on the sickle-cell hemoglobin. Itano's research confirmed that oxygen was involved in the sickling process and showed that a range of reducing agents could speed the sickling—a finding that led to a rapid diagnostic test for sickle-cell disease and the first paper that Pauling and Itano published on the subject. He also confirmed that the addition of carbon monoxide, which binds irreversibly to hemoglobin (thus blocking the attachment of oxygen), prevented sickling. As Pauling thought, the effect seemed to be localized on the hemoglobin molecule.
So why did normal and sickle-cell hemoglobin look so similar? The only detectable difference between the two was a very slight difference in the electrical charges on the molecules. Itano broke apart the hemoglobins and showed that this difference was localized in the protein part of the molecule, the globin, rather than in the iron-containing heme. But it was a very slight effect in a very large molecule. It would need an extremely sensitive probe to study any further.
To help speed the work, in the fall of 1947, Pauling started another postdoctoral fellow, Jon Singer, on the project. Singer was more experienced than Itano in the physical chemistry of large molecules, and he knew something about a new machine called the Tiselius Apparatus that might help them. The Swedish chemist Arne Tiselius had invented it just before the war to separate proteins out of mixtures based on the electrical properties of the molecules. Knowing that each protein carries a characteristic set of electrical charges on its surface, Tiselius devised a tool in which a protein solution in the middle of a glass tube was subjected to an electrical gradient, positive charge at one end, negative at the other. The proteins, he discovered, would move one way or another, drawn toward the positive or negative poles, at different speeds, depending on a variety of factors, but especially the mix of charges on their surfaces. It was a delicate, gentle, precise way to separate protein mixtures without harming them. During the war the Tiselius machines were rare and not commercially available, but Pauling put Sturdivant to work building one for Caltech.
By the time Pauling was in England, it was up and running, and Singer and Itano were able to try it on sickle-cell and normal hemoglobins. The Tiselius Apparatus finally uncovered a difference. The sickle-cell hemoglobin moved toward the negative end of the electric field more rapidly than its normal counterpart; it looked as though at normal pH the sickle-cell molecule carried about three extra positive charges. The results showed unequivocally that the hemoglobin molecules from sickle-cell patients differed significantly from those in normal people. Pauling's idea was right.
It was also surprising. The difference between a healthy human and one with a deadly disease was an almost undetectable change in the electrical charge of a single type of molecule. Pauling made sure that the singularity was emphasized in the title of the first major paper to emerge from the work: "Sickle Cell Anemia, a Molecular Disease," which came out in the fall of 1949. People had theorized in broad terms about the molecular basis of disease before, but no one had ever demonstrated it the way Pauling's group did. Singer and Itano then went further. There were patients with an intermediate stage of the disease called "sicklemia," not as severe as full-blown sickle-cell anemia; Itano and Singer showed that the blood of these patients contained a mixture of normal and sickle-cell hemoglobins. An analysis of the familial relationship between normal, sicklemic, and sickle-cell patients indicated that the trait was inherited in Mendelian fashion, with the sickle-cell gene composed of two alleles, that is, two variants, one from each parent. Sicklemic patients carried one allele, or variant, for the disease and one normal allele, with full-blown cases of sickle-cell anemia carrying both alleles for the disease.
By pinpointing the source of a disease in the alteration of a specific molecule and firmly linking it to genetics, Pauling's group created a landmark in the history of both medicine and molecular biology. It validated Pauling's belief in the importance of that dark area of the dimensional unknown where proteins lay; it turned the interest of a generation of physician-researchers toward disease at the molecular level; it substantiated his idea that medical research needed to be grounded in the methods of modern chemistry; it opened up new vistas in the study of inherited medical disorders; it kicked off years of productive research into abnormal hemoglobins; and—once again—it raised Pauling's stature, especially in the medical community.
CHAPTER 15
Attack of the Primitives
The Dream Boys
When Pauling returned to the United States, he started paying as much attention to politics as he did to science. In the summer of 1948 the nation was gearing up for one of the most raucous and surprising presidential elections in its history, and Pauling, like many New Deal Democrats, was ready to bolt the party. He felt that Truman, by moving to the right, had sold out the ideals of Franklin Roosevelt.
Pauling's candidate was Henry Wallace, Roosevelt's former secretary of agriculture and vice president from 1940 until 1944. An aloof, intelligent, well-to-do publisher of farm journals and breeder of hybrid corn from the Midwest, Wallace was one of the most liberal of New Dealers and a strong believer in accommodation with Russia. As the anti-Communist rhetoric heated up after the war, he became pigeonholed by many politicians and most of the press as a wild idealist—one of the "post-war dream boys," as one government official labeled the liberals in government.
