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In the mid-1950s, with his research on mental disease, Pauling began to form a comprehensive theory of human health. Thanks to the Ford Foundation grant, he immersed himself in the fields of psychiatry and general health, always on the lookout for another molecular disease that might lend itself to new therapy. By the mid-1960s he was coalescing his findings into overarching theory, combining much of what he knew about chemistry and health. He called his new idea "orthomolecular" medicine.
Pauling's approach was based on a belief that the body could be seen as a vast laboratory full of chemical reactions: among the most important were enzyme-substrate reactions, energy-producing reactions, antibody-antigen reactions, the chemical interactions that resulted in cellular reproduction and genetic duplication, and electrochemical reactions in the brain and nerves. Health, in this view, resulted when all was well run and reactions were moving ahead properly; disease resulted if the proper reactions were hindered or stopped. Optimal health could be achieved by perfecting reaction conditions and making sure that the body maintained the proper balance of chemicals--nutrients, catalysts, and products. After thinking about this balance for years, he coined a term to describe it: orthomolecular, meaning "the right molecules in the right amounts."
He first used the term in print in 1967 in relation to psychiatric therapy. He had by then become convinced that conditions such as schizophrenia could be treated with nutrients such as niacin, an approach developed by Abram Hoffer and Humphrey Osmond. However, his theory of orthomolecular psychiatry was ignored or criticized by the medical community.
Undeterred, Pauling expanded his orthomolecular concept to other areas. But his ideas were outstripping the technology of the time. In order to prove his ideas, he needed to track the activity of very small amounts of nutrients in very complicated biological systems. To do so, he needed more sophisticated analytical tools than had yet been invented. He spent years, for instance, working with other researchers to combine gas chromatographic equipment with computers for urinalysis. Definitive results were few.
At the end of the 1960s, Pauling participated in an exchange of correspondence with Irwin Stone, a biochemist who had attended one of Pauling's lectures. Stone wrote to him recommending that he take increased amounts of vitamin C, which the biochemist believed would boost his health and extend his life. Pauling began to familiarize himself with the subject. In reviewing the literature, he saw that there was some evidence in favor of large doses and began taking more of the vitamin. He immediately felt better and suffered fewer colds, and by 1969 he was commenting to reporters that physicians should pay more attention to vitamin C. In response Dr. Victor Herbert, a clinical nutritionist who had helped set the FDA's recommended daily allowances for vitamins, wrote Pauling a letter demanding the evidence for recommending increased doses of vitamin C.
Pauling responded by reviewing the scientific literature on the health effects of supplemental vitamin C. The result was a book published in 1971, Vitamin C and the Common Cold, marshaling the research data. It became a sensation, kicked off a public controversy in the press, and helped convince millions of people to take more vitamin C. The medical community roundly attacked both the findings and Pauling's credibility. Typically, Pauling fought back. In 1973, he co-founded (with Arthur Robinson, a young colleague who had worked with him on the urinalysis project) the Institute of Orthomolecular Medicine in Palo Alto, California, to pursue his ideas.
In the view of the medical community, Pauling's promotion of large doses of vitamins for everything from the common cold to cancer has often gone beyond the available evidence. However, in more recent years, re-evaluations of Pauling's work have shown that dietary supplementation with antioxidants such as vitamin C can have significant beneficial effects on health. Pauling's ideas about molecular balance and health are increasingly important to a health-conscious public, as well as to a growing number of health professionals.