In the title of their 1949 paper, Pauling and his colleagues called sickle cell anemia a molecular disease because the sickled cells caused the pathology: "…if it [the mechanism for the sickling process] is correct, it supplies a direct link between the existence of 'defective' hemoglobin molecules and the pathological consequences of sickle cell disease." In other words, structure influences function. During the years following the paper, Pauling often defined molecular disease and incorporated sickle cell anemia into his discussions, which focused on molecular disease, hemoglobin, nuclear fallout, and evolutionary theories. He considered the coining of a clear definition of molecular disease to be an important, original contribution to understanding the relationship between molecules and disease.

Ultimately, Pauling believed that remedies for molecular diseases could be found once there was an understanding of the molecular structure of normal and abnormal proteins within the human body. This field of inquiry was to be molecular medicine. In 1962 Pauling noted that two newly emerged disciplines, molecular biology and molecular medicine, would aid in abating molecular diseases. "I believe that the continued study of the molecular structure of the human body and the nature of molecular disease will provide information that will contribute to the control of disease and will significantly diminish the amount of human suffering. Molecular biology and molecular medicine are new fields of science that can be greatly developed for the benefit of mankind." About five years later, Pauling coined two terms, orthomolecular medicine and orthomolecular psychiatry, to describe a specific approach to treating molecular diseases and his newest field of interest.