Vitamin C Mutants

If high amounts of vitamin C are so important for health, why don't humans make it themselves? Most animals do, synthesizing their vitamin C internally through a series of enzyme-mediated biochemical reactions. Of all the animals on earth, only a very few—guinea pigs, a fruit-eating bat, a few bird species, and primates, including humans— do not.

The American biochemist Irwin Stone and Linus Pauling believed that humans' inability to make their own vitamin C helped explain not only why they need it in their diet but also why they need so much of it. Twenty-five million years ago, Pauling theorized, a primate ancestor lived in an area where the local fruits and vegetables were particularly rich in vitamin C. In this environment, a mutation eliminating the ability to make vitamin C, perhaps through the loss of a needed enzyme, would not be fatal. There would be enough vitamin C in the diet to make up for it.

In fact, losing the enzyme might actually be advantageous. "These mutant animals would, in the environment that provided an ample supply of ascorbic acid [another name for vitamin C] have an advantage over the ascorbic-acid-producing animals, in that they had been relieved of the burden of constructing and operating the machinery for producing ascorbic acid," Pauling wrote. Freeing the energy formerly needed for making vitamin C would allow the mutant animals to devote that energy to other needs. They would therefore be able to compete more efficiently and would flourish.

In Pauling's view, the system worked well as long as the local diet provided the necessary high levels of vitamin C. But as these primates moved out of their tropical valley, their health began to suffer as their vitamin C intake went down. Their dietary intake of vitamin C was no longer enough to replenish the "natural" levels their bodies had once produced internally.

That, Pauling felt, was why we now needed to supplement our diets with extra doses of vitamin C. It was because we are vitamin C mutants, still trying to regain the health we once enjoyed in that long-ago vitamin C—rich Eden.

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minimal amounts of a needed molecule might improve health. After doing a little reading on his own and discovering that high doses of vitamin C seemed to pose no significant health dangers, Pauling decided to give it a try. He and Ava Helen both began taking 3,000 mg per day.

The results were astonishing. They each found they had greater energy, an increased sense of well-being, and, best of all, that they seemed to be able to fight off the particularly nasty colds Pauling had long been prone to.

For three years, Pauling kept his ideas about vitamin C and health to himself as he left the CSDI and set about finding a place where he could redevote himself to science. He spent the 1967—68 academic year as a visiting professor at the University of California at San Diego, a position that not only allowed him to teach again but provided him limited laboratory space where he began a series of biochemical experiments with a young, brilliant, hard-working researcher named Art Robinson. The position looked at first as if it might evolve into a permanent one, but a combination of Pauling's age (he was now 67, the standard retirement age for UC professors) and his still-outspoken views on peace (he was now protesting the Vietnam war and sometimes urged students to go on strike to protest American militarism) convinced the university regents to limit their offer to an additional one-year term. Despite his stature as the world's only two-time solo Nobelist, it appeared to them that Pauling was too old and too much trouble to have around.

So he and Ava Helen moved again, this time to Stanford University, where he was able to arrange a position as a consulting professor of chemistry only by agreeing to use his book royalties and investment income to pay half his own salary and all his expenses. Stanford was a great improvement over San Diego, in several ways. For one, the Stanford chemistry faculty and school administrators seemed happy to have Pauling there. For another, there

■ Linus Pauling were no problems at this private university with state-mandated retirement ages. And, finally, the location of the school, south of San Francisco in the pleasant, tree-filled small city of Palo Alto, was much closer to a second home the Paulings had built with his Peace Prize money on the spectacular Big Sur coast. Working at Stanford, they could easily travel to Big Sur on weekends and in the summers. After all their wandering, Linus and Ava Helen Pauling settled into the Stanford area for what they hoped would be a very long time.

Art Robinson followed Pauling to Stanford, where he assisted Pauling with new research into the orthomolecular basis of health. Robinson was expert in using gas chromatography, an exquisitely sensitive method of separating and analyzing the chemical components in complex mix-

An excerpt from a speech Pauling gave in Los Angeles in 1968 attacking U.S. policy in Vietnam.

