Heredity: Science and Society; on the possibilities and limits of genetic testing and gene therapy

Introduction

This report was prepared by our committee on request of the government, as stated in a letter of February llth, 1988. The report covers the current state of knowledge and the social, ethical and legal implications of genetic testing and gene therapy. We looked into various issues, considering their consequences for individuals as well as for society as a whole and for groups within it.

Congenital and hereditary abnormalities are a major cause of human illness and death; in the first year of life, they are the main cause of death. An estimated 4 to 6 per cent, of full-term babies have a congenital or hereditary disorder. Some of these are so minor that they present no problems, while others can be remedied by appropriate treatment. Most, however, cannot be helped.
Heredity also plays a role in illness and death in later life. The susceptibility of predisposition to cardiovascular disease and cancer, the main causes of death in older people, have been shown to be influenced by hereditary factors.
The scale of the problem of congenital and hereditary abnormalities justifies an increased emphasis on research in this field. Our rapidly-accumulating knowledge of the structure and function of the human genetic material will also improve out understanding of the causes of congenital and hereditary disorders.
In the following sections, we review briefly the different topics which will be addressed in the report.

Genetic testing and genetic counselling

There are currently eight centres for clinical genetics in The Netherlands, closely linked with teaching hospitals and university laboratories. These centres carry out genetic testing, including pre- and post-natal chromosome analysis, biochemical testing and DNA typing, as well as providing genetic counselling and support following the testing.

Genetic counselling

Our committee would like to emphasize that the main purpose of genetic counselling must be to provide clients with information, especially concerning reproductive matters. This information must enable individuals to make choices acceptable to themselves, in their own situation, in accordance with their own beliefs. The information provided must also be neutral; it is not for the counsellor to give unasked-for advice.

Role of the State

The role of the State with respect to genetic testing and counselling includes at least the promotion of the right to choose for oneself, and therefore the freedom of the individual to decide for him/herself. This also implies support for the provision of information to the public, for guarantees of accessibility to services and for quality control of these services.
We do not condone any coercion on the part of the state to induce individuals to undergo genetic testing nor to take preventive measures. Such action would be in contradiction to fundamental principles of law and of human rights.
Concerning access to prenatal chromosome analysis, our committee does not find that there are sufficient grounds for reducing the present age limit in The Netherlands (36 years). We would also oppose any restriction of access to such testing, for example by limiting it to women who are willing to agree in advance to terminate the pregnancy if an abnormality is found in the foetus. The arguments sometimes proposed in favour of such a policy, for example that the facilities for this service are few and costly, cannot justify its implementation. Moreover, prenatal diagnosis is not meant to be aimed at termination; its purpose is to provide pregnant women and their partners with information. Restricting access to this information would give rise to inequalities in human rights.
Many objections can be raised to the uncritical use of cost-benefit analyses to solve the problem of distribution of the scarce resources for genetic testing and screening. Neither the costs nor the benefits can be established with any certainty, and the contribution to human welfare cannot be expressed in positive or negative figures.
Our committee considers the present standards of quality and of quality control to be satisfactory. We do, however, recommend that DNA analysis using simplified technology (DNA test kits) be restricted to laboratories in centres for clinical genetics. Only these centres possess the necessary expertise, not the least of which is their ability to provide the support needed because of the far-reaching consequences of some test results for those involved.

Ethics and law in genetic testing

Among the many ethical and legal aspects of genetic diagnosis, our committee has concentrated in this report on the client’s right to information, his/her right not to be informed, the right to confidentiality, protection of privacy, and provision of information to family members.
We find that the principle of an obligation to provide information must be fully respected. Exceptions are permissible only if and to the extent that the client is likely to suffer serious harm, or where the professional obligation of secrecy towards a third party takes precedence.Similarly, the right not to know may be infringed upon only in extreme situations.
The question of confidentiality with respect to family members brings certain dilemmas to light, for example, when the need to approach family members for information infringes on their privacy, or when a family member refuses to agree to give information which is relevant for the client (using his/her own right to confidentiality).
In general, our committee urges extreme caution in revealing information about the client and in disclosing such information to relatives. The privacy of the relatives must also be closely guarded. We would accept an infringement of these various rights only in exceptional circumstances, and then using a ’conflict of duties’ approach, in which case there must be a reasonable certainty that the breaching of confidentiality is necessary to prevent or to minimize serious harm to a third party.
The possible legal liabilities of the professionals involved do not, in our view, raise problems fundamentally different from those affecting other kinds of professional assistance.

