MALARIA AND GENETICS PUZZLING SURVIVAL OF A HEREDITARY TAINT

Press, Volume XCI, Issue 27680, 9 June 1955, Page 12

MALARIA AND GENETICS PUZZLING SURVIVAL OF A HEREDITARY TAINT

[By the Scientific Correspondent of the “Manchester Guardian") (Reprinted by Arrangement)

For many years doctors and geneticists have been puzzled by the persistence among certain African populations of a hereditary taint called the “sickle-cell trait.” Evidence is now accumulating that the trait, which is responsible for the death of many infants in Africa, also confers on those persons who carry it a certain immunity from malaria. By a strange, paradox a hereditary characteristic which is itself dangerous seems essential for the preservation of population in which it occurs. Because it is one of the few simple and easily recognisable hereditary characteristics, the sickle-cell trait has been studied by human geneticists for some time, and there is now a fairly complete understanding of the way it is passed on to future generations. The nature of a person’s haemoglobin (the red content of blood cells) is determined by the nature of a pair of genes in his hereditary constitution. A man (or a woman) with the sicklecell trait has one normal and one abnormal gene in this pair, while one without the trait has two normal genes. If a man with the trait marries a woman in the same case their children may well inherit a pair of abnormal genes (on the average this will be true of a quarter of the children). And these children are almost certain to die in infancy of a characteristic form of chronic haemolytic anaemia —it seems that their haemoglobin crystallises out and becomes unable to carry out its normal task of supplying oxygen to the tissues. High Incidence Though the parents themselves are normal, it is clear that only threequarters of the children of two tainted persons will survive childhood and for this reason it would be expected that the sickle - cell traited part of a population would grow more slowly (or decrease more quickly) than the normal one. Yet in some isolated parts of Africa the trait occurs in nearly 40 per cent, of the population, while an incidence of 20 per cent, or more is fairly common in Equatorial Africa. And there is no evidence that the trait is dying out. These facts cannot be explained by assuming that the abnormal genes that characterise the trait are being produced by genetic mutation (natural or otherwise), because the rate of mutation necessary to account for them would have to be impossibly large. The only other explanation is that for some reason persons with the sickle-cell trait are able to produce more children than other members of the population, and this in turn implies' that they live longer than normal persons do. For this reason much attention has been devoted to a search for a disease which was less likely to kill tainted persons than normal ones. Since malaria is one of the most

dangerous diseases in the parts of Africa in which the sickle-cell trait is most common, it was not surprising that that disease should have been considered for this stange part. And at the beginning of last year Dr. C. A. Allison reported on a comparative study he had made of the occurrence of malaria among normal and tainted Africans. He claimed that there was evidence that normal persons were more susceptible to certain types of malaria than tainted persons. Two Investigations There has been some argument about the validity.of this conclusion; and this is not surprising, for the problem if both statistically and medically a very complicated one. But the argument has had the virtue of stimulating iurther study of the problem. And now, in the current issue of the ‘British Medical Journal” are reported the results of two separate investigations of the effect of malaria on negroes with the sickle-cell trait. One of these has been carried out at Kampala in Uganda, and it is claimed that the effect of a particular malaria parasite (the one called falciparum) on children was not so much to give them immunity from the infection but rather to limit the duration and severity of the disease. Altogether more, than 2000 children were studied. The other study was carried out by three American doctors on 16 negro volunteers who were prisoners in the Illinois State Penitentiary. They were artificially infected with malaria, and the detailed growth of the malaria parasite in their blood was studied. Though the significance of the observations was less than that of the first because of the smaller number of persons involved, there was a suggestion that the development of the disease was less rapid and its severity decreased in those prisoners with the sickle-cell trait.

Disappearing Advantage No doubt there is still a great deal of work to be done before the exact relationship between the sickle-cell trait and the different kinds of malaria is thoroughly understood. But taking all the evidence togther, it would seem that sickle cells do confer an advantage on their carriers that is sufficient to outdo some of the disadvantages to their children.

This question is likely to become of some significance in the next few years when the various campaigns in Africa against malaria (directed towards mosquitoes) are successful. For then the relative advantage of persons with sickle-cell trait will disappear and it is to be anticipated that their proportion in the African populations will decrease until it vanishes altogether. Thi» has already happened to some extent among the negro population of the United States, where the proportion of tainted persons is much less than it is in the parts of Africa from which they came (though this comparison is made difficult by the large variation in the incidence of the trait from place to place). L