3. Ethics in genetic research and practice

3.4 Introduction to cloning

3.4.1 Science and morality - whose viewpoint?
Setting down guidelines for the research and practice of cloning is uncontroversial only in an environment where the analysis presented fundamentally reflects the norms of the community. The difficulty in a pluralistic community is to determine which set of values to uphold. To a large extent in the scientific community, the excitement of discovery, new techniques and the unfolding potential for scientific advancement may often be more persuasive than moral concerns. On the other hand, a society that is not permissive of innovation must stagnate. It is with a deep-seated respect for both the potency of scientific advancement and the value of human life that we engage with the ethics of cloning.

3.4.2 Techniques of cloning
The term 'clone' is used in its strictest sense to mean a precise genetic copy of a life- form. There are established cloning technologies in horticulture and the simpler invertebrate species, and the cloning of human and animal genes has been practised for decades.³⁶ Cloning at the molecular level involves the copying of DNA fragments containing genes that are amplified in a host cell. This results in large quantities of identical DNA, useful for scientific experiments. Cellular cloning, on the other hand, is the copying of somatic cells through growing in culture.

This form of cloning is sometimes used to test and produce new medical products.³⁶ The third form of cloning is directed at the reproduction of genetically identical animals, and can be divided into two distinct processes, blastomere separation and nuclear transplant cloning. In blastomere separation the developing embryo is split soon after fertilisation, when it is composed of from two to eight cells. Each cell, called a blastomere, is totipotent and is genetically identical to the other blastomeres. Nuclear transplantation cloning involves a more sophisticated technique. The nucleus of a somatic cell is placed into an egg, the nucleus of which has been removed. This technique permits asexual replication; the ability to predetermine the genetic make-up of a human being and the ability to create many genetically identical offspring.³⁶ See Section 39A of the Human Tissue Act, No. 65 of 1983, which seems to prohibit the genetic manipulation of gametes and zygotes outside the human body in South Africa and therefore applies to this type of cloning if there is any intention of implanting the zygote. (It is not clear if experimentation on the zygote or pre-embryo would be permitted so long as implantation would not follow.)

3.4.3 Cloning and genetic research

3.4.3.1 Informed consent of donors
Informed consent must be given prior to the donation of oocytes, spermatozoa, normal but 'surplus' fresh or frozen embryos, non-viable or abnormal embryos, abnormally fertilised eggs, and eggs and sperm used to generate embryos for the purposes of scientific research.

3.4.3.2 Research using human tissues and embryos
A human embryo is special because of its potential for human life. The recognition of this potential has traditionally limited experimentation on human embryos, regardless of the legal determinations of when life begins.

The most controversial research using human tissue at present, is that on stem cells derived from human embryos and fetuses. Stem cells are undifferentiated cells found in the embryo and which have the ability to develop into any specific adult cell required in the body,³⁷ although there are many different types of stem cells. As a general rule, all have the ability to divide and self-renew and to commit to a more specialised function. For research purposes it is important to distinguish between two forms of stem cells. Totipotent stem cells have the ability to form an entirely independent human being if placed in utero, and they are found in an embryo which is at the 16-cell stage. Pluripotent stem cells have the lesser ability to give rise to any type of specialised cell and they are found within the inner cell mass of a blastocyst.³⁸

There is no controversy over research involving the use of totipotent cells - it is not permitted. However, the ability of pluripotent stem cells to develop into any specified tissue cell makes them extraordinarily interesting to study. Theory suggests that pluripotent stem cells could be cultured to provide an unlimited source of specified cells under the right condition, and the research of Gearhartl and Thomsonm on stem cells has confirmed this.39 Potential medical applications include the treatment of cell-based diseases and the development of human organs for transplant purposes. The creation of human tissue cultures may even eliminate the need for animal and human trials of medical products. Despite the obvious usefulness of the research we must ask at what point we are willing to let theory remain just that.

