Force of Nature- The Life of Linus Pauling
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But to Pauling, vitamin C was a nutrient, not a drug. When the medical researchers saw a small effect, he thought the logical next step should have been to follow up with larger doses. His literature search uncovered at least one study that showed what might happen if they did. In 1961 a Swiss researcher named Ritzel had given half of a group of 279 skiers 1,000 mg per day of vitamin C—more than five times the Minnesota dose—and the other half a placebo. Ritzel found that those skiers receiving ascorbic acid had 61 percent fewer days of illness from upper respiratory tract infections and a 65 percent decrease in the severity of their symptoms compared to the placebo group.
This, Pauling thought, was very strong evidence in favor of his ideas. Plot the dose of vitamin C along the bottom of a graph and the effects on colds up the side and you could draw a straight line from the Minnesota results (a small effect with small dose) to the Swiss findings (a larger effect with larger dose). He found a few other papers in which the results fit the pattern. True, some of the research he looked at showed no effect at all—most of these studies, Pauling estimated, were flawed because they used too low doses, too short duration, shoddy oversight, or improper blinding—but the important thing was that a small group of careful clinical studies existed that supported Pauling and Stone's general theory of vitamin C and health: The more C you took, approaching megadose levels, the lower your chances of getting sick, and the less sick you got. Although Pauling's literature review also turned up hints of ascorbic acid's beneficial effects on a number of other diseases, everything from heart disease to polio to cancer, the common cold was the best-documented example of its effects.
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In the spring of 1970, Pauling decided to go public with his findings.
He did not feel he could wait. He had, he thought, good evidence that a cheap, apparently safe, easily available nutrient could prevent at least an appreciable fraction of a population from suffering through an affliction that made millions of people miserable. And there might be even greater results. Pauling had read of small villages, snowbound in the winter, where no one got colds because there was no reservoir of respiratory viruses to pass around. When visitors arrived in the spring, they would bring colds with them, and everyone would suffer. What if, through the use of vitamin C, a great many more people strengthened their resistance to colds? The two hundred or so cold viruses rampant in the world would have many fewer places to replicate themselves. The spread of colds would lessen; the population of cold viruses would decrease. "If the incidence of colds could be reduced enough throughout the world," Pauling thought, "the common cold would disappear, as smallpox has in the British Isles. I foresee the achievement of this goal, perhaps within a decade or two, for some parts of the world." Vitamin C, properly and widely used, might mean the end of the common cold.
This, of course, would not only greatly lessen the amount of suffering in the world; it would increase the fame of Linus Pauling. He was nearing seventy years of age. It had been nearly twenty years since he had captured international attention with the alpha helix and won the Nobel Prize for chemistry. There had been talk at that time of a third Nobel Prize in physiology and medicine for his sickle-cell work, but it had not materialized. His efforts had gone to politics in the years since, and none of his recent scientific work had had much impact. Science was moving on without him. He was becoming a historical figure.
Pauling did not feel like one. He was not ready for emeritus status, trotted out at honorary occasions, shunted aside while the young men made the discoveries. He was still strong, still smart, still a fighter. Orthomolecular medicine was the newest of his grand plans, and no one had shown that his ideas about creating an optimal molecular environment for the body and mind were wrong. The evidence he had uncovered about ascorbic acid and colds, evidence that showed human health could be improved by increasing the amount of vitamin C in the body, was the strongest indication yet that he was right. Bringing it to the public's attention would not only be good for the public; it would be a striking example of the correctness of his general theory.
On March 31, 1970, he signed a contract with his longtime textbook publisher, W. H. Freeman & Co., to produce a short book on the common cold. This was to be the popular explication of his ideas, a direct—and possibly profitable—communication to the public along the lines of No More War! While working on it at the ranch in Big Sur over the next two months, he also drafted a more technical version of his findings to be submitted to Science.
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Pauling's book Vitamin C and the Common Cold, written in his usual clear, well-organized, straightforward style, presented the results of his literature search. He discussed the findings of five controlled trials that supported his idea, several anecdotal instances of physicians who had treated colds with vitamin C, and evidence that ascorbic acid was safe in large doses. Pauling felt confident that a several-gram daily dose would do no more harm than to cause loose stools, that vitamin C was safe, especially compared with potentially toxic, commonly available over-the-counter medications such as aspirin. The rest of the book was a summary of his orthomolecular thinking and Stone's ideas about evolution. A good deal of space was devoted to the topic of biochemical individuality, which resulted in a wide personal variation in the need for vitamin C and other nutrients.
On November 18, 1970, prepublication galleys were released to the press, and an unprecedented public roller-coaster ride began. The next day, the New York Times quoted Pauling as saying that humans needed between 1 and 4 grams of vitamin C per day to achieve optimal health and prevent colds. Pauling also took the occasion to slam the medical establishment—from drug companies to medical journals and physicians—for attempting to quash the evidence in favor of ascorbic acid. Why would they do that? the reporter asked. Look at the cold remedy industry, Pauling said: It was worth $50 million per year, and that bought a lot of advertising space in medical magazines.
