by Thomas Hager
The general public believed Pauling. Overall demand for vitamin C shot up 15 percent in 1971, a rate three times faster than expected. By the mid-1970s vitamin C was by far the biggest seller in the burgeoning vitamin market, with an estimated 50 million Americans taking at least some extra daily supplementation. The very happy manufacturers of vitamin C labeled this "the Linus Pauling Effect."
The Vale of Leven
While the medical profession in general dismissed Pauling's work, his arguments struck a chord with at least some individual physicians. Pauling received a steady stream of letters from practitioners who had seen positive effects in their patients who took extra vitamin C or who found that a gram or two helped them fight their own colds.
And it went beyond colds. In November 1971, Pauling received a letter from Ewan Cameron, a surgeon who practiced in a little hospital called the Vale of Leven outside Glasgow, Scotland, describing some amazing results he had seen when using high-dose ascorbic acid in the treatment of cancer. Very high doses, 10 grams per day or more, he wrote, seemed to slow the progress of cancer, in some cases even shrinking tumors. He had only tried it on a small number of terminal patients, but he thought Pauling might be interested in his preliminary work because he also had an idea about ascorbate's mechanism of action. Cameron had proposed in a book five years earlier that vitamin C might play a role in strengthening the interstitial ground substance, the thick, gel-like, collagen-reinforced mucopolysaccharide that acted as the glue holding cells together in the body. A strong ground substance was important in keeping cancer in check, Cameron hypothesized, because tumors tended to invade the body by breaking down the glue between normal cells. The stronger the glue, the less invasive the cancer and the more easily controlled and treated.
Cancers defeated this natural protective mechanism, Cameron wrote Pauling, by producing an enzyme, hyaluronidase, that dissolved the ground substance and opened the way to invasion of the body. Vitamin C helped defeat cancer by helping form an antihyaluronidase molecule. Details of this theoretical scheme had to be worked out, but Cameron was excited about his findings and the clinical results he had seen in his small group of terminal patients. He was as much an enthusiast about vitamin C as Pauling was. "I am unashamedly optimistic that with your help we could soon conquer cancer," he wrote Pauling.
Pauling was impressed by Cameron's findings and eager to explore this new clue about vitamin C's mode of action. Strengthening the substance that held cells together could account not only for a few studies that indicated vitamin C had an anticancer effect but also fit with what was known about scurvy (where one symptom was the breakdown of tissues, bleeding of gums, and so forth) and observations as wide-ranging as the fact that vitamin C seemed to help people with slipped discs. Vitamin C might be an overall tissue strengthener, a substance that helped bind the body together.
He began corresponding with the Scottish surgeon and quickly established that Cameron was no kook. Mild-mannered and capable, Cameron was a graduate of the University of Glasgow medical school and a fellow of the Royal Colleges of Surgeons of Edinburgh and Glasgow. He had treated cancer efficiently as a surgeon for many years and had published a number of papers on cancer treatment. The 1966 book he had written, Hyaluronidase and Cancer, had been well reviewed. After reading it, Pauling wrote Cameron, "I am tremendously interested to learn about the observations that you have made. ... I feel that your ideas are really important and supported by much evidence."
A month later, a less promising note from Scotland arrived. "We seem to have had several days of unmitigated clinical disaster over here," Cameron wrote. Three of his small group of vitamin C patients had died within seventy-two hours for various reasons—one from massive hemorrhaging, caused perhaps by the vitamin C working so well that the tumors self-destructed, kicking off the bleeding, Cameron wrote. His initial enthusiasm suddenly turned to doubt. Cameron wrote, "It is becoming obvious that even if ascorbic acid 'works' the associated clinical problems are going to be considerable but hopefully not insurmountable."
Pauling responded by urging his new colleague to continue his efforts. "The attack you are making on the cancer problem is the most important and promising of all those that I have heard about," he wrote Cameron. "It is essential that a thorough test be made of the value of ascorbic acid." Something should be published about this exciting new theory as well. The best way, he wrote Cameron, would be to conduct a double-blind test in his terminal patients, giving some vitamin C and others a placebo. But Cameron refused. After the small cluster of deaths, the remaining vitamin C patients in his original cohort and new ones that he added to the list continued to do better than expected. He felt now that it would be ethically wrong to do anything but provide all his terminal patients with vitamin C.
