pp. 375-380 in Bioethics in Asia

Editors: Norio Fujiki and Darryl R. J. Macer, Ph.D.
Eubios Ethics Institute

Copyright 2000, Eubios Ethics Institute All commercial rights reserved. This publication may be reproduced for limited educational or academic use, however please enquire with the author.

F8. Some current issues in medical genetics in the UK

Derek F. Roberts.

University of Newcastle upon Tyne, U.K.

At the 2nd International Bioethics Seminar in Fukui in 1992, I endeavoured to put into historical perspective some of the ethical issues posed for society by advances in genetic knowledge, and their applications in clinical genetics in the U.K. We saw that, by locating it firmly as a specialism in clinical medicine so that it was seen to respect the accepted ethics of medicine, clinical genetics had been able to allay many ethical worries, and its concentration in family and preventive medicine dispersed many fears that the new knowledge was being applied in the interest of society rather than of the individual. There was moreover clear precedent for the resolution of most of the apparently new problems for, though the range of ethical and social issues was wide, the applications of the new knowledge were essentially extensions of preceding practice: e.g. termination of pregnancy on account of a fetal genetic condition was previously a procedure applied in a severe obstetric situation. Today there is a clinical genetic service in hospital regions throughout the U.K. and the application of such procedures in the minority of cases where they are required excites little public comment. Instead the topics of discussion have shifted, as a result of the advent of molecular genetic techniques and the awareness of the potential extent of predictive genetic testing. No longer is this solely the concern of the individual. For it has raised issues extending far beyond that of the health and reproductive counseling of the individual and his immediate family. They penetrate into the fields of commerce, economics, social life, law and even politics. These issues concern privacy, consent, the rights and duties of family members, the obligations and expectations of employers and insurers, the right to know and not to know one's genetic status, the attitudes of society on the one hand to parents who opt to continue with a pregnancy where the fetus is affected and attempt to raise a disabled child and on the other to those who decide not to do so. Of such issues, several are currently seriously debated in the U.K..

Insurance

Over the past few years, in a number of countries laws have been passed dealing with the use that insurance companies may make of the genetic knowledge that new techniques may provide of the status of applicants for insurance cover. In the majority this use is restricted, on the grounds of public apprehension that genetic information may be used to discriminate against individuals and so adversely affect the provision of financial security to them and their families. In other countries voluntary restrictions exist, and there has been considerable activity in international bodies. For example, the 1989 resolution of the European Par1iament stated that insurance companies should have no right to require genetic testing or to be informed of the results of earlier tests of applicants for cover, and this was echoed in the recommendations of the Council of Europe in 1992 and 1993. France's National Ethical Committee in 1992 asked for legislation prohibiting access by insurers to genetic information in registries or in medical files, and in 1994 the insurance industry adopted a voluntary moratorium. Belgium (1992) and Norway (1994) prohibited genetic testing or asking about genetic tests for insurance purposes. In the Netherlands the Health Council in l989 recommended prohibition of the use of genetic tests for insurance purposes, and restrictions on the requirement of disclosure of genetic information on applicants and their family members for life insurance and pension plans; Dutch insurers adopted a voluntary moratorium.

In Britain, in December 1993 the Nuffield Council on Bioethics recommended that British insurance companies should continue their then practice of not requiring any genetic tests as a condition for obtaining insurance, that there should be early discussions between the government and the British insurance industry about the future uses of genetic data, and that in the meanwhile there should be a moratorium on requiring the disclosure of genetic data. In 1995, the third report of the House of Commons Select Committee on Science and Technology recommended that the insurance industry be allowed one year in which to propose a solution acceptable to Parliament, and that if it failed to do so, a solution should be sought, by legislation if necessary. In February 1997 the Association of British lnsurers (ABI) published a policy statement. In the section 'Seeking and use of genetic tests', genetic tests are defined for the purposes of this statement as examinations of the DNA pattern to find out if it differs from the normal; in the insurance context a genetic test is one which is regarded as predictive in an asymptomatic individual. The document states that the ABI members for a period of two years would continue not to ask applicants for life insurance to take genetic tests; for life insurance for house purchase purposes up to a total of 100,000 pounds the results of any genetic tests would not be taken into account by the insurance company, but the present practice of considering family history and other medical information on the applicant would continue; for new applications for other life insurance policies, individual companies would decide whether or not they wish to take account of genetic tests previously performed. The ABI is keeping this policy under review, has set up its own genetics committee to give advice, and has established communication with interested bodies outside the insurance industry such as the British Society for Human Genetics. Of particular importance, the ABI document is being considered by the Human Genetics Advisory Commission which has been established as an independent body to watch over developments in human genetics and to report to the Ministers of Health and Industry, subsuming the responsibilities previously taken informally by professional associations such as the Clinical Genetics Society. There is thus in place an extensive network of discussions among interested parties to comment on current practice as a preliminary to future legislation should it be considered necessary. In Britain, the preference has generally been for voluntary methods of control, codes of practice, advisory groups and licensing rather than for statutory legislation; for if behaviour is regulated by legislation, then there have to be subsequent modifications to deal with the unexpected that always seems to occur with the passage of time.

