by Thomas Hager
In other words, to Stone, giving someone enough vitamin C to prevent scurvy was like feeding them just enough to keep them from starving. Full, robust health demanded more. He advised that Pauling start with about one and a half grams per day. It was especially good, Stone said, for preventing viral diseases like colds.
"I didn't believe it," Pauling later said jokingly of Stone's letter.
After all, Stone was no physician, nor was he a nutritionist exactly or a professional medical researcher. His background had been in the brewing industry as a biochemist. But Stone's theoretical framework—the idea of a genetic mutation causing the need for vitamin C—was directly in line with Pauling's own thinking. Beadle had shown with his Neurospora mutants how genetic mutations led to variants with new nutritional requirements for vitamins and amino acids, and Pauling had taken Beadle's ideas to heart. "Every vitamin we need today bears witness to a molecular disease our ancestors contracted some hundreds of millions of years ago," Pauling had written in 1962. A year or two earlier, he might have ignored Stone's advice as just another crank fan letter, but now, especially given his recent awakening of interest in megavitamin therapy for schizophrenia, vitamin C seemed at least worth a try.
He began taking 3 grams per day.
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The results were miraculous. Colds had for decades been the bane of Pauling's existence, and the colds he caught never seemed to be mild. They were debilitating, hacking, phlegm-drenched affairs that put him in bed for a week. Then many of them would progress to full-blown sinus infections. Colds interfered with his work, forced him to put off travel plans, made his life miserable. In the past, he had found only one way to prevent them—a daily dose of penicillin, a practice he followed off and on for years, from 1948 until the early 1960s.
Then came vitamin C. After starting to take it at Stone's recommended levels, he and Ava Helen both found that they had greater energy, an increased sense of well-being, and no more colds. This cure for a condition that had plagued Pauling for four decades, as much as anything written in the scientific literature, made Pauling a believer in vitamin C.
But he was a quiet believer. For three years he took his vitamin C every day and enjoyed the benefits without writing a word about it. Not that he was not interested in it from a biochemical standpoint; he even started measuring the vitamin C in his urine while at Santa Barbara—but he was less interested in ascorbate as a cure-all than he was in expanding Hoffer and Osmond's ideas about mental health and vitamins.
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Pauling was now synthesizing another great theory, a grand plan of the mind that occupied his imagination for the next year. Hoffer and Osmond's use of megavitamins in treating schizophrenia was the catalyst, but there was more to it. The mind, Pauling had concluded after years of research, was a firestorm of molecular-electrical energy firing a complex biochemical system fed by metabolites, governed by enzymatic reactions, and orchestrated in some as yet unknown way—most likely, Pauling thought, following the most advanced current thinking, by the creation of favored patterns of neuronal connections.
His interest centered on the underlying biochemical system. His first forays into the mysteries of the mind, his studies a decade earlier on mental deficiency and PKU patients, had focused on discovering and defining enzyme deficiencies that would explain the molecular causes of mental deficiency. The tools he had used, urinalysis and blood analysis, had been too crude to find what he was looking for; the search had ended in failure. But now, in late 1966 and early 1967, he broadened his approach. Another overarching theory was emerging from his renewed interest in mental health, one that he believed would explain—like all of his great theories—a variety of confusing, sometimes contradictory, observations.
If mental functioning depended on the presence of the correct amounts of certain molecules—enzymes, coenzymes, substrates, and products—then optimal mental functioning was likely to depend on maintaining some type of molecular balance in the brain, "the right molecules in the right amounts," as he would later say. If one important enzyme was inactive or malfunctioning—as in PKU patients—it could throw off the entire mechanism. The effects of a poorly functioning enzyme could, however, be counterbalanced by a great increase in its substrate. This might be what Hoffer and Osmond had done with niacin—greatly increased the substrate or cofactor needed in a malfunctioning enzymatic reaction to push it in the right direction.
He came up with a catchy new name for his theory, "orthomolecular" psychiatry, and began preparing his ideas for publication.
"Orthomolecular psychiatric therapy is the treatment of mental disease by the provision of the optimum molecular environment for the mind, especially the optimum concentrations of substances normally present in the human body," he explained in his first paper on his theory, written in the spring of 1967. The treatment of PKU with a protein-free diet was one example of orthomolecular therapy: The result was a lowering of the concentration of the amino acid that caused mental problems. Hoffer and Osmond's megavitamin therapy was another. There were others. It was known that a variety of nutritional deficiencies, including vitamin deficiencies like pellagra and scurvy, could lead to mental derangement of various sorts. "The functioning of the brain and nervous tissue is more sensitively dependent on the rate of chemical reactions than the functioning of other organs and tissues," Pauling wrote. "I believe that mental disease is for the most part caused by abnormal reaction rates, as determined by genetic constitution and diet, and by abnormal molecular concentrations of essential substances."
