SCIENCE / The cloud of knowing: The new biology Part 3: Ethics

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Imagine this scenario. A young man hears that one of his parents has developed the first symptoms of a distressing and lethal inherited disorder which means there is a 50:50 chance of his carrying the defective gene. A test is available to settle the matter, but he decides he would rather not know. However, his wife is pregnant and she wants a prenatal test to see whether her unborn child has the gene. If the test is positive, and she decides to terminate the pregnancy, her husband will know he also carries the gene. If she has the right to know, what about her husband's right not to know?

This is not a hypothetical situation. The disease in question is Huntington's chorea, a genetic disorder that causes severe dementia, behavioural abnormalities and eventual death. It usually occurs between 15 and 20 years after the first symptoms appear. Huntington's disease results from inheriting one defective copy of a gene that scientists have yet to identify although they know its approximate 'address' on one of the 23 pairs of human chromosomes. This has led to the development of a reasonably reliable test which can identify most carriers. If you carry the gene there is no dispute about what lies in store: you will die prematurely after many years of progressive illness and there is no cure.

Ethical dilemmas posed by the new biology are best illustrated by the 'time-bomb' nature of Huntington's disease. The test not only identifies carriers, it accurately predicts what will happen to them in later life. It is this predictive nature of the new biology that causes most concern among people worried about the social implications of widespread screening for genetic diseases. 'A lot of the ethical dilemmas of the new genetics are not much different from before,' says Professor David Weatherall, director of Oxford University's Institute of Molecular Medicine. 'We've been able to offer parents a choice of whether to terminate pregnancies on grounds of genetic abnormalities for years. The new ethical issues come from predictive genetics.'

Take another scenario, this time set sometime in the first half of the 21st century. A young, healthy patient visits the doctor to receive a computer read-out of his or her pre- disposition genes, a genetic profile which determines the risk in later life of developing heart disease, high blood pressure, alcoholism, cancer and a range of other life-threatening illnesses. From that moment on, the person will know what it is they are likely to die of and what measures they can take, if any, to delay or avoid the fate laid down in their genes. The information may be confidential, but third parties such as employers or life insurance companies will also be interested to know about the genetic predispositions of potential employees or clients. It is not such a fantastic scenario, as Professor Weatherall says: 'An insurance company now can ask your blood pressure, weight and whether you smoke. I'm not clear why they shouldn't be able to ask in 100 years' time what your coronary artery profile is.'

IN the case of Huntington's chorea, the ethical issues are already being confronted. Because of the delayed nature of this disease, it is

perhaps not surprising that few people at risk of Huntington's chorea have volunteered to be tested. Between 1987 and 1990, for instance, genetic counsellors in the UK carried out

248 tests for the Huntington's gene out of an estimated 10,000 people who have a parent with the condition and who are therefore at 50 per cent risk of the disease. (Two-thirds of those who volunteered for tests were women.)

Peter Harper, professor of medical genetics at the University of Wales College of Medicine, Cardiff, works on the genetic basis of Huntington's chorea and says he feels 'uneasy' about the possible misuse of advances in the new genetics. Widespread testing for genetic abnormalities risks stigmatising carriers of defective genes, unless effective education is done in conjunction with it, he says. There is also the issue of whether it will ever be right to test children who are at risk of genetic disorders in later life, such as Huntington's chorea. 'I can think of no more important issue which has been so ignored by those professionals who ought to be most concerned.' Every baby has a pinprick of blood taken at birth to detect treatable disorders such as phenylketonuria, where a build-up of a substance in the blood causes brain damage, he says, 'but what rules should govern its use for detecting late onset and untreatable disorders?'

Last year, Professor Harper wrote an editorial in the American Journal of Human Genetics highlighting past abuses of Huntington's chorea patients earlier this century in the US and, more specifically, in Nazi Germany. Health professionals, he said, should be 'sensitised to the issues and potential dangers' that led to the abuse of genetics in history which culminated in enforced sterilisations. 'While the kind of systematic and deliberate abuse that Nazi Germany practised on patients and families with Huntington's disease (or other genetic disorders) is difficult to envisage occurring again at the present time,' he wrote, 'it would be most unwise to discount the possibility, particularly when one considers the power inherent in new developments in genetics.' Gene- hunting technology and computerised registers of genetic information would both have proved invaluable tools for the Third Reich, he says, had they existed in the 1930s.