Truman, who made Wallace his commerce secretary, thought he was an indecisive intellectual more interested in studying foreign languages than in governing. Once he became a born-again anti-Communist, Truman fumed in his diary about Wallace, this "100 percent pacifist" who took up cabinet-meeting time telling everyone that he "wants to disband our armed forces, give Russia our atomic bomb secrets and trust a bunch of adventurers in the Kremlin Politburo." Truman wanted to get rid of him. He got his chance in late 1946 when Wallace gave a speech in Madison Square Garden skewering Truman's "get tough" policy against Soviet expansionism. A week after the speech, Truman demanded Wallace's resignation.
He got it and in the process split the Democratic Party. Wallace declared himself a third-party candidate for the upcoming presidential election. He and his backers, styling themselves the true followers of FDR, created the Progressive Party. Pauling's favorite political action group, the ICCASP, badly wounded after being attacked as a Communist front, reformed itself as the Progressive Citizens of America and took up the Wallace cause. At first, the Wallace campaign looked strong. He could be a forceful, intelligent speaker, and in 1947 his message of internationalism and revised New Deal policies played well to enthusiastic and well-attended rallies. The stadiums and halls where he spoke were filled with a polyglot of liberals and anti-Truman Democrats, with a sprinkling of Communists. Pauling liked Wallace's internationalism, his New Deal social consci
ence, and his intellectual approach to politics, and he joined the parade, becoming a member of a "Democrats for Wallace" group, assuming a national vice chairmanship of the Progressive Citizens of America, giving money to Wallace's campaign and introducing the candidate at a big Los Angeles rally. There Pauling and his daughter, Linda, shared the dais with Katharine Hepburn, who asked the gamine Linda why she wasn't in the movies.
Pauling and Wallace were alike in some ways, both given to solitary thinking, both passionate about ideals, both unwilling to compromise. Even better from Pauling's standpoint, Wallace, with his background in hybridizing agricultural stock, understood something about science. "I think he was a good, rational person who may have had some difficulty, the way scientists have, in being a politician," Pauling said.
That was the problem. Wallace, who always had trouble working up the energy to glad-hand and backslap, was too remote and cool to make a good politician. He was also unwaveringly accommodating toward the USSR. In early 1946 it had seemed reasonable to talk about turning over atomic bombs to the United Nations and funding the massive reconstruction of the USSR. By mid-1948, it was political suicide.
Wallace's candidacy had already begun sputtering when, while Pauling was in England in February and March 1948, a Communist coup in Czechoslovakia brought that country firmly into the Soviet orbit. Wallace charged that the Czech putsch was a response to a planned right-wing coup that may have involved the U.S. ambassador. Too quick to excuse Russia, too eager to criticize America, Wallace was lampooned by Republicans and crucified in the press. When it became clear that his candidacy was splitting the Democratic Party, threatening Truman’s re-election chances, many Democrats deserted the Progressives. Membership dwindled.
Pauling was in Washington State on election day, speaking about peace and chemistry near the government's huge Hanford facility, where the raw material for atomic bombs was processed. Despite the fact that Ava Helen, fearing a Republican victory, had defected to Truman at the last minute and encouraged Pauling to do the same, he stuck with his man, casting an absentee ballot for Wallace. When Pauling went to bed that night, the radio commentators were sure of a Republican victory. At two in the morning, Pauling awoke, went out to his car in the motel parking lot, turned on the radio for more news, and was relieved to hear that Truman had been declared the victor. Wallace's showing, however, was dismal: He received less than 3 percent of the popular vote, and the Progressive Party failed to carry a single state. Later, Pauling lamented, as would tens of thousands of Progressives, "Wallace may have been too honest to be a successful politician."
The 1948 election marked the end of Rooseveltian liberalism and the beginning of a new phase of intolerance in America. The Wallace candidacy had released Truman from any need to cater to the liberal wing of his own party and allowed him to move even further to the right. He had proven to himself that Democrats could win elections by getting tough on Reds, and he would continue to do it as long as it yielded victory.
The political landscape had clearly shifted, but Pauling did not move with it. Four years earlier, he would have been considered a typical New Dealer, a liberal Democrat hovering somewhere between center and left. His ideas had not changed—throughout 1947 and 1948 he continued to speak out for international control of atomic energy and against loyalty oaths, for civil liberties and against anti-Communist hysteria—but the nation had changed. Fear was driving politics now. Rooting out Communists became the national pastime. And fewer and fewer people would speak against it.
Not Any Bargain
As the mania for security grew, so grew FBI director J. Edgar Hoover’s power and influence. In the name of national security, Hoover collected information on groups, politicians, activists, and citizens private and public, dangerous and innocuous, filling cabinet after cabinet with thousands of fat files, indexed and cross-indexed, the dirt and the daily routine of everyone from legislators and lawyers to longshoremen and librarians.
