Linus Pauling (1901-1994)

The name, Linus Pauling, is often identified with vitamin C, the common cold and flu, and the treatment of cancer. Yet while it is true that Linus Pauling, PhD, did more to advance awareness of the role of vitamin supplementation in health promotion than any person in history, to narrowly define his contributions to vitamin C advocacy is to overlook the scope and impact of Dr Pauling’s work, which spanned more than 70 years.

Many biographies have been written about the life of Linus Pauling and his wife Ava Helen. One of my favorites is Force of Nature: The Life of Linus Pauling by Thomas Hager.¹ This book offers an excellent historical account of their lives, and reveals the impact they had and still have on society.

However, given that you can read about his life in many sources, my comments in this history will focus on a few of the personal experiences I had with Linus and Ava Helen Pauling, both before and during my time as a research associate at the Linus Pauling Institute of Science and Medicine. These personal experiences, I believe, offer insight into the legacy left behind by their work and advocacies.

One afternoon, during a meeting with Dr Pauling, I was struck by a framed photograph on the wall of his office. The photograph—a snapshot of Dr Pauling, Albert Schweitzer, and Albert Einstein—depicted the three men collaborating around a small wooden table. Dr Pauling explained that Ava Helen had captured the image during a meeting in Schweitzer’s compound in Africa where the three of them were developing plans to convince 30 000 international scientists to sign a petition against the atmospheric testing of nuclear weapons.

The photograph was symbolic of the scope of Linus and Ava’s advocacy and of the impact that the couple had on the world community. Linus and Ava Helen had also been involved in the organization and implementation of worldwide immunization against smallpox. Although it was an unpopular position, Dr Pauling had advocated free exchange of scientific information among scientists of all countries—regardless of their political affiliation—in an effort to reduce illness and suffering around the world.

Why did Dr Pauling advance these concepts at such personal peril? He had made a promise to his wife, he explained to me. His promise—to be more actively involved in communicating the societal implications of the work in science—arose from Ava Helen’s avowal: “if scientists will not speak up for what they feel is right, when they know the answers, then who will?” Dr Pauling followed through with this sociological commitment for the rest of his life. In every one of his presentations, no matter how scientific, he interjected an element of social consciousness into the discussion.

In another discussion between us, I asked which, among the thousands of publications that he had amassed during his lifetime, was he most proud? Dr Pauling immediately went to his desk and uncovered a reprint of his article “The Nature of the Chemical Bond,” which was published in the Journal of Chemical Physics in 1931.² This article, he professed, was of particular importance because it charted the path of a new concept, “structure/function,” or the relationship between structure of molecules and their function. The concept of “structure/function” may be applied to chemistry, biochemistry, physiology, medicine, or society in general, but it was a central theme that tied all of Linus and Ava Helen Pauling’s work together. The Pauling’s work for peace emerged from an application of “structure/function.” According to their concept, when relationships among people are not “forced,” but rather allowed to find the correct “structure,” the correct “function” results, and peace will follow.

By a similar line of reasoning, Dr Pauling maintained that the right fit of biomolecules in physiology promotes their proper function. The landmark paper he authored in Science magazine in 1949 described the concept of “molecular medicine” for the first time.³ Dr Pauling’s paper demonstrated that even very small changes in the shape of molecules, such as the alteration of hemoglobin in sickle cell anemia, could have profound effects on their “function.”

This theme was further extended in his watershed article entitled “Orthomolecular Psychiatry” that appeared in Science in 1968.⁴ In this article, Dr Pauling proposed that many diseases, including certain forms of mental illness, were the result of the individual not having the proper balance of a certain molecule such as a vitamin in their body to promote proper function. He further went on to suggest that the level of substances needed to promote proper function was based upon an individual’s genetic uniqueness and might vary significantly from the mythical “average person.” In 2002, Bruce Ames, PhD, emeritus professor of biochemistry from the University of California at Berkeley, authored tour-de-force paper demonstrating that, for hundreds of genetically-determined diseases, the model of molecular medicine defined by Dr Pauling was correct.⁵

In the 1950s, Dr Pauling contracted a kidney infection while traveling on a train from New York to California. By the time he arrived in California, he was quite ill and sought the opinion of a leading nephrologist at the medical center of Stanford University, Dr Thomas Addis. Dr Addis suggested that Dr Pauling go on a low-protein diet supplemented with high doses of vitamin C.

While reviewing how vitamin C might influence kidney function, Dr Pauling recognized that the function of the kidney when ill might depend upon certain biochemical processes that demanded higher intakes of vitamin C. He tried Dr Addis’ suggestion and had success within two weeks.

He later met Irwin Stone, PhD, who had also developed the concept that much higher doses of vitamin C than was necessary to prevent scurvy might be required to promote proper physiological function. As Louis Pasteur was quoted as saying, “chance of making an observation falls to the prepared mind.” Indeed, Dr Pauling’s mind was more than prepared to make the observation as to how the structure of molecules could influence the function of the individual.

The evolution of “molecular medicine” beyond the 1950s paradigm progressed with a slow reception from the body politic of medicine. It was easier to criticize the aspects of molecular medicine that were not understood rather than to gain an understanding of its meaning. At first, Dr Pauling was criticized as having stepped outside his area of expertise. His concepts were discounted, and it was rumored that he was senile. In the end, however, Dr Pauling was able to note with irony that, “over time, the physicians my age who were critical to my concepts all died—leaving new open minds to examine the concepts.”

His continued supplementation with 6 000 mgs or more of vitamin C daily was considered by many to be silly and possibly dangerous. Nevertheless, in 1991, at the age of 90, Dr Pauling authored five papers that were considered important contributions to the development of structural chemistry.

On Friday, August 19, 1994, at 93 years of age, the world lost a priceless asset with the passing of Dr Pauling. Nearly a decade after his death—more than seventy years after he introduced structure/function— we are witnessing the dawn of the age of medicine based upon the understanding of biological systems introduced by Dr Pauling. In 2003, with the increasing understanding of the role that nutrients play in genetic expression and metabolomic control, the Pauling “hypothesis” is being confirmed. The evidence that genetic differences in the manner that the levels of folic acid, pyridoxine, cobalamine, riboflavin, and trimethylglycine influence physiological function in a way that translates into disorders as diverse as spina bifida, Down Syndrome, coronary heart disease, cerebrovascular disease, cancer of the colon and breast, dementia, and depression illustrate Dr Pauling’s concept of structure/function. This evidence enables us to observe how the structure and function of various nutrients can influence the structure and function of the body.

Dr Pauling taught us that health is more than the absence of disease. He argued that molecules from nature influence our function in ways that often differ from those molecules that have been derived from chemical synthesis.

In the future, biochemistry and functional genomics courses will be seen as having exciting applications that will improve the patient-outcomes through the application of personalized medicine, rather than as a required course to survive in medical school.

We owe Linus and Ava Helen Pauling much for their pioneering discoveries and advocacy in helping us to see on many levels the importance of “structure/function” in providing a path to the resolution of many problems associated with human suffering.