This quickly alienated both physicians and the editors of medical journals, neither of whom liked the implication that profits were more important than health. The medical establishment felt it necessary to respond, and respond quickly, once they saw how Pauling's idea took off.
The book sold wildly, and so did vitamin C. Pauling's timing, at least on the public side, was superb. The 1960s had seen a resurgence of interest in "natural" health based on a holistic attitude that said body, mind, and soul were one. Many streams fed into this alternative health movement: a back-to-the-land, organic-foods orientation; a fascination with yoga, acupuncture, meditation, and other Eastern health practices; the rediscovery of the lost Western arts of naturopathy and homeopathy. Pauling's message about vitamin C resonated with millions of people who were reacting against corporate, reductionistic, paternalistic medicine, with its reliance on drug therapy, with people taking a renewed responsibility for their own health and trying to do it naturally. It was delivered just as natural food stores were popping up on corners in every town in America, each one stocked with a section for herbal remedies, a rack for magazines on alternative health regimens, and plenty of shelf space for vitamins.
The publication of Pauling's book triggered a nationwide run on vitamin C. Sales skyrocketed, doubling, tripling, quadrupling, within a week of its appearance. Druggists interviewed in newspapers across the nation told of people coming in to buy all the vitamin C they had. Wholesale stocks were depleted. "The demand for ascorbic acid has now reached the point where it is taxing production capacity," said a drug company spokesman less than a month after Pauling's book appeared, adding, "It wouldn't pay to increase production capacity since we're sure it's just a passing fad."
The reaction was swift. The physician-head of the Food and Drug Administration (FDA), Charles C. Edwards, announced to the press that the national run on vitamin C was "ridiculous" and that "there is no scientific evidence and never have been any meaningful studies indicating that vitamin C is capable of preventing or curing colds." The FDA, Pauling found, had proposed in 196
6 that no vitamin C tablets over 100 mg be available without a prescription, and he responded to Edwards with sarcasm. If the FDA had its way and he wanted to take 10 grams of vitamin C to fight off a cold without going to a physician for a prescription, Pauling said, he would have to take 100 tablets. "I think I would have as much trouble swallowing all these tablets as I would swallowing some of the statements made by the Food and Drug Administration in proposing these regulations," he said.
The medical press was equally critical of Pauling. The American Journal of Public Health said that Pauling's book was "little more than theoretical speculation." The Medical Letter launched a harsh attack, saying Pauling's conclusions "are derived from uncontrolled or inadequately controlled clinical studies, and from personal experience" and pointing out that there was no good evidence that vitamin C was safe when taken over a long period of time in large doses. Finally, and damningly, the Journal of the American Medical Association passed judgment, writing of Pauling's book, "Here are found, not the guarded statements of a philosopher or scientist seeking truths, but the clear, incisive sentences of an advertiser with something to sell. . . . The many admirers of Linus Pauling will wish he had not written this book."
Pauling could do nothing about the aesthetic judgments of book reviewers, but he could fight errors of fact. "I ask that you publish a correction, retraction, and apology of the false, misleading, damaging and defamatory statements made about my book," Pauling began a twelve-page missive to the head of the Medical Letter's editorial board. He rebutted their article point by point, stressing that he had cited perfectly adequate controlled trials, from the Swiss and Minnesota studies to a 1970 Irish report of a double-blind trial of more than 100 schoolgirls that showed that 200 mg per day of ascorbic acid during the winter significantly reduced the incidence, duration, and severity of colds. As for the safety of megadoses of vitamin C, all of the evidence to date showed that the worst a high dose could cause was mild stomach irritation or diarrhea, which could be controlled by monitoring the dose and building up tolerance gradually. He challenged the journal to bring forward any case in which someone taking large doses of vitamin C had been harmed by it.
None were forthcoming, but neither was an apology. Instead, the Medical letter piece was picked up by the popular press, including Consumer Reports, which reiterated the Medical Letter's points, roundly condemned Pauling's book, and added that in the absence of more safety data, Pauling's actions were not "socially responsible." The Paulings, who had subscribed to Consumer Reports for decades, were shocked by the harsh tone of the piece, which Pauling called "intemperate and completely unreliable." They argued their point in a meeting with the president and members of the board of directors of the magazine's sponsoring body, but a correction was never published.
Bad news came from the journal Science as well, which rejected Pauling's paper on the evolutionary need for vitamin C. Pauling immediately sent it to the Proceedings of the National Academy of Sciences, where he knew that as a member of the NAS there was no doubt of his getting it published.
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The controversy over Pauling's book arose from a simple fact: He had not made his case. The book was a combination of his interesting but unproven speculations about orthomolecular medicine and the human evolutionary need for ascorbic acid, coupled with a select handful of studies that indicated that vitamin C could prevent or ameliorate colds in a fraction of a population. That might make an interesting conference paper, but it was little reason to advocate a wholesale change in the dietary habits of a nation. His critics pointed out that he had no clear theory of how vitamin C exerted it powers and that there was no good study—no study at all—establishing that the long-term ingestion of megadoses of vitamin C was safe. The current dogma in the medical profession was that vitamins were needed only in the small amounts provided by a well-balanced diet. Taking grams of vitamin C every day might cause everything from gastric upset to kidney stones, and who knew what else?
