3. Ethics in genetic research and practice

3.7 Summary of recommendations

3.7.1 Gene therapy

3.7.1.1 Somatic cell gene therapy
It is recommended that somatic cell gene therapy should be governed initially by the exacting requirements that already apply in South Africa to other research involving human subjects.

While the safety and effectiveness of somatic cell gene therapy are still uncertain, this new treatment, as with any other treatment, should be limited to patients in whom the potential for benefit is greatest in relation to possible inadvertent harm. It is recommended that the first candidates for gene therapy should be patients in whom the disorder is:

1. life threatening or causes serious handicap;
2. one for which treatment is at present unavailable or unsatisfactory.

3.7.1.2 Germ-line gene therapy
Gene therapy should be directed to alleviating disease in individual patients, although wider applications may soon call for attention. In the present state of knowledge, any attempt by gene modification to change human traits not associated with disease would not be acceptable.

It is recommended that the necessary research should continue. There is, at present, insufficient knowledge to evaluate the risks, to future generations, of gene modification of the germ line. It is therefore recommended that gene modification of the human germ line should not yet be attempted.

3.7.1.3 Supervision of gene therapy
Continuing supervision of gene therapy is necessary. No existing body has been constituted for these tasks. Therefore, it is recommended that a new expert supervisory body be established.

This supervisory body should be of sufficient standing to command the confidence of existing Research Ethics Committees, and of the public, the professions and of Parliament. It should have a responsibility for:

1. advising on the content of proposals, including the details of protocols, for therapeutic research in somatic cell gene modification;
2. advising on the design and conduct of the research;
3. advising on the facilities and service arrangements necessary for the proper conduct of the research;
4. advising on the arrangements necessary for the long-term surveillance and follow-up of treated patients;
5. receiving proposals from clinicians who wish to conduct gene therapy in individual patients, and making an assessment of:
   1. the clinical status of the patient;
   2. the scientific quality of the proposal, with particular regard to the technical competence and scientific requirements for achieving therapy effectively and safely;
   3. whether the clinical course of the particular disorder is known sufficiently well for sound information, counselling and advice to be given to the patient (or those acting on behalf of the patient) so that informed consent may be obtained (see 5.3 Book 1) - for the outcomes of therapy to be assessable;
   4. the potential benefits and risks for the patient of what is proposed;
   5. the ethical acceptability of the proposal.

In the light of this assessment, the expert supervisory body should recommend whether or not the proposal should be approved. Where applicable, conditions should be stated. The supervisory body should also have responsibility for:

6. acting in collaboration with existing Research Ethics Committees;
7. acting as a repository of up-to-date information on research in gene therapy internationally;
8. setting up and maintaining a confidential register of patients who have been the subjects of gene therapy;
9. oversight and monitoring of the research;
10. providing advice to Health Ministers, on scientific and medical developments that bear on the safety and efficacy of human gene modification.

We recommend that any proposal for gene therapy should be approved by this body as well as by a properly constituted Research Ethics Committee.

Initially, and probably for several years, gene therapy will be applicable to a small number of uncommon disorders and will be confined to a few patients. As with other new, specialised medical interventions, we recommend that it be confined to a small number of centres while experience is gained.

3.7.2 Genetic screening

3.7.2.1 Counselling, providing information and obtaining consent
We recommend that the following ethical principles be applied to genetic counselling:

1. respect for persons and families, and respect for their decisions;
2. preservation of family integrity;
3. full disclosure and provision of accurate, unbiased information relevant to health, to individuals and families;
4. protection of the privacy of individuals and families from unjustified intrusions by employers, insurers and schools;
5. informing families and individuals about possible misuses of genetic information by institutional third parties;
6. informing individuals that it is their moral duty to tell blood relatives of the genetic risks to which they may be exposed;
7. informing individuals of the wisdom of disclosing their carrier status to a spouse or partner if they intend to have children, and the possibility of harmful effects of non-disclosure on the marriage;
8. informing individuals of their moral duty to disclose a genetic status that might affect public safety, for example an airline pilot with epilepsy;
9. unbiased presentation of information, insofar as this is possible;
10. a non-directive approach, except when treatment is available;
11. involving children and adolescents, whenever possible, in decisions that affect them;
12. duty to re-contact as appropriate and desired.³²

