Sickle cell anemia 35 years ago: reminiscence of early African studies.

The author was a biochemist who, because he had experience in plasma iron estimations, became involved in the investigation of a hypochromic anemia in India during World War II. This led to another such study in Uganda after the war. There, an investigation of the incidence of sickling led to the discovery of overall differences between Hamitic-speaking tribes and the Bantu and Nilotes. A few exceptions could later be explained on the basis of the effect of malaria on sickling incidence. A mapping of the world distribution of sickle-cell and other hemoglobins followed, as well as a search for factors which cause the severity of sickle-cell anemia to vary. A most important lowering influence on this severity seems to be that of alpha-thalassemia. It is suggested that the high incidence of alpha-thalassemia type 2 (alpha/alpha alpha) in malarial regions is not related to malaria itself but to the beta-chain abnormalities which protect against malaria and therefore are frequent in the same populations. Alpha thalassemia in turn has a selective value because it lowers the pathological effect of sickle-cell anemia, as well as the consequences of Hemoglobin E and beta-thalassemia.