EVOLUTION, GENETICS, ANTHROPOLOGY — MOURANT 509 



anemic ones it occurs by itself. It gradually became clear that, apart 

 from cases where other abnormal genes complicate the picture, the 

 anemic persons with sickle-cells are homozygous for a gene determin- 

 ing the synthesis of the abnormal sickle-cell hemoglobin, that is to 

 say, they have received such a gene from both parents, while the 

 healthy sicklers, who have a mixture of abnormal and normal hemo- 

 globin, are heterozygous for the same gene, having received an ab- 

 normal gene from one parent and a normal one from the other. Since 

 under African conditions virtually all homozygous sicklers die without 

 producing offspring, the frequency of their abnormal gene might be 

 expected to diminish appreciably with every generation. Nevertheless 

 there are numerous tribes in Africa with total frequencies of sicklers, 

 mainly heterozygous, as high as 40 percent. It was a simple matter 

 of genetical calculation to show that, in these tribes, about 4 percent 

 of the babies conceived, and indeed of those born alive, since the 

 condition is not lethal in utero, must be homozygous sicklers, almost 

 inevitably destined to an early death. The question therefore arose 

 as to how such high frequencies of sicklers could exist, and presumably 

 persist from generation to generation. 



One suggested explanation was that mutation, or spontaneous 

 change from the normal gene responsible for producing normal hemo- 

 globin to the abnormal one causing the production of the sickle-cell 

 variety, was taking place with sufficient frequency to balance the loss 

 of abnormal genes through deaths from anemia. This, however, 

 implied a frequency of change thousands of times higher than for 

 almost any other known case of mutation, and so seemed most un- 

 likely to be the true explanation. The only alternative appeared to 

 be that the abnormal heterozygote, under African conditions, enjoyed 

 a selective advantage, not only over the abnormal homozygote, but 

 also over the normal homozygote. This is a situation well known to 

 geneticists, and is called balanced polymorphism, in which the supply 

 of both genes is replenished from the pool represented by the favored 

 heterozygote, so that the balance between them tends to remain stable 

 from one generation to another. Several workers suggested that the 

 advantage enjoyed by the heterozygotes might be that they were more 

 resistant than normal persons to malaria ; that this was so was first 

 clearly demonstrated by Allison (1954) who also showed that the 

 variety of malaria involved was the malignant tertian type. The 

 relative resistance of heterozygotes to malaria was confirmed by Eaper 

 (1956) who worked out more fully how this resistance operated. The 

 complete solution of this primarily medical problem took many years 

 to reach, and was achieved only because the clinical investigators had 

 the close collaboration of biochemists, geneticists, and anthropologists. 

 Such a situation is at the moment unique but it may become not in- 