OvJL A^jte^ oA^ Hp j tures such as urine and blood, which he combined with computer analysis and used as a tool to track the fate of molecules in the body. Together, Pauling the old theorist and Robinson the young experimentalist were determined to test Pauling's orthomolecular ideas.

Their work went quietly until late 1969, when Pauling, delivering a lecture, noted in passing his success in using vitamin C to prevent colds. Local newspapers spread the story, and soon Pauling's claim that high doses of vitamin C were good for a range of ills became public. In response, several physicians attacked his assertions. Where, they demanded, were the scientific studies needed to prove his ideas?

Pauling began gathering them. He found five well-run, large-scale medical studies that he believed indicated strongly that higher-than-normal doses of vitamin C could reduce the incidence and severity of colds. Some of the studies had provided their subjects with just a little extra vitamin C, and found a small effect. Others had given higher doses and found a greater effect. The largest doses were given in a Swiss study of skiers, where half of a large group got 1,000 mg of extra vitamin C per day and the other half none. The vitamin C group had 61 percent fewer days of upper respiratory illness and a 65 percent decrease in the severity of their colds. It was clear to Pauling that the more vitamin C you took, the healthier you were. This little research exercise convinced Pauling that he was onto something very important. By taking more vitamin C—a cheap, safe nutrient—millions of people could improve their health. The sum of human suffering would decrease. And all this could happen without resorting to expensive physicians or dangerous drugs. Pauling began excitedly writing up his findings for both a scientific journal article and a book for the general public.

It was the beginning of the greatest scientific and public relations roller-coaster ride of Pauling's life. His scientific paper was rejected by Science, but his popular book, Vitamin C and the Common Cold, published in the fall of 1970, became a best-seller. Pauling promoted his book in newspapers, magazines, radio interviews, and on television. People began buying vitamin C in quantity. Sales double, tripled, and quadrupled over the course of a few months. Drugstores sold out. Manufacturers began building new factories to keep up with the demand. The vitamin industry had never seen anything like it.

But most physicians remained skeptical. The head of the U.S. Food and Drug Administration called the run on vitamin C "ridiculous," saying, "there is no scientific evidence and never have been any meaningful studies indicating that vitamin C is capable of preventing or curing colds." The Journal of the American Medical Association said 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 was criticized in the medical press for going directly to the public without first printing his ideas in scientific journals, where submissions were judged by experts before publication; for hand-selecting a few studies that favored his views; and for advocating a significant change in diet without any knowledge of the long-term health effects.

Just as he had done in the nuclear weapons debate, Pauling responded to his critics by fighting harder. He had never argued, he said, that vitamin C could cure colds. He understood that humans varied both in their reaction to vitamin C and to colds: Some never got colds whether they took vitamin C or not; others would get colds regardless of how much they took. But for the vast majority, Pauling believed, vitamin C could strengthen the body, increase resistance, prevent some colds, and lessen the effects of others. He then challenged his critics to bring forward one case where a few grams a day of pure vitamin C had harmed anyone (beyond an occasional bout of diarrhea or a stomach upset, they could not). And he continued finding more medical studies to back up his views.

He also pointed out that he had tried to go through the scientific press and been turned down. But being turned down did not deter him. He believed the public had a right to know about this chance to improve their health, so he had gone directly to them. As for his critics in the medical press, didn't the medical press make quite a bit of money off of cold remedy advertisers?

People began taking sides in the great vitamin C debate. On one side were most physicians, some nutritionists, and a few other scientists who said Pauling was an old Nobelist who was far out of his field, a nutritional quack, a health faddist, a kook. On the other were a few scientists who knew Pauling well enough to treat his insights with respect—and 50 million people who, by the mid-1970s, were all taking extra daily doses of vitamin C.

