Why was sickle-cell anemia called the first molecular disease?

Sickle-cell anemia is recognized as the first "molecular disease" because it was the first disorder identified as being caused by a specific structural alteration in a protein resulting from a genetic mutation.12

In 1949, American scientist Linus Pauling and his colleagues demonstrated that hemoglobin extracted from the red blood cells of individuals with sickle-cell anemia behaved differently than hemoglobin from healthy individuals. Pauling hypothesized that the characteristic "sickling" of the red blood cells was caused by a genetic mutation affecting the globin portion of the hemoglobin molecule.12

By identifying this specific molecular defect, Pauling provided evidence that mutant genes could direct the formation of abnormal proteins with altered functions, thereby establishing the fundamental link between genetics and molecular structure in the study of disease.12