There was something tremendously exciting to Pauling about this new theory. It was an important theory, yes, one that postulated an entirely new way of looking at the optimal functioning of the mind, but there was more to it than that. It offered a way of going back and helping understand, in some way correct, something irrational and incomprehensible in his life. He remembered his mother, Belle, pernicious anemia eating away at her mind, pushing her into a mental ward. She had suffered a molecular imbalance in her brain. Orthomolecular psychiatry could help make sure that did not happen to anyone else.
And there was more. The orthomolecular concept could be applied to the entire body. Diabetes, for instance, could be seen as an orthomolecular disease, treatable by providing the right amount of a naturally occurring molecule, insulin, to the patient. Goiter was treated by providing needed iodine. Fluoridated water could prevent cavities. Life was a complex series of chemical reactions; the body was the vessel in which they took place. Like any chemical reaction, everything depended on having the right amounts of starting material, catalyst and product. Pauling quickly expanded his theory from the brain to an all-encompassing orthomolecular vision of health.
San Diego and Stanford
Pauling now needed a laboratory to test his theory, a facility that would help him get grant funding. Santa Barbara could not provide him one, so he looked elsewhere. In the summer of 1967, an opportunity arose at the new and growing UC campus at San Diego, to which Pauling had been invited as a one-year visiting professor of chemistry and physics. The San Diego chemistry department seemed interested in allowing this visit to evolve into a permanent appointment. Pauling took a leave of absence from the CSDI, Ava Helen found a house in La Jolla, and in September 1967, Pauling started to work at San Diego.
For a while it seemed like a return to happier days, with a laboratory—a tiny fraction of the space he had at Caltech but still a laboratory—scientific colleagues to work with, and the reassuring rhythm of the academic calendar.
San Diego, however, would prove no more secure a resting place than Santa Barbara. Pauling had barely cobbled together some research funds and hired a research assistant to work on some problems when it became apparent that his chances of a permanent appointment were in trouble. The reason again was politics.
Disgusted by the Vietnam policies of both major political parties, Pauling had become vehemently more radical. In 1967 he joined the Peace and Freedom Party—its presid
ential nominee was Black Panther Eldridge Cleaver—and adopted the rhetoric of the left-wing Students for a Democratic Society (SDS), whose aims and tactics he applauded. He supported Black Power. He called for continued and vigorous mass demonstrations. And he now talked of revolution. "I believe in nonviolence," he told an antiwar rally in May 1968. "But The Establishment believes in violence, in force—in Mace, napalm, police power, aerial bombing, nuclear weapons, war. As long as the selfishness of the Establishment remains determinative, our hope that the coming revolution will be nonviolent has little basis in reality."
His escalating rhetoric brought him again to the attention of the UC regents. There had been rumors from the time he arrived in San Diego that a few regents, the usual longtime Pauling critics, would never agree to a long-term appointment for him at any UC school. Then an added difficulty arose when he celebrated his birthday in February 1968. The age he had now reached, sixty-seven, was the standard retirement age for UC professors. Pauling was in perfect health, bursting with ideas, and had not given much thought to retirement. But age was now used as a factor to hold up his reappointment. At the same time, a rule change went into effect giving the UC board of regents direct power to veto any exception to the retirement-age rule, and it was clear to Pauling that the regents would never support him. His future at San Diego was now in limbo, which made it difficult for Pauling to secure grants. Without grants, he had little chance of being seen as a productive faculty member, one worth keeping on after retirement age.
After months of hesitation and internal squabbling, UCSD finally reappointed Pauling for a second one-year stint a few weeks before the start of fall term, in 1968. But it was clear now that anything beyond one year was unlikely. Pauling began looking for other places to go. He considered, then rejected, an offer from his old friend Beadle to come to the University of Chicago. His home was in California
In February 1969, Pauling announced that he was leaving San Diego at the end of the academic year. His destination, he said, was Stanford University, where he had been offered an appointment as a consulting professor in chemistry, starting in July.
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In May 1969, hundreds of San Diego students gathered in a school gymnasium to mourn the death of a Berkeley student who had been killed by police gunfire during the confrontation over the People's Park. The question at hand was whether to go on strike and shut the campus down.
Some faculty members pleaded moderation. Then Pauling came to the front of the gathering. His voice as strong as it had been in his antitesting speeches, his sentiments clear, he told the students that the Berkeley killing was part of the pattern of U.S. militarism, economic exploitation, and disregard for human rights that was being played out in Vietnam. "The strike is a way for exploited and suppressed people to express their objection to the exploitation and suppression," he cried, his voice growing stronger as he went along. "Everyone in the whole University of California, all the students, the faculties, the employees, should strike against the immorality and injustice of the act at Berkeley."
It was his way of saying good-bye to the regents of the University of California.
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Stanford was a great improvement in several ways. Palo Alto was much closer to the ranch at Big Sur, for one thing, making his and Ava Helen's frequent trips there less onerous. The chemistry faculty members were happy to have him, there were no problems at the private school with his retirement age or with regents, and the San Francisco-area political climate was amenable.
