Sickle-cell Anaemia

By Felix Konotey-Ahulu, M.D. (Lond.), FRCP, DTMH

The following section is abstracted, with permission, from Dr. Konotey-Ahulu’s book: ‘The Sickle Cell Disease Patient”
There is no single clinical experience in the United States comparable to that of Dr. Konotey-Ahulu“.

Professor Helen Ranney MD, Albert Einstein College of Medicine, New York, in Sickle Cell Disease, Editors H. Abramson, J.F. Bertles, Doris Wethers (C. Mosby Co.) 1972 p 320.

Evolution and the sickle cell gene
“Sixth formers that this author has lectured on genetic counselling invariably pop some such question as: ‘Is it true that the sickle-cell phenomenon has established Darwinian evolution as fact?’ Behind the question lies, of course, the confusion between adaptation by mutation and Darwinian evolution which implies that more complicated forms seen today arose from simpler forms traced back ultimately to one-cell organisms. In his pre-clinical years in the early fifties the author of this book did a course on evolution and metaphysics at the feet of Professor J. Z. Young FRS, perhaps the greatest evolutionist of recent years. Nothing has happened during the past 30 years in molecular biology in general, and the sickling phenomenon vis a vis malaria in particular, to have raised evolution from theory to established fact. Though he thought the theory of evolution seemed plausible, even Crick of DNA fame thought it suffered from a major defect – being too accommodating. In a loose sort of way it can explain anything (Crick, 1968). 

A scientific theory that tackles ‘origins’ must of necessity find that it is out of its depth. In his latest book ‘The Limits of Science’, Sir Peter Medawar (1985) another Nobel Laureate states clearly that certain questions like ‘origins’ go ‘beyond the explanatory competence of science’. For people to state that because sickle cell trait children are resistant to cerebral malaria the origin and perseverance of life as we know it today become immediately explicable on Darwinian lines is more a statement of ‘faith’ than of ‘science’. Writing in The Times on ‘Scientific tests for Darwinism’ Professor Andrews of London University states: “The insistence that mutation plus natural selection (the neo-Darwinian mechanism) has, as a matter of fact, given rise to the biosphere as we know it today, has been repeated so frequently by evolutionists in textbook after textbook, that the average person must be forgiven for thinking that evolution and Darwinism are one and the same thing.’ (Andrews, 1981). He goes on to say that ‘the mere assertion that all living things evolved from a common ancestor is far too simple…’. 

The present author is convinced the proof that evolution did take place must be sought elsewhere, and not in the adaptive processes against P. falciparum, any more than that his black skin’s ability to withstand the tropical sun establishes an evolutionary process starting perhaps with a Big Bang, to unicellular organism –> multicellular organism –> invertebrates –> vertebrates –> man. In a realm where there is no lack of theories a new discipline is rapidly gaining popularity among athropologists. This is known as ‘co-evolution’ in which cultures, customs and social behaviour including tribal festivals are supposed to have co-evolved through natural selection alongside heritable characters (Durham 1976). 

Unfortunately for the theory one premise used for erecting the pillars of the theory was quite erroneous. The festivals in west Africa and the beliefs associated with them result, according to one theory, in enhanced genetic fitness of individuals who support the belief. This was arrived at because yams of the genus Dioscorea are known to contain cyanogenic glycosides which when changed in the body to cyanate was effective at reducing the rate of sickling in deoxygenated red blood cells by impeding the crystallization of Hb.S. In the yam zone, consumption would have approached 2 kilograms per adult per day according to Durham (1979); thus clinically effective ‘doses’ of thio-cyanate are routinely consumed day after day. This simply is not correct. Yam, as the ‘queen of crops’, is expensive so it is often kept in reserve. Moreover the term ‘yam festival’ is a European designation for ‘harvest festival’. Of the many tribes in the so-called Yam zone only 10% have yams featuring in their harvests (Opoku 1970; ISD 1983) so the customary pre-harvest prohibition of eating new yams for a month, on which Durham builds part of his theory occurs in only 10% of the population. He hypothesized that the beliefs behind the New Yam festivals and the New Yam prohibitions evolved culturally under the increasing influence of malaria and the frequency of the sickling gene; as the frequency of the S allele increased under malarial selection, the health benefits of a carefully timed New Yam prohibition would have become increasingly evident in local populations: Durham (1982). 

The author of this book who was born and bred in Durham’s ‘yam zone’ categorically denies any connection between yam festivals, malaria, and the sickle cell gene. Such theses and hypotheses of some anthropologists and theoretical geneticists detract from more serious work on ‘evolution’ or genetic adaptation as recorded by Kan and Dozy 1980; Kan 1982; Straus and Taylor 1981; Bowman 1983; Pagnier et al. 1984. Even Edelstein’s serious work (1986) on aspects of evolution of the sickle cell gene must be considered an oversimplification.

The fact of proliferation of genes per se should not direct attention immediately to natural selection. Genetic predisposition to stuttering, for example, is very high in west Africa but to find 5 stutterers among 10 west African sickle cell trait individuals in the UK and to be led to associate stuttering with possible relationships with sickling and cerebral malaria in childhood is fortuitous (Goodall and Brobby 1982). The fact is, stuttering in Ghana especially is highly correlated with left-handness, which is socially disadvantageous. Relatives heckle and bully the left-hander for doing household jobs with the left hand. On top of all this the nervous left-hander is forced in school to write with the right hand, evoking a constant state of agitation. The desire to excel against all odds is great, so left-handers are very good at their studies, especially mathematics. Any academic institution will find a high proportion of left-handers. In northern Nigeria 30 % of them will be sicklers because 30 % of the rest of the population are sicklers.

Goodall and Brobby (1982) quite rightly caution their readers that their numbers might be too small. It was a fact that 80 % of 5 consultants in the haematology department of a famous African teaching hospital had the sickle cell trait (AS), but could this be used to prove anything? Ghana and Nigeria have the highest incidence of twinning in the world; Ghana boasts the highest incidence of extra digits at birth, the highest incidence of hereditary deafness in one village (David et al. 1971), the highest alpha-thalassaemia rate, the highest stuttering rate, the third highest combined beta-chain mutant rate (S + C + F + K + G) in the world; 1 in 4 males have G-6-PD deficiency etc. One should hesitate to put it all to malaria. Basson (1979) discusses genetic disease and culture patterns in Lebanon. As mentioned before, African anthropogenetics needs rethinking more on factual lines than on theoretical evolutionary concepts (Konotey-Ahulu 1980).”
© Konotey-Ahulu, F.I.D (1991). The Sickle Cell Disease Patient. London: MacMillan: ISBN 0333­39239-6 & Tetteh-A’Domeno Co, Watford 1996, ISBN 0-9515442-2-5 pp 106-108.