Even without a double-blind trial there was enough to publish, Pauling thought. As with the work on vitamin C and colds, he felt that Cameron's work with vitamin C and cancer needed to be made public as quickly as possible in order to spur further studies.
Pauling helped Cameron refine and write up his hyaluronidase theory and a review of his success with cancer patients for publication in the United States, and they decided as joint authors to submit it to the Proceedings of the National Academy of Sciences, a perfect vehicle for the paper not only because it would be published more quickly than in most journals but also because there was no chance of rejection. The journal's policy had long been that if someone was good enough to get into the NAS, he or she was good enough to publish ideas without peer review. The only member-submitted articles that had not been published in the past half century had been two or three that directly attacked the work of another NAS member—this was considered less than gentlemanly—and one less than adequate paper submitted by a member who had recently suffered a stroke. Everything else saw print.
So it was a complete shock a few weeks later when Pauling received a letter from John Edsall, the head of the PNAS editorial board, informing him that the journal was rejecting the cancer paper. The decision had been reached, Edsall wrote, at a stormy meeting of the editorial board in which it had been decided that papers advocating therapeutic procedures in areas as controversial as cancer treatment belonged in medical journals, where they could be better evaluated. Edsall himself had been the deciding factor. He had known Pauling for forty years and respected him greatly—it had been Edsall who defended Pauling's alpha helix at the Royal Society meeting in 1952—but he was also the son of a physician who had impressed upon him the importance of not implying great value in a treatment without a thorough and exhaustive examination of the evidence. He did not see that sort of care in Pauling and Cameron's paper. "It was a very troubling and quite painful decision," Edsall later recalled.
It was also unprecedented. "I do not know what to do next," Pauling wrote Cameron after hearing the news. "I do not have any idea about its publication in the United States. I have published nothing in the medical journals, and I have little confidence of being successful."
Pauling and Cameron finally tried resubmitting the piece to the PNAS, slightly altered to play down the therapeutic recommendations.
It was rejected again, this time with the backing of the council of the academy. Meanwhile, rumors of the extraordinary PNAS rejection filtered out into the scientific community and came to national attention when a news review of the controversy ran in Science in early August. The story reinforced the impression that Pauling had lost sight of science in his enthusiasm for vitamin C. Why else would the Proceedings, which never rejected any paper, reject his?
The only good thing to come of this latest controversy was an offer from a sympathetic editor of Oncology, a journal for cancer physicians, to publish the piece. Pauling and Cameron accepted eagerly.
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The incident seemingly did nothing to dampen Pauling's enthusiasm. Cameron continued to find that vitamin C helped his terminal cancer patients live longer, with less pain and more energy. It improved their quality of life
. And there were rare cases where it seemed to do more, where the cancer disappeared almost entirely after high-dose vitamin C therapy. Buoyed by anecdotal reports like this and continuing to find old reports of ascorbic-acid therapy as useful in other conditions, Pauling now asserted his belief that vitamin C in high doses was of likely value in "almost every disease state," as he wrote Cameron. "I do not think of it as being a wonder drug," he added, not an immediate cure for diseases, but at optimal doses it was a strengthener of the body's tissue structure and immune system, making it more likely that diseases could be fought off or their symptoms eased. It was valuable orthomolecular therapy to counter a genetic lack of ascorbate in the body. It was a tonic for a vitamin C-starved animal.
Pauling was convinced that vitamin C was effective. Now all he had to do was the research to prove it.
