Pauling spent the decade from 1963 to 1973 in flux. His liberal politics and scientific work on mental diseases caused him professional problems at Caltech after the mid-1950s. In response to Pauling's alleged association with communism, Caltech administrators stopped giving him pay raises, and in 1958 Pauling reluctantly agreed to resign as Chairman of the Chemistry Department. In 1963 administrators needed more work stations in the chemistry laboratories, and the new Chairman of the Chemistry Division informed Pauling that some of his laboratory space being used for research on mental diseases was needed for research in other areas.

Additionally, Pauling had been diligently pursuing peace work in the political arena since the late 1940s, and in 1963 he was awarded the 1962 Nobel Peace Prize. Caltech's overall reaction was lukewarm at best and deeply upset Pauling. Spurred by the monetary award he received with the Nobel Peace Prize, Pauling resigned from Caltech shortly thereafter.

For ten years Pauling worked at various institutions in California before deciding to start his own, eventually named the Linus Pauling Institute of Science and Medicine. Arthur Robinson helped Pauling start the Institute in 1973; Robinson had been an undergraduate at Caltech in the early 1960s and went to University of California at San Diego (UCSD) for his graduate degree and stayed there to teach. While Robinson was at UCSD, Pauling also taught there and influenced Robinson to pursue orthomolecular medicine. When Pauling left San Diego for Stanford University, Robinson followed. Robinson oversaw the daily administration of the Institute for its first five years, when it was located near Stanford University.