Like other forms of insurance, life insurance is based on risk and good faith. That an individual will die at a given date cannot be foretold; however the basic risk of his doing so can be calculated from the mortality statistics available for the population as a whole. Deaths from genetic disease as a whole are already included in the general mortality risk. That basic risk is modified by factors such as the individual's sex, age, life style, smoking habits, health etc. to give a personal mortality risk. Increase in the premiums that an applicant has to pay is the traditional way by which insurance companies provide cover for an applicant at increased risk, for example where both parents died young from heart disease, or where he is a heavy smoker, or where he fails to meet specific health criteria confirmed on clinical examination. The second essential item is good faith, on both sides. The applicant believes that the insurance company will invest the premiums wisely, so that they accumulate and will pay the proceeds in due course to him or his estate. The company expects that the applicant has disclosed all relevant information that will allow a proper calculation of the risks involved and the premium to be charged. From the point of view of the insurance company, the genetic status of an individual can be seen as a relevant variable if the presence of a gene for a particular disease denotes that he will die from it or develop it by a specified age. Thus there appears to be a conflict here between the interests of the insurer and laws prohibiting his use of genetic tests results. He may argue that society sees no objection to his using clinical data as the basis on which he decides whether or not to accept cover, i.e. the present obvious health status of the applicant; nor to his including in that clinical appraisal information that is not obvious but obtained by tests of tissue samples, e.g. cholesterol levels, to determine whether there is excess risk. Why then should he not use other details that are not obvious but obtainable by specialist techniques? It would not require many individuals with 'bad prospects' (i.e. at high risk) to insure themselves for large amounts to distort the ratio between sums paid out in claims and sums received from premiums and investments. From the public point of view there is concern that results of genetic tests may lead an insurance company to refuse cover or charge disproportionately high premiums; but if a higher premium is not charged, is it fair to the other clients who are at normal risk and pay normal premiums? Other concerns are that if insurance companies insist on requiring the results of genetic tests, this may deter people from taking tests which may be to their advantage; and that insurance companies might not have the relevant expertise to deal with the implications of genetic test results.

Looking ahead, whether or not legislation on insurance and genetic information is implemented, it seems that there are two essentials. The first is to view the problem in perspective. By comparison with the enormous number of insurance contracts written each year, those which involve individuals with a genetic problem are relatively few. As brought out in a joint discussion of the Institute of Actuaries and the Royal Society in September 1996, genetic testing would be likely to have less effect of life insurance than on health and long-term care insurance. Moreover genetic tests can only help to define risk, they are not absolute. To assume that those with a given DNA sequence will inevitably develop a disorder and those without it will not is crass. Biology has shown in other organisms the existence of complicating factors such as controller genes, modifiers, gene interaction, position effects etc., which in clinical genetics manifest in reduced penetrance and variable expressivity (respectively the absence of effect of a gene that is present, and variation in effect of a gene). Even in Huntington's Chorea, which is usually taken as 100% penetrant by the age of 70 and 60% by the age of 50, there are cases where the expanded DNA sequence responsible for the disease is not detectable by standard PCR methods on account of a small deletion in the region of' the primer attachment site, so that somebody with the gene would be reported as a noncarrier (Gellera et al., 1996). The second essential is prospective research, to establish the age progression to full expression of a genetic disease from its determinant, a DNA sequence. Such information would be highly useful for people with family histories who wish to apply to insurance, for it would help assign the level of risk attaching to them. Harper et al. (1979) calculated the probability that somebody at an a priori 50% risk of Huntington's Chorea from his family history would manifest it by a given age (ignoring age at parental onset). Such prospective data are few, difficult to collect and analyze, and there are complications of the extent of the variation that there is between and within families, and of the considerable difference that there is in some disorders between age of onset and age at first detection or diagnosis.

