The Linus Pauling Institute, currently located on the Oregon State University campus, focuses its research on orthomolecular medicine and orthomolecular psychiatry, disciplines that Pauling defined in 1968. Pauling described orthomolecular therapies as using large doses of substances normally present in the body (e.g. vitamins), instead of introducing man-made substances (e.g. antibiotics). Orthomolecular medicine uses natural treatments for diseases, such as the treatment of diabetes with insulin. Orthomolecular psychiatry treats diseases causing mental retardation, for example, prescribing a low phenylalanine diet for phenylketonurics.

Pauling claimed that his interest in this field arose from his learning about experiments performed by Abram Hoffer and Humphry Osmond using high doses of niacin (also called nicotinic acid) to combat mental disorders. In 1965 Pauling had read Hoffer's book, Niacin Therapy for Psychiatry, which described "megavitamin therapy." Pauling's interest grew early the next year when biochemist Irwin Stone informed Pauling that he would live longer if he took large doses of vitamin C, which is also called ascorbic acid.

Zuckerkandl worked at the Linus Pauling Institute and became its president and director in 1980, a post he left in 1991. In 1985 Zuckerkandl outlined the Institute's goals by discussing the connection between molecular disease and orthomolecular medicine. Citing the scientific and medical significance of the sickle cell anemia article by Pauling, Itano, Singer, and Wells, Zuckerkandl noted that whereas some mutations in deoxyribonucleic acid (DNA) do not cause debilitating molecular diseases, others do. The Institute aimed to find remedies for sicknesses by learning more about vitamins and the human body's need for nutritional substances.