The Institute
Art Robinson was a bright young freshman at Caltech around 1960 when he took freshman chemistry. The class was then being taught by Jurg Waser, but Robinson sometimes saw Pauling deliver a guest lecture. Everybody knew vaguely about Pauling and his reputation and his fight against the U.S. government, and here he came striding into the lecture room, tall, ramrod-straight, a sort of chemist's Don Quixote trailed by his Sancho Panza, Waser, struggling under a load of props and models. To the students, Pauling was a legend. One day when they knew he was coming in, someone scrawled on the blackboard behind his podium, "Pauling is God and Waser is his Prophet."
Pauling saw it, paused for a moment, Robinson remembered, erased the words "and Waser is his Prophet," and continued his lecture.
That made an impression on everyone and a strong impression on Robinson. Two years later, when he was offered the chance to work on Pauling's anesthesia project, he jumped at it. Even as an undergraduate, the young man displayed a marked talent in the laboratory, where he helped devise an innovative way of using brine shrimp instead of goldfish to measure the effects of anesthetics. He got a paper published in Science as a result. And he caught Pauling's eye.
Robinson went on to do his Ph.D. work at the University of California at San Diego (UCSD) under the direction of physicist Martin Kamen, who remembered Robinson as the brightest graduate student he had ever had—so bright that UCSD hired him as an assistant professor right out of graduate school. It was here that he and Pauling crossed paths again, when Pauling arrived for his short stay in San Diego in the late 1960s. They began talking at UCSD about orthomolecular medicine and schizophrenia and about the reasons Pauling's earlier attempts to find a biochemical key to mental diseases by screening blood and urine had failed. They made an odd pair, the two of them, the old theorist and the young experimentalist. Politically they were polar opposites, Robinson from conservative Houston, Texas, a self defined "libertarian/conservative." But science overwhelmed any differences. Robinson thought he knew how to fix the problems with Pauling's schizophrenia project, using newer methods that coupled gas chromatography, an exquisitely sensitive way of separating and measuring the chemical components in a complex biological mix like urine, to computers that could store and compare massive amounts of data from hundreds of individuals. Pleased with the chance to work with Pauling and interested in the experimental challenge, Robinson shifted his research to match Pauling's. The two of them became close at San Diego, and Robinson soon was spending most of his time perfecting ways to pinpoint the biochemical changes associated with various diseases. Pauling and Robinson got funds for a urinalysis project on schizophrenia from the National Institute of Mental Health. Robinson, whose own parents died at about this time, took on the Paulings as surrogate parents and was a frequent guest at the Big Sur ranch, even spending Christmas with them.
When Pauling moved to Stanford, Robinson—much to the dismay of his mentors at UCSD—followed him, taking a leave of absence and trekking north with Pauling to set up his increasingly complex urinalysis equipment. By early 1972, just as Pauling's interests were turning to vitamin C and cancer, Robinson had outgrown the small temporary laboratory Pauling had been given in Palo Alto—he was by then running sixteen gas chromatographs and various pieces of computer paraphernalia—and he and Pauling asked Stanford for more space.
The school was not inclined to provide it. For one thing, Pauling was not being a quiet, well-mannered faculty member. Although the FBI had decided finally in 1972 that Pauling was no longer a threat to national security—closing its quarter-century-long investigation of the scientist, archiving the twenty-five-hundred page file it had gathered, and concluding that there was no good evidence, after all, that he had ever been a Communist—Pauling had continued his political activism. He attacked President Nixon for everything from the bombing of Cambodia to his policy in Pakistan—then told reporters that Nixon should take more vitamin C; strongly criticized the Stanford administration for firing a faculty member who had made speeches calling for an end to the university's involvement with military research; and exhorted Stanford students repeatedly to take a stand against the war in Vietnam.
That was bad enough, but by 1972, Pauling had added this apparently nonsensical obsession with vitamin C. He and Robinson were doing vitamin-loading tests on schizophrenics, giving them large doses of vitamin C, then tracking its presence in their urine (the idea was that a deficiency of ascorbic acid in the body would lead to higher uptake, thus reduced excretion), and Pauling had been pestering people at the medical school for months with requests to help him test the effects of vitamin C on patients. The continued anti-Pauling broadsides from the medical community were beginning to become embarrassing for Stanford.