Genetic testing of children

The discussion of insurance and the use of genetic information illustrates the system which has evolved in Britain for dealing with such issues. Another example illustrates a further essential point.

Presymptomatic diagnosis is possible for a number of genetic disorders by appropriate medico-physical techniques e.g. adult polycystic kidney disease by ultrasound scanning, familial adenomatous polyposis coli by sigmoidoscopy, some haemoglobin disorders by haematological examination. Whether it is feasible however depends on the age of the subject. By contrast, testing by molecular methods can be carried out at any age, prenatally, in children, or in adults. The Clinical Genetics Society in Britain appointed a Working Party to examine current attitudes, practices and difficulties encountered in the genetic testing of children, and to make recommendations about future practice. It made a series of surveys, retrospective and prospective, of molecular and cytogenetic laboratories engaged in clinical diagnostic work; of attitudes and practices in a large number of health professionals; experiences in family and patient support groups; and altogether its enquiries covered several thousand individuals. Its report (l994) made a number of recommendations, which have now been incorporated in formal guidelines (Fryer, 1997), for example that predictive testing of children is appropriate where the onset of the disorder usually occurs in childhood, or useful medical intervention can be made; it should not be undertaken for an adult onset disease if the child is healthy and if there is no useful medical intervention that can be made if the test proves positive, for such tests should await adulthood when the request can come from the person concerned. These recommendations echo that changes that have occurred in the law, e.g. the Children Act 1989, so that parents now have responsibility for the care of their children rather then rights over them and are expected to act in their best interests.

In one of the surveys clinical geneticists and consultant paediatricians were asked whether they would test a five-year old child for predictive or carrier status at the request of its parents. A selection of the results was reported at the Fukui Bioethics Seminar in 1993 (Clarke, 1994). There was considerable variation in the answers according to the disease e.g. predictive testing would not be carried out for prion protein dementia by 100% of geneticists and for Huntington's chorea by 96%, but for Marfan's syndrome by only 8% and for hyperlipidemias by 15%. The corresponding figures from the paediatricians were 42%, 47%, 11% and 7%. Paediatricians were generally much more willing for genetic tests to be performed in childhood than the geneticists. The reasons for these variations within and between the two specialties remain to be analyzed, but it seems that the most important factor was the respondent's attitude to such testing in general rather than the availability of early treatment or surveillance for complications. The questions were of course hypothetical, for in the real life situation the response would be modified to take account of the particular circumstances of the family. But the results nevertheless show that, as with so many questions of ethics, there may be considerable variation in opinion among individuals and among cases yet an acceptable consensus on principles can be reached. It is such variation that makes medicine an art rather than a science, and that makes statutory legislation so difficult.

From the ethical point of view, the arguments against testing of children are that it deprives a child of the right to decide for himself whether or not to be tested as an adult when he will be more capable of appreciating the implications of the findings, that the confidentiality to which an adult is entitled is breached by informing the parents of the result, that the testing breaks the policy of counseling beforehand and afterwards, and that a positive test may lead to future discrimination by insurers and employers and may distort the child's self-esteem and his relationships with others within and outside his family. Yet there may be benefits psychologically in passing the information to the child not in a single shock at the difficult time of late adolescence which would occur if testing is deferred until then, but if the parents do so gradually over a period of years in the normal process of preparing him for adult life.

Commercial testing

A topic that is beginning to be discussed is that arising from the availability of genetic testing direct to individuals by private companies. In Britain such commercial facilities have not developed as far as in the United States, where problems are already emerging. A laboratory in North Carolina failed to offer proper counseling before testing clients for a colon cancer gene, and gave incorrect interpretations of the results in nearly one-third of cases (Giardello et al., 1997). In Britain so far there are two such companies, offshoots of work in university laboratories in Leeds and London. A factor in their establishment has been the lack of funding in National Health Service and university laboratories to cover all such tests required, together with changing political concepts of administration and financing of hospitals.

This matter is under consideration by the Advisory Committee on Genetic Testing. It felt that there is a very real danger that unscrupulous companies may prey on the public's fear of disease and genetic disorders and offer inappropriate tests, without adequate counseling and even without the laboratory and personnel facilities to, ensure that the tests are conducted accurately. At present there is no way to prevent this. The Committee recommended as a matter of urgency that there should be a body able to regulate companies offering genetic testing through a process of protocol review and licensing, and that the government should take steps towards such regulation, if necessary by primary legislation. In the meanwhile the Committee has drawn up a code of practice, adherence to which is voluntary but any failure to conform by any company would be announced in the Committee's annual reports. The code requires compliance with standards of confidentiality and good laboratory practice. All clients should receive counseling before and after the test to make sure that they understand it and its implications. Only those tests may be used that are supported with solid clinical data.