Genetic registries

Genetic registries and the use thereof must be limited to the strictly necessary. Persons appearing in such records are protected by the rights spelled out in present and future laws on this subject. In particular, it is important that the recording and storage of genetic information only be done with the permission of the individual involved. Our committee also stresses the importance of the right to have information deleted from records, or to have it stored anonymously.
We recommend the development of provisions to protect the rights of family members appearing in genetic registries, to avoid problems with their rights (Data Protection Act). Detailed regulations governing the storage of especially sensitive data, as envisaged in the Act, will provide a framework suitable for the protection of personal genetic data in general, both within and outside the health care system.

Cell banks

The rights of the ’donor’ of body tissues or cellular material must of course be respected. This does not mean, however, that unnecessary barriers should be erected to the use of such material for the benefit of other persons, or for research. We propose that a code of conduct be drawn up, in which the rights of donors would be specified. How these rights are to be put into effect should be covered by a written agreement at the time the material is obtained. The agreement must specify such aspects as the storage and use of the material, and the considerations of confidentiality and privacy.

Mass screening

Certain inherited metabolic disorders can be detected by neonatal screening. Newborn babies in The Netherlands are presently screened for phenylketonuria (PKU) and congenital hypothyroidism (CHT); for both disorders, effective treatment is available. Screening for other conditions, discussed in this report, could lead to timely genetic counselling and improvements in treatment prospects. Our committee opposes, however, neonatal screening for untreatable, late-onset conditions because this would only burden the child with distressing information. Similarly, screening for disorders that present during childhood is not recommended when diagnosis is unreliable and effective treatment unavailable.
Although it would already be technically possible to carry out large-scale screening of adults to identify carriers and genetic defects, there are important limitations to this approach. These include genetic heterogeneity, and the lack of sufficiently reliable and practical methods of detection. Our committee feels that the application of large-scale screening requires careful deliberation, especially to ensure that the benefits outweigh the disadvantages.
Within a few years it will probably become possible, by means of mass screening, to reliably identify carriers of cystic fibrosis, a recessive hereditary disease affecting 1 in 3,600 newborns in The Netherlands. (The present tests are not reliable for mass use.) An estimated 1 in 30 persons may be carriers. When both partners in a couple are carriers, they should be informed of the probability (25%) that their child will be affected by cystic fibrosis, and of the possibilities for prenatal diagnosis.

Genetic testing outside the health-care system

Insurance

We have formulated, in this report, measures related to genetic testing in the context of access to life and disability insurance and to personal pension schemes. To avoid unacceptable consequences for insurance clients while minimizing the risks to insurers of ’self-selection’ among clients, we advocate a ban on genetic testing in this situation, as well as restrictions on the requirement to disclose information from previous genetic tests. Further investigation of the European legal context is necessary.

Employment

Our committee rejects, in general, the use of tests of genetic predisposition in selection of employees. Exceptions to this rule should only be considered, if in the future sufficiently reliable tests are developed, where the health interests of the individual concerned, or of a third party or parties, are demonstrated to be at risk. Such genetic testing in employee selection was also considered unacceptable by the Interdepartmental Working Group on Employment Medical Examination. The criteria drawn up by the Working Group in 1989 should be reinforced and supplemented by the addition of a general requirement that testing must not result in unfair distinction between or discrimination against groups within the society. If the Working Group’s recommendations, thus amended, are not implemented in the near future through self-regulation, we believe that legislation is required.
In principle, genetic screening and monitoring in the place of employment could enable detection of increased genetic susceptibility to disease, and diagnosis of damage to genetic material due to environmental/occupational factors. This information could lead to preventive measures. The methods available for such research, however, are not yet sensitive enough for large-scale application.

Looking ahead

Pre-implantation testing

The views of the committee members differ as to the permissibility of experimentation on pre-implantation embryos for development of pre-implantation diagnostic techniques, one of the issues involved being the question of the intrinsic value accorded the pre-embryo (and thus its need for protection).
Were such experimentation to be permitted, the question would arises whether only surplus pre-embryos from in vitro fertilization (IVF) programmes may be used, or whether pre-embryos may be created for the purpose of research. On this point the opinions of the members of our committee also differ, even among those who agree that such research is permissible in principle. Leaving aside the latter question, the majority of the committee regards such experiments as permissible in the context of specific requests by a couple for assistance, providing strict conditions are applied.Caution is, however, urged in this matter.

Gene therapy

Correction of genetic abnormalities at the DNA level is still in the laboratory research stage. Nonetheless, the first clinical trials of somatic-cell gene therapy are expected to start within the next few years.* Germ-line gene therapy, in contrast, is at this time no more than a theoretical possibility.
Although somatic-cell therapy is still in an experimental stage, we judge that when that stage has been passed, this type of therapy does not differ essentially from other forms of medical treatment, such as organ and tissue transplantation. Since development is still experimental, our committee will, in this report, formulate certain substantive and procedural conditions.

Germ-line gene therapy involves such uncertainties about the risks to human beings that we consider a moratorium on such research necessary.

* Note added in the translation: the first trials have started in the mean time.