One FBI file carried the name of Linus Pauling. In the winter of 1947, a few weeks before Pauling left for Oxford, Hoover's intimate associate Clyde Tolson showed his boss a letter received from a member of the American Chemical Society who was worried that the group's president-elect, soon to be leaving for England, might be subversively inclined. "A quick check of the files," Tolson told Hoover, "indicates that we have never investigated Pauling but that he is closely associated with the Progressive Citizens of America and signed a resolution for the abolition of the House Un-American Activities Committee [HUAC] and is a member of infiltrated groups . . . there are sufficient references to him to indicate that he 'is not any bargain.' "
Hoover may have wanted to investigate Pauling, but he could not. While the FBI's ability to gather information on Americans had been extended through the loyalty oath program to hundreds of thousands of federal employees, including professors who received federal grants and contracts, it was not unlimited. Pauling had not been involved in any classified research since the end of the war, had not applied for federal grants, and as a researcher in a private university was currently immune from scrutiny under Executive Order 9835.
That changed as soon as Pauling settled in London, where he was quickly approached by a representative of the Office of the Assistant Naval Attaché for Research. It was in America's interests to keep abreast of the state of British science, the young officer said, and it would be useful if Pauling could let the Navy know his impressions of the labs he visited—nothing proprietary, the officer told him, nothing that would involve breaking confidences, just his general observations of the state of British science. For his role as a consultant to the government, they would pay him fifty dollars a day. All that was required was that he sign a contract. The moment Pauling signed, he became subject to the loyalty program, and the FBI began reviewing his political history.
Much of the Bureau's work was easy, as Pauling never made a secret of any of his affiliations. The agents cross-checked his name in their files and came across a 1947 interview they had done with Pauling regarding the loyalty of J. Robert Oppenheimer, another scientist with a suspiciously liberal background. Pauling, who called himself a "close friend" of Oppenheimer's, told the FBI that Oppy was "volatile, complex and brilliant" and that he was certain of his loyalty to the United States. The discussion then turned to Oppenheimer's political activity, and Pauling began talking at length about his own work with the Association of Pasadena Scientists (APS), the ICCASP, the Progressive Citizens of America (PCA), and his support of Wallace. The interviewing agent noted in his report that a confidential source had called the Hollywood chapter of the ICCASP the "main political and propaganda pressure group of the Communist Party in California" and that the PCA was rife with Communists and Communist-fronters.
The FBI then borrowed the Pauling file HUAC had collected, rich with clippings from the Daily Worker and other Communist newspapers. There were "innumerable references," the FBI found, to Pauling's speeches on atomic policy and human rights. It was all suspicious, they thought, but the only proscribed activity under the rules of the loyalty program was Pauling's wartime flirtation with the National Council of American-Soviet Friendship, a group that had since been put on the attorney general's blacklist.
Still, it was enough for Hoover to order a full-scale field investigation. He asked the Office of Naval Intelligence to track Pauling's activities in England. He ordered FBI agents to check police and credit files and interview associates in Berkeley and Cornell. He had the Los Angeles FBI field office coordinate an investigation in Pasadena. Agents quizzed Pauling's coworkers, neighbors, and Caltech administrators. They were given permission to look through his private Caltech personnel file.
They found nothing. Everyone they spoke with defended Pauling's loyalty without reservation. His colleagues agreed that while Pauling was "very frank in his observations," "a joiner," and "an idealist who believed in the free expression of ideas," he was no Communist. The worst anyone would tell the FBI was that Pauling w
as "an exhibitionist" and "an intellectual parlor pink." The Los Angeles FBI office let the investigation drag on through the summer of 1948, until Hoover himself telegrammed that Pauling's was "among the most delinquent loyalty investigations in the Bureau." On September 10, a twenty-seven-page report was finally finished, and on October 14, Hoover forwarded it to the Civil Service Commission for further action.
He was too late. Pauling's contract with the Navy had expired on September 1, and he was no longer subject to Executive Order 9835. Its interest renewed by the FBI investigation, HUAC—still looking for a prime scientific target—might have mounted a public investigation if J. Parnell Thomas had still been in charge. But Thomas was gone, convicted of payroll padding and sent to prison just after the 1948 elections. Hoover tried another tack, sending Pauling's report to the attorney general's office for possible criminal action. The attorney general could find no violation of the law.
The FBI investigation was over by the time Pauling returned to the United States from Oxford. When he reached Pasadena, he heard from his colleagues the unnerving news that agents had been asking questions about him, but then agents were asking questions about a number of scientists at the time, especially those involved in atomic weapons research. Pauling shrugged it off.
Ironically, as Hoover was investigating Pauling's loyalty, others were honoring it. As the FBI worked to find some reason to bring him up on criminal charges, Pauling stood with four other faculty members at a special Caltech ceremony in October 1948 to receive a Presidential Medal for Merit, the highest civilian award given by the government. The citation, signed by Harry Truman, noted Pauling's "imaginative mind," his "brilliant success" with rocket powders and explosives, the oxygen meter and serum substitutes, and his "exceptionally meritorious conduct in the performance of outstanding service to the United States." Pauling was extremely proud to receive the honor.