NOW that these tools are available, however, it will inevitably lead to widespread screening for defective genes in the population at large. In fact 'community genetics' is well established within some ethnic groups at risk of certain disorders, such as sickle-cell anaemia among black people, Tay-Sachs disease in Jews and thalassaemia in Cypriots. Recently, with the discovery of the cystic fibrosis gene, screening of the wider population for healthy carriers of this common disorder has begun in several trials in London, Edinburgh and South Wales. Because the gene is recessive - it needs two copies, one inherited from each parent, to cause the disease - doctors believe there may be advantages in testing the public for carriers so they will know the risks, if any, of having affected children. (Two carriers have a one in four chance of having an affected child.)

The possible pitfalls of mass screening have been highlighted, however, by the results of one of the first studies into its effectiveness. Martin Bobrow, professor of paediatric research at Guy's Hospital, London, organised a survey of 1,000 people for the defective cystic fibrosis gene and called on the help of a pyschologist to assess their reaction. He found a 'significant minority' failed to understand completely the nature of the test even after being educated about it. Despite being told that the test was only 90 per cent reliable, for instance, some people came away believing that a negative result meant that they were definitely not carriers of the defective gene. Others who were told they were definitely carriers somehow misconstrued this to mean it was only 'quite likely' that they were carriers.

A further problem, particularly if the genetic tests are done on a population-wide basis, is the question of confidentiality. Technically, anything written down on NHS paper is government property, including, presumably, the results of a genetic diagnosis. Who is to be the guardian of this new source of sensitive information and what measures will be needed to protect it against abuse by third parties?

It is clear that life insurance companies already believe it is proper for them to ask for medical information about potential clients and they are becoming increasingly interested in the prospect of genetic tests, particularly for 'predisposition' genes that increase the risk of life-threatening illnesses such as cancer and heart disease. John Wagstaff, of the Association of British Insurers, says there is as yet no suggestion that insurers would seek tests from clients, but they would nevertheless want to know the results of any that have taken place. 'It's part of the medical record and is therefore exactly the same. It's only by getting the information that we can disregard it.'

THE BRAVEST of all new worlds is the prospect of scientists manipulating human genetic material, selecting beneficial traits and eliminating defective ones at the earliest stages of human development; the sperm, egg or embryo. Ethicists have opened the debate on how far we should allow the new biology to tinker with human inheritance.

Dr John Habgood, Archbishop of York and himself a scientist, has been prominent in highlighting the issues. 'It is important to start with people as they are, with their genetic diversity, rather than to label people on the basis of genetic categories.' Gene therapy - the replacement of defective genes with healthy substitutes in non-reproductive tissue - is acceptable, he says. 'But a line will need to be drawn in the future between therapy to cure clearly defined genetic diseases, and less clearly defined and ethically unacceptable attempts to 'improve' human beings. In particular we must ask whether there is a core of human personality which should remain inviolate.'

Already the government committee set up to investigate the ethics of gene therapy, chaired by Sir Cecil Clothier, has ruled that manipulation of human genetic material should be restricted to the alleviation of disease and should not be used to change or enhance any normal human characteristics, such as differences in height. (Already there is a body of scientific opinion that believes it will soon be possible to identify genes that are responsible for intelligence, musical ability and other aspects of what we call 'giftedness', which throws up the nightmarish scenario of a Frankenstein creating the perfect human being.) The committee has also ruled that manipulating the genes of human reproductive cells should not 'at the moment' be attempted 'because there is insufficient knowledge to evaluate the risk to future generations'.

It is highly unlikely that this will always be the case, as research on animals has shown. By eliminating defective genes at the stage of sperm, egg or early embryo, scientists can, in theory, stop human disorders being transmitted to future generations (although total elimination from the population may be impossible as spontaneous mutations will always arise). Sir Cecil himself sees the advantages: 'I don't think there is anything morally outrageous about being able to prevent transmission (of disease) to future generations.' The problem, he says, is that not enough is known about the repercussions of gene therapy in reproductive cells - so-called 'germline' therapy.

Professor Weatherall at Oxford also believes we must leave the door open for germline therapy. 'Surely it is quite impossible for one generation to lay down hard and fast rules about what may not be acceptable in, say, two or three hundred years' time.' It is essential, he says, to begin a public debate on where we are going in manipulation of human genetic material because 'it is much too important a subject to be left to scientists and politicians'.