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Human populations are afflicted by a number of heritable diseases caused by recessive genes which, although usually rare, together add up to a significant problem. So the question is whether, for eugenic reasons, anything could or should be done about it.
Already a lot of more or less serious hereditary conditions can be identified, together with the effect that these may have on the expectation of life, and on the prospects for any children, which leads to the so-called “insurance dilemma”. Since an independent medical examination is usually required before a life can be insured, if this reveals seriously life-threatening conditions insurance may be refused, or accepted only at an increased premium; which is bad luck on those who, usually through no fault of their own, do represent an increased risk. But why should they be subsidised by increased premiums payable by the rest of the population whose risks are known to be lower? That of course is already done with the National Health Service financed by general taxation, which does its best to help those suffering from medical misfortune, but it is unrealistic to expect that this should ever be able to provide more than some minimum of support. So private insurance companies are in business to offer more than that, paid for by individuals’ premiums: but they do require some assessment of the risks they are undertaking. No company should be forced to accept what it believed to be an excessive risk, and legislation to compel it to do so would simply mean that it had to demand excessive premiums, or go out of business.
But, apart from this insurance dilemma, with recent advances in biological knowledge people can inform themselves of their own risks, and indeed of any risks they may undertake in marriage. Many might well prefer to remain in ignorance, but arguably that is irresponsible and it would surely be wrong to withhold available information from anyone asking for it. Already some more or less serious genetically heritable diseases are known to be controlled by single genes (alleles). These are usually recessive so the heterozygotes, with one recessive harmful allele and the other normal, are symptomless and do not know that they are carriers. But if two heterozygotes marry, one in four of their children will be homozygous for the recessive gene and show the disease, whereas two will be heterozygous symptomless carriers and one the normal homozygote. Such harmful recessives are rare but the chances that two heterozygotes will marry, although small, do exist and have potentially disastrous results. Harmful alleles, and indeed also beneficial ones, turn up from time to time by gene mutation, at a rate which is seldom much more than one in 100,000, with back mutation at about the same rate. So the chances of a gene mutating in any individual are exceedingly small and, since most harmful alleles are recessive, their effects will not appear until many generations later, when two heterozygotes do chance to marry.
But in fact quite a number of hereditary diseases, though rare enough, are still considerably commoner than could be accounted for by the mutation rate, and the question is why should that be so? This is probably to be explained by the “overdominance” effect, when a recessive allele, which is harmful if homozygous, has some selective advantage over the normal homozygote when in the heterozygote. If that is so, then selection in favour of the heterozygotes ensures that the harmful recessive is not eliminated from the population. This is the price, often referred to as the “genetic load”, which has to be paid for its selective advantage in the heterozygote.
For a few genetically inherited diseases of which thalassaemia is an example, endemic in malarious or formerly malarious coastal regions of Italy and elsewhere, the advantage enjoyed by the overdominant heterozygote is clear enough. Two forms of the condition are known, the first being thalassaemia major, in children homozygous for the defective gene, causing their red blood corpuscles to collapse, producing serious anaemia which is usually fatal in childhood. And secondly thalassaemia minor in the heterozygotes, which is largely symptomless except that the cell walls of the red corpuscles are somewhat weakened, so that they collapse when a malaria parasite tries to get in to complete its life cycle. The resulting immunity to malaria gives the heterozygotes a selective advantage over the normal homozygotes, which are not immune, sufficient to outweigh the disadvantage that one in four of the children of two heterozygotes marrying almost all die before puberty. In some parts of Italy, especially along the Adriatic coast, at least 15 per cent of the population are symptomless thalassaemia minor heterozygotes, and this can now be diagnosed by a simple blood test. So couples there thinking about getting married would be well advised to have themselves tested, since if both of them turn out to be heterozygotes they must expect to lose one in four of their children from incurable thalassaemia major. If all the heterozygotes can be persuaded to marry only normal homozygotes, their children will all appear to be normal, even though one in four of them will be symptomless heterozygotes of the thalassaemia gene. Actually, the incidence of the defective alleles will increase slightly since they will no longer be being removed by the premature deaths of homozygotes, but the disease of thalassaemia major itself will apparently have been eliminated from the population.
“Sickle Cell Anaemia” is another heritable disease, caused by a different gene, endemic in parts of West Africa where it is said that up to 40 per cent of the population are symptomless heterozygotes immune to malaria, who however produce considerable numbers of homozygous children destined to die young of the sickling disease.
As yet few other examples of hereditary diseases caused by genes at a single locus, and maintained in the population by the heterozygotes being preferred in selection over both of the homozygotes, are known. But more of them will probably be identified in the future, when the Human Genome Project has been completed in a few years time. And any harmful hereditary condition occurring at a higher level than can be accounted for by the mutation rate alone is prima facie likely to be due to overdominance, perhaps by the heterozygote being stronger or more fertile than either of the two homozygotes, or for other reasons.
Like most other living creatures, the human population is genetically heterogeneous, with a large number of genes represented by more than one allele having selectively different effects, and this indeed provides the raw material for evolution by natural selection. Overdominance probably has a part to play here, though it is seldom easy to see what this could be, especially as obvious hereditary diseases will not usually be involved. But most important characteristics, such as strength and vigour and intelligence, which to a greater or lesser extent are known to be genetically heritable, are multifactorial and controlled by more than one gene and here overdominance may be important, with heterozygotes superior to homozygotes. It follows from this that to eliminate inferior alleles in order to produce a population homozygous for the best type would in principle be impossible, if it turned out that overdominance ensured that the “best” type is in fact heterozygous. That has important implications for selective breeding in domesticated animals and possibly also if we tried to rid the human population of defective genes causing hereditary diseases. Even if this were possible, and it would certainly present serious ethical problems for humans, we would be well advised to go very carefully lest it turned out that, because of overdominance, the best types are in fact heterozygous.
C B Goodhart