Patenting of DNA sequences

There has been strong controversy over the question of patenting of DNA sequences, for several reasons - the commercial involvement, the practical and ethical implications, the variation in patent laws in different countries. In Britain a joint statement as issued in 1994 by the several professional societies concerned with different aspects of clinical genetics indicating that in principle they were against the granting of patents on human gene sequences. In March 1995 a European Union Commission draft directive on the legal protection of biotechnological inventions was rejected by the European parliament. The new directive which replaces it states that the human body and its elements in their natural state shall not be considered patentable inventions; nevertheless, the subject of an intervention capable of industrial application which relates to an element isolated from the human body or otherwise produced by means of a technical process shall be patentable, even if its structure is identical to that of a natural element. In other words it makes provision for the grants of patents on human gene sequences provided that they are isolated from the human body. If this directive is adopted by the European parliament, all member states will have to ensure that their national patent laws comply.

The Science and Technology Committee in Britain examined the moral, technical and research Arguments. Ethical arguments against patenting are that many people feel that such patents reduce human beings to the status of 'biological machines', and confer rights of ownership over a part of the human body; that the knowledge of gene sequences patented is obtained through the cooperation of many people i.e. those who have given DNA samples so that a cure can be sought for diseases from which they or their relatives suffer, and those whose researches have contributed small pieces of relevant information, and it is wrong to allow this knowledge to be appropriated by a single entity and used for profit. Counter arguments are equally strong. The committee found that there is a role for patenting in the application of the results of genetic research. It concluded that only a combination of a gene and a known utility which is novel and not obvious should be patentable in the context of that utility, that a combination of the same gene and a further novel utility should also be patentable, but that fragments of genes and gene sequences of unknown function should not. It was concerned that patent examiners are applying the criteria of utility and novelty too loosely, and that in the absence of a consensus among different countries on harmonizing patenting law, the imposition of a directive could be more harmful than the current differences in criteria of patentability.

Conclusion

There is currently in Britain widespread awareness of the numerous ethical problems posed by recent advances in human genetics and their applications. Thanks to television and the popular press, it is found in the population at large as well as in those in the health professions and in families with genetic disease. A network of interacting committees, set up by initiatives from parliament, professional associations, research bodies and other interested groups, has evolved. Their function is to watch over developments and practices, ensure full discussion, make recommendations, draw up codes of practice, and help prepare for legislation if it is thought necessary.

Acknowledgment

Acknowledgment is gratefully made to Professors Martin Bobrow and Marcus Pembrey for their helpful discussions.

References

1. Roberts, D. F. 1992 Medical genetics, social issues, and the genome programme, pp. 98-104 in Fujiki N, & Macer, DRJ, eds., Human Genome Research and Society Proceedings of the second international bioethics seminar, Fukui. Eubios Ethics Institute.

2. Nuffield Council on Bioethics 1993 Genetic screening: ethical issues. Nuffield Foundation, London.

3. House of Commons Select Committee on Science and Technology 1995 Third Report: Human genetics in science and its consequences. London.

4. Gellera, C., Meoni, C., Castellotti, B., et al 1996 Errors in Huntington disease diagnostic test caused by trinucleotide deletion in the IT15 gene. American Journal of Human Genetics 59 475-477.

5. Harper, P., S., Walker, D. A., Tyler, A., et al 1979 Huntington's Chorea: the basis for long term prevention. Lancet 2 346-349.

6. Clinical Genetics Society 1994 Working Party Report: The genetic testing of children. Journal of Medical Genetics 11 785-787.

7. Fryer, A. 1997 The genetic testing of Children. Journal of the Royal Society of Medicine 90 419-421.

8. Clarke, A. 1994 Genetic testing of children, pp. 218-221 in Fujiki N, & Macer, DRJ, eds., Intractable neurological Disorders, Human Genome Research and Society Proceedings of the third international bioethics seminar, Fukui. Eubios Ethics Institute..

9. Giardiello, F. M., Brensinger, J. D., Petersen, G. M., et al 1997 The use and interpretation of commercial APC gene testing for familial adenomatous polyposis. New England Journal of Medicine 336 823-826.


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