The administrators of Stanford University were not happy to see one of their faculty members being called a quack. Nor were they pleased with Pauling's repeated calls to students to protest the Vietnam War. It was thus not a great surprise when, in the early 1970s, they turned down Pauling and Robinson's request for more room to conduct vitamin C studies.

Robinson came up with a solution. He knew a wealthy manufacturer of gas chromatography equipment who would provide them money for laboratory space off campus. Why not quit Stanford and start their own research institute? They could have their own scientific home, raise their own money, and be their own bosses.

Pauling agreed to give it a try. In the spring of 1973 an arrangement was made for funding, and he and Robinson announced that they were going to open the new Institute of Orthomolecular Medicine a few miles away from Stanford.

Now 72 years old, Pauling threw himself into the new venture with the energy of a young man. While Robinson set up the complicated laboratory equipment and oversaw the day-to-day management of the institute, Pauling began traveling, speaking, and writing grant requests to raise the money needed to fund new research projects into the health benefits of vitamin C. The more he learned, the more convinced he became that increased vitamin C was beneficial not only for colds, but for preventing the flu, for extending the average lifespan—even for treating cancer.

But he had a difficult time convincing any granting agency to help him prove his ideas. The National Cancer Institute turned down his grant requests, saying that the existing evidence was too sketchy and Pauling's institute too small to support major studies. Unable to raise money from the usual sources, Pauling turned to the public. The power of his name had convinced millions of Americans to take extra vitamin C, and now the power of his name was added to appeals to the public to help support his institute, which was renamed The Linus Pauling Institute of Science and Medicine. A professional fundraiser was hired and a huge campaign of advertisements and direct mail requests for contributions begun.

The public responded. Hundreds of thousands of dollars began to flow into the institute in the mid-1970s. Robinson began dreaming of relocating to Oregon, building a brand-new institute and expanding to become an internationally respected research center.

This dream was not shared by others at the institute. Many of the researchers and employees liked it in California and did not want to move. And some were unhappy as well with Robinson's sometimes authoritarian management style. Instead of making great research possible, the money broke the Pauling institute into warring camps.

Robinson was on one side, Pauling the other. Robinson had given up his career at San Diego to follow Pauling and

Linus and Ava Helen a few months before her death in 1981

Linus Pauling Death

was now staking his entire future on the institute. While Pauling continued traveling widely to speak on peace issues and spent a good deal of his time secluded at his Big Sur ranch, Robinson spent every minute keeping the place going. He had his own ideas about vitamin C as well, and began redirecting experiments to fit those theories. "Art had gotten into the habit of thinking of the institute as his institute," Pauling later said.

But it was not Robinson's institute—it was Pauling's. And when Pauling heard about the staff dissatisfaction, and at the same time learned that Robinson had begun turning the vitamin C research into areas that he had not agreed to, he decided enough was enough. In June 1978, he asked Robinson to resign. Robinson refused to do that. Instead, outraged at the way he had been treated, he sued Linus Pauling and the institute for $25.5 million.

This was enough bad news, but there was worse to come. Ava Helen fell ill, and the diagnosis was bad: cancer of the stomach. The resulting surgery weakened her tremendously. She seemed to age 10 years in a few months.

Linus and Ava Helen a few months before her death in 1981

But despite her physician s recommendation, she would not take chemotherapy. Instead, she increased her intake of vitamin C to 10,000 mg per day.

For a while, it seemed to work. She regained her energy and strength, and felt well enough to accompany Pauling on his many speaking trips. She took up music, learning to play folk songs on the guitar and buying a grand piano for their Big Sur home. She and Pauling were inseparable during those times in the late 1970s. They were good days, full of love and music, visits from her children and grandchildren and, best of all, the weeks when Linus and she were alone, just the two of them, old lovers listening to the sea.