Informed consent is a term in the medical field, implying knowledge on the part of the patient, or research participant, of the major characteristics of their medical disorder if they are suffering from one, an understanding of the test or procedure which they are to undergo, the limitations of the test or procedure, and the possible consequence of their participation in the test or procedure.13 This term includes the research participant's or patient's right to be informed of risks not actually related to the medical impact of the test or procedure, including:

"... possible socio-economic consequences of an unfavourable test result, such as loss of health or life insurance, refusal of employment, discrimination by schools, adoption agencies etc. should where applicable, be included under the description of risks."¹⁴

It is recommended that the information to be specified to any patient undergoing genetic screening should include:

1. the seriousness of the condition to which the genetic disorder may give rise, and how its effects may vary;
2. therapeutic options available;
3. how the disorder is transmitted, the significance of carrier status and the probability of developing the serious genetic disease;
4. the reliability of the screening procedure and the results of the test;
5. how the results of the screening test will be passed on to the patient, and what will be done with the samples;
6. the implications of screening positive for their future and existing children and for other family members;
7. a warning to women that the screening test may reveal unexpected and awkward information; for example, about paternity.²⁶

Informed consent in medical research is dealt with in detail in Section 5 of Book 1 in this series. The need to obtain informed consent to participate in research is entrenched in the South African Constitution Section 12(2)(c).

3.7.2.2 The Constitution, public policy and the practice of genetic screening

3.7.2.2.1 Results of genetic screening and confidentiality
It is trite to state that employers and insurers should have only limited rights to initiate screening programmes. This alone will not prevent genetic discrimination from occurring for so long as employers and insurers have access to genetic information.^s (See also 3.3.4.1.1 for references to South African law.)

The best way to ensure that genetic information is appropriately shared with family members (and occasionally with other third parties) is through information and counselling procedures. Although the desirability of sharing information with family members may be emphasised, disclosure ought not to be made a condition of participation in a screening programme. Inevitably some individuals will refuse to allow disclosure, and this may present the health professional with an ethical dilemma.

It is recommended that the following guidelines be adopted with regard to disclosure to families, of the results of a genetic screening programme:

1. the accepted standards of the confidentiality of medical information should be followed as far as possible;
2. where the application of such standards might result in grave damage to the interests of other family members, the health professionals should seek to persuade the individual, if persuasion is necessary, to allow the disclosure of the genetic information. That task would be eased if it were accepted...that the consequences to the family of genetic information may in some cases make it unfair to confine the information gained solely to the individual who has been screened;
3. in exceptional circumstances, health professionals might be justified in disclosing genetic information to other family members despite an individual's desire for confidentiality".²⁶

This is an important area of concern. In our view the Department of Health, with health authorities and the appropriate professional bodies, should consider effective arrangements for the preservation of confidentiality, particularly in relation to genetic registers, and should issue the necessary guidance.

3.7.2.3 Employment
The recommendations of the Nuffield Council on Bioethics are endorsed, which propose that genetic screening programmes in the employment context be permitted only where the programme is approved by the appropriate regulatory body, where steps have been taken to ensure that individuals are not unfairly treated, where procedures are in place to assist the individual to find other employment, and where:

1. "there is strong evidence of a clear connection between the working environment and the development of the condition for which the screening is conducted;
2. the condition is one which seriously endangers the health of the employee, or is one in which an affected employee is likely to present a serious danger to third parties;
3. the condition is one that cannot be eliminated or made less hazardous by reasonable measures taken by the employer to modify or respond to the environmental risks."²⁶

3.7.2.4 Insurance
It is recommended that insurance companies should adhere to their current policy of not requiring genetic tests as a prerequisite to granting insurance.

In the light of the arguments set out above, it is recommended that there should be early discussions between the State and the insurance industry about the future use of genetic data. Pending the outcome, the companies should accept a moratorium on disclosure of genetic data. There should, however, be two exceptions:

1. in the case of individuals with a known family history of genetic disease that can be established by the conventional questions about proposers' families, individuals may be asked to disclose the results of relevant genetic tests;
2. the moratorium should apply only to policies of moderate value. The limit would be a matter to be settled between the State and the industry in the context of arranging the moratorium.

