Steve Jones - The Language of the Genes

Galton, no doubt, would approve the many conceptions that arc ended for genetical reasons. In the end, what genetic screening achieves will be limited by attitudes more than technology. They can be hard to predict. In the bad old days, Germany was much at fault; but liberal Sweden sterilised sixty thousand in a programme that lasted long after the end of the War. As late as 1995, South Australia's Reproductive Technology Act forbade treatment for infertility to those who had faced criminal charges. Britain, in contrast, the home of the whole idea, never put eugenics into practice. Ninety-five per cent of the twenty-first century's children will be born in the third world. Although in most places genetics has still to make an appearance, China already has a well-established service. In 1993 the country passed a law that was designed to 'put a stop to the prevalence of abnormal births and heighten the standards of the whole population'. Most of the country's geneticists are in favour of compulsory tests before marriage, and of pre-natal diagnosis of severe genetic diseases (with the implication that a termination is called for).

Elsewhere, though, attitudes can be unexpected. Sardinia is a rather traditional Catholic society in which many marriages risk having a child with thalassaemia. Nine tenths of the couples who face that predicament now know this; and when the woman has an affected foetus nine tenths of those choose termination. Tests offered to older mothers in Denmark led to a fivefold decrease in the number of Down's Syndrome children. Perhaps illnesses such as Huntington's will soon become rare as those at risk decide not to reproduce. Some of the most enthusiastic campaigners for tests for inborn disease are parents who have had an affected child. That in itself says something about where the ethical balance lies. In some places though, such is the passion for the 'right to life' that charities who appeal for funds for genetical research never mention the idea of abortion, but instead concentrate on the {often hopeless) search for a cure.

Genetics as a negative force embodies another subtle tyranny; the dictatorship of the normal, the pressure to produce an average child. The United States has seen demands for growth hormone to be given to children who grow up a few inches shorter than average aiul would once have been accepted as ordinary. One in len Unions would consider termination of pregnancy for a foetus found to have two missing Hngers; and, in a mirror image ol genetic discrimination, a majority of deaf people claim th;t(ihcy should have the right to prefer the birth of a deaf child who might fir better into their family. Achondroplasia, the common form of dwarfism, arises from a dominant mutation. It has some effect on the health of those who bear the gene, but most of the time they are well, and many are positively proud of their condition. Almost all cases arise from new mutations and are born to parents who had no idea of the risk. The gene has been found. Any pregnancy in which the child appears to be growing slowly is monitored. At first, to find that the growth problem was due only to achondroplasia was seen by doctors as useful reassurance to the parents. Many physicians were alarmed to find that the response was often to demand a termination. Now, some centres do not reveal the results — but who has the right to conceal the truth?

Achondroplasia is a reminder that genes involve people as much as DNA. That lesson has been learned again and again. The first attempts to use the new knowledge ran into difficulties because they ignored social realities. A search for carriers of the sickle-cell gene in the American black community thirty years ago led to great bitterness. Although carriers are quite healthy except in conditions of extreme oxygen shortage (which few experience) some states made screening compulsory. Those carrying one copy of the mutation were discriminated against in jobs and for insurance. Even worse, people who did not carry sickle cell considered those who did to be less healthy and less happy than did the carriers themselves. The carriers were discriminated against when it came to marriage and the programme gave hints of eugenic attempts to improve the quality of the population rather than the health of individuals. The scheme — albeit conceived with the best of motives — was a model of the way in which genetic information should not be used.

Even so, the genetic inquisition is here to stay. Why not, after all, extend testing to the adult population, for their own good or for that of society and leave society to work out how to deal with the difficulties as they arise? The history of discrimination against the genetically unfortunate is a miserable one: but, after all, that was long ago. Would not someone at great risk of heart disease like to know before real damage is done, in time to choose his vices to reduce the risks or to ask for early treatment? The idea is seductive and much-discussed. The truth, alas, is not always so simple, for several reasons.

How far testing can go is set first by the pervasiveness of imperfection. Any recessive disorder always involves far more carriers of a single copy of the variant than of two. If an illness of this kind affects one birth in ten thousand, about one normal person in fifty carries the gene — which means hundred times as many copies in healthy people as in those who are ill. As a result, the notion that one can improve the long-term health of the population by preventing those with inherited disease from having a child is simply wrong. Almost everyone carries one or more different genes for recessive inherited disease. A universal screen would provide information which is unwelcome and is of almost no use.

Take cystic rlbrosis. One British child in two thousand five hundred is born with the condition, so that about two million Britons carry a single copy and in a tenth of marriages one or other of the partners is a carrier. Any screening programme would turn up millions of such couples. If married couples were checked for all recessives, so many carriers would be detected that it is hard to know what to do with the information — or wherher ir was worth gathering in the first place.

That problem is compounded by a dawning realisation that screening itself may be much more difficult than was once hoped. Mendel's laws are so straightforward ih.it the map of the genes should, it seems, make it easy to pick out those at risk. The public — and many doctors — believes as much and demand is strong. It seems that a new era of certainty is near, but at least where genetic screening is concerned the truth is more ambiguous.

There are two main difficulties in this application of simple rules to complex problems. First, for most genetic conditions, the DNA involved can be damaged in a number of ways. Every population — sometimes, every family — may have its own mutation in different parts of a structure that may be tens of thousands of bases long. A test that detects an error in one group hence may not work for others. As a result, instead of a universal screen, many separate checks may be needed. To speak of 'the' test for — say — cystic fibrosis means less than it seems. More important, many inborn conditions, although they run in families, involve several or many genes that come together each generation in shifting constellations whose effects are hard to predict.

For single gene conditions such as cystic fibrosis some mutations happened long ago and have spread to millions of people. Others took place recently, and are found in just a few. In general, the older a mutation the wider it spreads and the easier it is to generate a useful test. For the hundred or so Mendelian diseases so far studied in detail, the news is not particularly good: most have high diversity, most individual mutations are rare, and — at a guess — the majority of errors have appeared within the past two thousand years and are still restricted in their spread.