The way he had gone about publicizing his ideas, sidestepping the normal channels of scientific peer review to publish a popular book, also fueled criticism. He was behaving like a health faddist, not a scientist. In the eyes of most physicians—generally conservative about new therapies, disdainful of the holistic health movement, trained to believe that vitamin C was needed only to prevent scurvy—Pauling looked like a nutritional quack, a vitamin pusher who was essentially prescribing without a license.
Sure, he was a Nobelist, but most physicians did not know much about his illustrious scientific career. He was old, he was out of his field, he was obsessed with vitamin C and convinced he could not be wrong. Victor Herbert even diagnosed the case on television: Pauling, he said, suffered from something like senile megalomania.
It was the medical profession's duty to shut him down.
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The debate over Vitamin C and the Common Cold raged through 1971. To every charge leveled by the medical profession, Pauling found an answer. No, he did not know exactly how vitamin C prevented colds, but there was evidence that it had antiviral and immune-building powers, and in any case, as he wrote in the book, "we may make use of ascorbic acid for improving health in the ways indicated by experience, even though a detailed understanding of the mechanisms of its action has not yet been obtained." All of the published literature showed that high doses of vitamin C over an extended period of time were benign. The worst that happened was transitory diarrhea or stomach upset that could be controlled by increasing intake slowly. There was not one proven case of kidney stones resulting from vitamin C. The FDA made a great deal of the danger of taking one form of it, the sodium ascorbate salt, because it could put too much sodium into the diet, but that was easily countered by taking the more common nonsalt form of pure ascorbate. The specter of long-term health problems was, Pauling felt, a red herring. Besides, he pointed out, physicians had no trouble telling patients to take aspirin, another substance without a defined mechanism of action and one that had been proven much more toxic than vitamin C. As for his method of publication, he had tried to get his ideas published simultaneously in a juried journal, Science, and had been turned down. But the promise offered by vitamin C to aid human health was too great—and Pauling's age was too advanced—to wait for the normal channels of scientific communication. He went public to help the public. Physicians might think of doing the same thing.
In his counterattack, Pauling stressed two things. The most important was that rather than touting a miracle cure for the common cold, he was simply promoting a strategy to control it. From the beginning he stressed that individuals varied widely both in their natural resistance to colds and their need for vitamin C. Some lucky people never developed colds whether they had vitamin C or not. Others apparently remained susceptible to colds regardless of how much they took. These two groups, the immune and the highly susceptible, were at the ends of a bell curve. In the middle were the great majority of people, and Pauling believed that the evidence showed firmly that it was here that vitamin C could help increase resistance. He wanted to shift the bell curve, make millions of people less miserable, and help decrease the total sum of human suffering.
In this he was being hampered, he believed, by the medical profession's drive to make money and their tendency toward conformity. Physicians were too busy earning their fees, he said, to read carefully the literature on vitamin C, so they relied on the pronouncements of experts in their own field like Stare and Herbert. "They are willing to make their statements without ever going back to see just what the facts are," Pauling told a journalist. "They just pick up bits of information or misinformation from one another, the authorities, instead of checking the facts and drawing their own conclusion."
This was an argument, in other words, not only over scientific facts but over worldviews. Meanwhile, the book sold so well that a paperback edition was quickly arranged, for which Pauling added two new chapters specifically responding to his medical critics. His belief in ascorbate wa
s even stronger now because he had taken a closer look at the data to answer some points. He found that even if he accepted only those trials that best conformed to the physicians' own definition of proof—double-blind trials (ones in which neither the patient nor the physician knew during the test who was getting the placebo and who the test substance)—and adding his own stricture that they involved doses of more than 100 mg of vitamin C per day and tracked naturally occurring colds over a long period of time, the evidence was "overwhelming": The four published trials that met the qualifications all showed that vitamin C had a significant effect in preventing and ameliorating the common cold. The right thing for the medical profession to do now was not to argue the point but to investigate it fully with well-controlled trials of high-dose vitamin C.
By the time the paperback edition appeared in December 1971, sales of vitamin C began soaring again as the winter cold season hit. Not all the evidence was in Pauling's favor. At the University of Maryland, researchers announced the results of a study in which eleven prisoners were given a Pauling-sized dose of ascorbic acid, 3 grams per day for two weeks, before inoculating them with cold viruses. All eleven developed colds, as did the ten controls who received a placebo. The Maryland study was widely reported as proof that Pauling was wrong—despite the fact that there was no indication that the small-scale study was double-blind and the report had surfaced at a scientific meeting, not in a juried journal. Pauling dismissed it for other reasons, because the prisoners had been hit with an artificial inoculation of viruses that could well have been great enough to overwhelm any protective system in the body, whether reinforced by vitamin C or not.