3.7.2.5 Children
The following recommendations of The American Society of Human Genetics and the American College of Medical Genetics Report35 in respect of family involvement in decision-making are endorsed:

1. education and counselling for the parents and the child, according to maturity, should precede genetic testing;
2. the provider should obtain the permission of the parents and either the assent of the child or the consent of the adolescent;
3. the provider is obliged to advocate on behalf of the child when he or she considers a genetic test to be - or not to be - in the best interests of the child;
4. a request by a competent adolescent for the results of a genetic test should be given priority over the parents' requests to withhold information.

3.7.3 Cloning

3.7.3.1 Therapeutic cloning
It is recommended that, at present, the use and derivation of human stem cells should be limited to two sources: cadaveric fetal tissue and 'surplus' embryos remaining after infertility treatments.

It is also recommended that the following principles drawn from the recommendations of the US National Bioethics Advisory Committee³⁶ should regulate the donation of human embryos for stem cell research.

1. Prospective donors should be given timely, relevant and appropriate information to make informed and voluntary decisions regarding the donation of the embryos.
2. Embryos and cadaveric fetal tissue should under no circumstances be bought or sold.

With regard to the growth of entire organs, it is recommended that this technique should be more thoroughly investigated in animal systems before experimentation with human tissue is permitted.

3.7.3.2 Reproductive cloning
It is recommended that in the use of nuclear transfer the reproductive needs of an individual should not over-ride the best interests of the child produced.

The risk attached to the use of the technique on humans carries the possibility of hormonal manipulation in the egg donor, multiple miscarriages in the birth mother, and severe developmental abnormalities in any resulting child. The potential harms outweigh the potential benefits, and until studies in animal systems reverse this circumstance, we recommend that the use of human nuclear transfer cloning to create a new life should be prohibited.

Critics have raised questions about the appropriate use of scarce resources. This is particularly important in South Africa where public policy has determined that the extension of primary health care to all South Africans must be the nation's first priority in the field of medical care. Is research into, and the practice of cloning, responsible use of limited State resources? The answer must be negative.

3.7.4 Expert supervisory body
It is acknowledged that continuing supervision of research related to cloning is necessary. At present there is no single existing body constituted for this task. Therefore, it is recommended that a new expert supervisory body be established.

In line with this recommendation for a supervisory body for gene therapy, it is recommended that this supervisory body should be of sufficient standing to command the confidence of existing Research Ethics Committees, and of the public, the professions and of Parliament. It should have a responsibility for:

1. advising on the content of proposals, including the details of protocols, for therapeutic research;
2. advising on the design and conduct of research;
3. advising on the facilities and service arrangements necessary for the proper conduct of the research.

In the light of this assessment the expert supervisory body should recommend whether or not the proposal should be approved, and on what conditions. The supervisory body should also have a responsibility for:

4. acting in co-ordination with existing Research Ethics Committees;
5. acting as a repository of up-to-date information on research in cloning, including human cloning, internationally;
6. oversight and monitoring of the research;
7. providing advice to Health Ministers, on scientific and medical developments that bear on the safety and efficacy of cloning.

It is recommended that any proposal for research related to cloning should be approved by this body as well as by a properly constituted Research Ethics Committee.

3.7.5 Patenting human genetic material
The focus of any substantive research has become profit driven, and the incentive at present is for researchers to patent sequences or partial sequences of human genes. The patenting system grants to one entity the control of all future research and medical development with respect to the subject matter of the patent, in some instances for undertaking nothing more than a mechanical procedure.⁴³ This cannot be to the public benefit, while it promotes secrecy and hinders the exchange of scientific information, resulting in duplication of efforts, inefficiency in research and greater costs to the public for access to the resultant medical products.

3.7.6 The Human Genome Diversity Project
In summary, although the stated intent of the HGDP is laudable, the evidence indicates that, in carrying out its intent, the HGDP has failed in its primary goal of bringing together the peoples of the world in an effort to eliminate prejudice, racism and xenophobia. The guidelines of the HGDP should nevertheless be strictly adhered to, in order to improve collaborative research.