revised April 10, 2002

A Brief History of Sickle Cell Disease

Sickle Cell Disease in African Tradition

 Sickle cell disease has been known to the peoples of Africa for hundreds of years. In West Africa various ethnic groups gave the condtion different names:
Ga tribe: chwechweechwe
Faute tribe: nwiiwii
Ewe tribe: nuidudui
Twi tribe: ahotutuo

Sickle Cell Disease in the Western Literature

Description of Sickle Cell Disease
In the western literature, the first description of sickle cell disease was by a Chicago physician, James B. Herrick, who noted in 1910 that a patient of his from the West Indies had an anemia characterized by unusual red cells that were "sickle shaped.".
Relationship of Red Cell Sickling to Oxygen
In 1927, Hahn and Gillespie showed that sickling of the red cells was related to low oxygen.
Deoxygenation and Hemoglobin
In 1940, Sherman (a student at Johns Hopkins Medical School) noted a birefingence of deoxygenated red cells, suggesting that low oxygen altered the structure of the hemoglobin in the molecule.
Protective Role of Fetal Hemoglobin in Sickle Cell Disease
Janet Watson, a pediatric hematolist in New York, suggested in 1948 that the paucity of sickle cells in the peripheral blood of newborns was due to the presence of fetal hemoglobin in the red cells, which consequently did not have the abnormal sickle hemoglobin seen in adults.
Abnormal Hemoglobin in Sickle Cell Disease
Using the new technique of protein electrophoresis, Linus Pauling and Harvey Itano showed in 1948 that the hemoglobin from patients with sickle cell disease is different than that of normals. This made sickle cell disease the first disorder in which an abnormality in a protein was known to be at fault.
Amino Acid Substitution in Sickle Hemoglobin
In 1956, Vernon Ingram, then at the MRC in England, and J.A. Hunt sequenced sickle hemoglobin and showed that a glutamic acid at position 6 was replaced by a valine in sickle cell disease. Using the known information about amino acids and the codons that coded for them, he was able to predict the mutation in sickle cell disease. This made sickle cell disease the first genetic disorder whose molecular basis was known.
Cure of Sickle Cell Disease
In 1984, bone marrow transplantion in a child with sickle cell disease produced the first reported cure of the disease. The transplantation was done to treat acute leukemia. The child's sickle cell disease was cured as a side-event. The procedure nonetheless set the precedence for later transplantion efforts directed specifically at sickle cell disease.
Preventive Treatment for Sickle Cell Disease
Hydroxyurea became the first (and only) drug proven to prevent complications of sickle cell disease in the Multicenter Study of Hydroxyurea in Sickle Cell Anemia which was completed in 1995.
For more information, see "Hemoglobin: molecular, genetic, and clinical aspects", Bunn and Forget, Saunders, 1986.