When Pauling, stymied in his request for a move to larger quarters, suggesting building a modest structure for his and Robinson's work, to be funded in part by the university, in part with money he would raise himself, the administration hesitated, then reminded Pauling that he was already past the usual retirement age for Stanford professors. Finally, at the end of 1972, they said a new building was out of the question.
Art Robinson came up with the idea for a solution. He and Pauling had already arranged to get their part of the money for the proposed Stanford building, fifty thousand dollars, from Keene Dimick, the retired head of a gas chromatography company and an enthusiastic believer in Pauling's vitamin ideas. Why not tell Stanford to go to hell and use Dimick's money to rent laboratory space off campus? This was a chance, Robinson and Pauling decided, to get out of academia entirely and set up their own research institute.
The two of them talked it over with Dimick and on May 15, 1973, announced that their work would henceforth be carried out at a new research facility in Menlo Park, a few miles from Stanford. They called it the Institute of Orthomolecular Medicine.
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Pauling was now seventy-two years old, but he threw himself into the new venture with the energy of a young man. Within a few months, he had resigned his position at Stanford, Robinson severed his last ties with UCSD, and both men began looking for money. Pauling first lobbied his friends and colleagues to join the institute's board of associates—a position that meant little more than that their names appeared on the letterhead but which would lend an air of prestige to fundraising efforts—and thirty of them obliged, including Francis Crick, Maurice Wilkins, and a number of other Nobelists.
Dimick's initial stake had secured the new institute a building, but Pauling and Robinson, with only their old National Institutes of Health (NIH) urinalysis grants to fall back on, had to use their own money in part to staff and equip it. The two main areas of research were to be Robinson's urinalysis project and new proposals from Pauling for research into vitamin C. Robinson did not have much trouble getting more grant support for his side, but Pauling's attempts were less successful.
Typical was his trip to the National Cancer Institute (NCI) in March 1973. Pauling and Ava Helen arrived in Bethesda carrying Cameron's case histories of the first forty cancer patients he had treated in Scotland, which they presented to a dozen NCI officials. Pauling suggested that perhaps
it was time for controlled trials to be carried out in the United States, but the officials, after a two-hour discussion, said they could do nothing until animal tests had indicated that the treatment was both safe and effective. Once again, Pauling thought, the physicians were treating vitamin C like a drug rather than a food, but he was willing to go through the steps. He quickly applied for a $100,000 grant to carry out animal studies at the new institute. The proposal was scored too low by NCI reviewers to receive funding.
Pauling tried to correct the shortcomings noted by the reviewers and applied again in 1974. He was turned down. He applied again in 1975 and then in 1976. He was turned down each time.
Cameron himself visited NCI later in 1973, during a trip on which he met Pauling for the first time. But the two of them together could accomplish little more than Pauling had alone. The attitude of the NCI researchers seemed to be similar to that of other physicians: A few anecdotal observations at a little Scottish hospital were not enough to warrant large-scale research support. Cameron's own feelings about the National Cancer Institute were expressed in a letter to Pauling. After viewing the "really distressing" way that chemotherapy, radiation, and surgery were used in Bethesda, he wrote, "I do not know what kinds of results they are achieving, but they are certainly causing much mutilation and human suffering along the way."
In the summer of 1973, Pauling suffered another setback when a task force of the American Psychiatric Association (APA) released a long report that tore into the concept of orthomolecular psychiatry, especially Hoffer and Osmond's ideas, saying their theoretical basis was "found wanting," their experimental results were too individualized and short-term to provide good data, and their use of publicity was "deplorable." In a spirited defense Pauling wrote for the APA journal, he charged that the membership of the task force was skewed and that the report had ignored some important studies: "Neither the general theory of orthomolecular psychiatry, as presented in my 1968 paper, nor any of the special arguments about the value of ascorbic acid is presented or discussed in any significant way," he wrote; the report's conclusions, he said, were "unjustified." But by the time his article saw print the next year, the damage had been done. Again the medical establishment had spoken; again it had ruled that Pauling's orthomolecular ideas were ill-founded.
