Sickle cell anemia was first described in 1910, after Ernest E. Irons, an intern at Chicago's Presbyterian Hospital, noticed elongated cells in a blood smear from Walter C. Noel, a dental student with severe anemia.
In the late 1940s, Pauling and his colleagues realized that sickle cell anemia stems from a change in the structure of hemoglobin. In 1956, Ingram discovered that a specific chemical alteration in a hemoglobin protein - the substitution of valine for glutamic acid in the sixth amino acid in beta globin - is the root of the disease. Other mutations in hemoglobin can also cause sickle cell anemia, and were sorted out later.
Herrick J.B. Peculiar elongated and sickle-shaped red blood corpuscles in a case of severe anemia. Arch Intern Med, 6: 517-521. 1910.
Pauling L., Itano H.A., Singer S.J., Wells I.G. Sickle-cell anemia, a molecular disease. Science, 110: 543-548. 1949. [PubMed]
Ingram V.M. Specific chemical difference between the globins of normal human and sickle-cell anemia haemoglobin. Nature, 178: 792-794. 1956. [PubMed]
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