The scientific research Pauling conducted during the 1930s and early 1940s gave him a unique knowledge of structural chemistry, physical chemistry, immunology, and biology as well as an experimental understanding of hemoglobin and its derivatives (oxyhemoglobin and carbonmonoxyhemoglobin). Pauling's diverse scientific background allowed him to contribute significantly to the understanding of why the red blood cells in people suffering from sickle cell anemia distort into a crescent-shape. His theory of the sickling process of hemoglobin led him to define sickle cell anemia as a molecular disease. This innovative concept of molecular disease inspired others to analyze the molecular composition of human hemoglobin.

When Pauling learned of sickle cell anemia in 1945, he drew on his knowledge gathered from his previous researches on hemoglobin and immunology and immediately thought that he comprehended the sickling process. Pauling later reflected that the idea had occurred to him in "2 seconds."