In 1981, however, the cancer came back. This time no amount of vitamin C could help her, although Pauling kept trying. He still held on to the hope that massive doses would perform a miracle, as it had with some patients with advanced cancer that had been reported in Scotland, that somehow he could make her cancer disappear. He worked ceaselessly to save her.

But this was one battle he could not win. Ava Helen died at home on December 7, 1981.

The first few months after her death were the hardest. Pauling found himself moaning uncontrollably and wept whenever her name was mentioned. He would never fully stop grieving. Slowly, however, he learned how to get on with his life alone.

Because of Pauling's urging, the National Cancer Institute had decided to fund a pair of studies at the internationally respected Mayo Clinic in Minnesota to see if vitamin C really could help cancer patients. Pauling had eagerly awaited the results but was deeply disappointed when they were published. Both studies of terminal cancer patients appeared to show that the vitamin had no effect in prolonging life. The medical community took this as the final word on the subject, although Pauling spent months trying to convince them the studies were flawed.

In 1986, he published a book of health advice titled How to Live Longer and Feel Better, which distilled everything he had learned about vitamins, minerals, and diet. The cover was graced with a picture of Pauling in his mid-80s, still vibrant, ruddy, bright-eyed, and evidently glowing with good health, a walking advertisement for vitamin C. The book was another best-seller.

Even in his mid-80s, and without Ava Helen, Pauling continued to travel extensively, speak widely, and publish regularly on topics from crystal structure to nuclear physics, superconductivity to human metabolism, chemical bonding to world peace. He never stopped receiving awards and honorary doctorates, or advocating vitamin C.

Then, slowly, much more so than he had once hoped, scientific opinion began shifting his way. A new group of younger researchers began looking at vitamin C from a new angle, studying its abilities as an antioxidant, a substance that stops destructive bits of molecular debris called free radicals from damaging cells. In 1990, the National Cancer Institute, impressed by the growing body of evidence, sponsored an international conference on vitamin C. There were presentations on the vitamin's importance in metabolic reactions, its effect in delaying tumor onset and growth, and its ability to prolong survival times, reduce treatment toxicity, and increase the efficacy of other treatments. "It was great! A great affair!" Pauling said when it was over.

And the evidence kept mounting. A medical newsletter pointed to the fact that vitamin C had been shown to have a protective effect against various cancers in 34 of 47 studies examined. Time magazine ran a cover story about amazing benefits apparently attributable to taking extra vitamins, especially antioxidants such as vitamin C. An epidemiological study showed that men who took an extra 500 mg of C per day could expect to live an average of five years longer than men who did not. In 1992, at the end of a special meeting of the New York Academy of Sciences devoted to

■ Linus Pauling

Linus Pauling in the study of his Big Sur home in 1987 He spent his final years overseeing health research at his institute and trying to describe the structure of atomic nuclei.

Linus Pauling in the study of his Big Sur home in 1987 He spent his final years overseeing health research at his institute and trying to describe the structure of atomic nuclei.

studies of high-dose vitamins and other nutrients, a nutrition professor rose and said, "For three days I have been listening to talks about the value of large intakes of vitamin C and other natural substances, and I have not heard a single mention of the name Linus Pauling. Has not the time come when we should admit that Linus Pauling was right all along?" The response was a prolonged round of enthusiastic applause.

Pauling, now in his 90s, was pleased by the good news, but he no longer cared as much as he once might have. He himself had been diagnosed with cancer. He underwent a series of surgeries in the winter of 1991—92, then began treating himself with high doses of vitamin C, raw fruits and vegetables, and an experimental technique to boost his immune system.

He spent most of his time at the Big Sur ranch, perched on the edge of a bluff over the Pacific, making calculations, entertaining old friends who came to visit, looking out to sea. His children took turns taking care of him. He completed a final set of papers on the structure of atomic nuclei, a subject that had interested him since his early student days at Caltech. Then he laid down his pen.

Linus Pauling died at Big Sur on August 19, 1994.

I Linus Pauling

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