But financial considerations had forced Pauling to strike a deal in which he paid half of his own salary and all of his expenses out of his own research grants. There was no guarantee of any salary at all after the first year. And the only laboratory space available was small and separate from the main chemistry building.
But once grant money started coming in for his orthomolecular work, he thought, all that could be improved. Pauling and Ava Helen found an unassuming and comfortable house, with a big rock fireplace and natural-wood highlights—in a way much like their old house in Pasadena—in Portola Valley, in the hills five miles west of the university.
Perhaps now, he thought, he could quit wandering, settle down, and make some significant advances in his work.
CHAPTER 23
Vitamin C
The End of the Common Cold
Pauling did not dislike physicians. For the most part, however, he did not respect them.
Part of the reason became clear to him in the late 1950s, when he gave a dinner talk about molecular disease to the San Diego Medical Association. He was mildly irritated during his lecture by the way the doctors continued conversing and clinking their glasses while he spoke. Then afterward, when he and Ava Helen attended a reception at the home of one of the association's officers, they overheard someone commenting that since Pauling had agreed to speak without a fee, the group could now afford to pool their money and bring in a really outstanding physician as a speaker next month. The Paulings were both insulted and enlightened about the priorities of the medical profession. "The result of our having overheard this discussion was that I decided that I would not accept invitations from organizations of physicians unless they were accompanied by an offer to pay a stipend or honorarium comparable, in my judgment, to what they would have paid a physician," he said.
The medical profession's attitude toward money was only part of the problem. It seemed to Pauling that physicians were also in some cases unable to fully appreciate the value of their own research findings, an inability that became critical in Pauling's decision to involve himself in a public debate over vitamin C.
He had been generally silent about ascorbic acid and its benefits through the late 1960s, limiting his few comments to ideas about how it might be used, along with other nutrients, in the treatment of schizophrenics. In late 1969, however, convinced by the theoretical arguments of Irwin Stone and impressed by his own success in preventing colds, Pauling began expanding his comments to include the subject of ascorbate and general health, noting in a speech he gave to physicians at the Mt. Sinai Medical School his success with the use of vitamin C as a cold preventive. His comments were reported in the newspapers, and afterward he received a "very strongly worded" letter from Dr. Victor Herbert, a leading clinical nutritionist and a man who helped set the U.S. recommended daily allowances (RDAs) for vitamins, who assailed Pauling for giving aid and comfort to the quacks who were bleeding the American public with unsupported claims about the benefits of vitamins. Where, Herbert asked, were the carefully controlled clinical studies to prove that ascorbic acid had a real effect on colds?
Pauling was taken aback. He had not, in fact, carefully reviewed the literature on vitamin C, limiting his reading to a few of the citations in Irwin Stone's original papers. But now, "sufficiently irritated by this fellow Herbert," he began a typically comprehensive tour of the scientific journals.
At the same time, a writer for Mademoiselle magazine contacted Pauling to get his comments on vitamin C for an article on its health benefits. Pauling offered the general observation that "optimal amounts of vitamin C will increase health and intelligence" and referred readers to his paper on orthomolecular psychiatry. When the article appeared in November 1969, he found his statement rebutted by Frederick Stare, a professor of nutrition at Harvard, who said Pauling "is not an authority on nutrition" and that there was no evidence that increased C helped prevent the common cold; in fact, just the opposite was true. A large-scale study done with five thousand students in Minnesota twenty years earlier, Stare said, had proven definitively that vitamin C had no effect on colds.
Stung, Pauling quickly tracked down the study and found that Stare had gotten his facts wrong. The 1942 University of Minnesota study Stare referred to involved 363 student subjects who had been given either a placebo or some extra ascorbic acid over a period of twenty-eight weeks. It was true that the authors had concluded in their summary that there was no "important effect" of vitamin C on inf
ections of the upper respiratory tract. But when Pauling took a closer look at their data, he decided they were wrong. Despite what Pauling considered the very low dose of vitamin C given the students—an average of 180 mg per day compared to the 3,000 mg Pauling was now taking—the researchers had in fact seen an effect: Subjects receiving the extra vitamin had 15 percent fewer colds, and the colds they got were 30 percent less severe than those receiving the placebo. Vitamin C was not a preventive or cure, but the results were, Pauling estimated, statistically significant.
It was confusing, especially when Pauling saw the same thing happening in other reports he found on vitamin C and colds: Partial effects were discounted. The physicians who ran the studies seemed to be looking for total cures, not an indication of an effect. The doses they used were low (150-250 mg was common in these early studies— several times the current RDA but many times lower than what Pauling and Stone considered a protective dose), and the effects they looked for were too strong.
The problem, Pauling decided, was that the researchers were looking for vitamin C to act like a drug. In traditional drug testing, small differences in dosage could have tremendous effects, and overdoses were deadly. The tendency was to use relatively small amounts and look for big effects.