There are several objections that must be addressed. The first is that current research involves the use of stem cells derived from human embryos. The current sources are:

1. human fetal tissue following an elective abortion;
2. human embryos created by in vitro fertilisation and no longer required;
3. human embryos created by IVF with gametes donated for the sole purpose of providing research materials; and
4. embryos generated asexually by somatic cell nuclear transfer or similar cloning techniques.⁴⁰

The fact that the source is a human embryo is itself problematic, not because of sentimentality associated with research involving human tissue (using human tissue derived from donated cadavers is not controversial) but because the extraction of stem cells from the human embryo eliminates that embryo's potential for life. It is not possible to completely rationalise this response. However, the objection must be treated with respect as the genuine response of a portion of the population, which believes that the right to life and dignity is applicable to human embryos. It does not help to enter into a legal debate as to when the embryo acquires the status and concomitant rights of a human being. The issue is not one of legality, but of mores.

There are several arguments in favour of the use of stem cells in research, which seek to justify the use of human embryos in research. The first contends that the use of human tissue derived from embryos from in vitro fertilisation processes and legal abortions cannot be any more objectionable than either of these procedures, particularly when the embryo's potential for life has already been terminated. The use of the fetal tissue does not result in the intentional destruction of a live fetus, and the fetus is not created solely for research purposes. It is also argued that, unlike an embryo, a stem cell is not capable of forming a new, independent life. The arguments also point to the potentially extraordinary life-saving applications that, but for research, will remain outside the realm of medical practice.

There is no easy resolution of the issues involved. Ethics do not and can never mean anything so restrictive as those mores of society determined by the law. Fortunately, the research of Mackay and his colleaguesn may allow the scientific world to side step this issue altogether. The advances made by Mackay indicate that it is possible to isolate adult stem cells derived from the adult brain and spinal cord. Although these stem cells can only differentiate into any of the three major cell types in the brain and spinal cord, there is hope that the isolation of other adult stem cells will obviate the need for research on human embryos. It is impossible to come to a clever compromise, and clarity about the status of such research is essential.

It is recommended that, for the present, the use and derivation of human stem cells should be limited to two sources, cadaveric fetal tissue and embryos remaining after infertility treatments. Some good should come from these embryos rather than that they are totally wasted.

It is also recommended that the following principles, drawn from the recommendations of the United States National Bioethics Advisory Committee,³⁶ 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.

3.4.4 Cloning and genetic practice

3.4.4.1 Reproductive cloning and cloning as a biogenetic tool for therapeutic purposes

3.4.4.1.1 Potential applications of cloning

3.4.4.1.1.1 Therapeutic cloning
The generation and harvesting of human tissue to satisfy the therapeutic needs of humans requires careful consideration. In principle, the application of nuclear transfer cloning could provide a host of embryos with a potential source of organs or tissues of a predetermined genetic background, namely those of the donor of the nucleus. This notion, however, elicits horror from most scientists, and undermines the human dignity afforded by Section 10 of the Constitution. It devalues the potential life element of all human embryos and prioritises the needs of a living individual over the potential life of the embryo. An embryo is being created and allowed to develop to a stage where it would be a source of 'spare parts' for the donor of the nucleus. This practice cannot be equated with abortion, where the potential life of the embryo is terminated at a woman's choice, because the reason for the creation of that embryo, and the reasons for the termination of its potential life are fundamentally different.

A more acceptable approach could be the development of specific tissue rather than an entire individual. The growth of entire organs would revolutionise organ transplantation. However, this technique should be more thoroughly investigated in animal systems before experimentation with human tissue is permitted.

Another application is the transplantation of cells or tissues from totipotent embryonic stem cells. This would not require the generation and birth of a cloned individual for cell-based applications. "It might be possible to take a cell from an early blastomere and treat it in such a manner as to direct its differentiation along a specific path. By this procedure it might be possible to generate in the laboratory sufficient numbers of specialised cells, for example bone marrow stem cells, liver cells or pancreatic pan beta cells (which produce insulin) for transplantation. If even a single tissue type could be generated from early embryonic cells by these methods and used clinically, it would constitute a major advance in transplantation medicine by providing cells that are genetically identical to the recipient."³⁶ The possible use of nuclear transfer cloning to create human embryos, as stem cell 'cultures' for the purpose of growing specified cells for transplantation, is controversial in the extreme. Two immediate concerns are raised: first, that human life is generated as a means to an end and terminated just as easily; and second, the use of the cells of early embryos for the nuclear transfer cloning.

Understanding that there are many approaches to the creation of specific stem cells, it is recommended that this research be conducted in a manner that eliminates the need for the use of human embryos. A more acceptable approach might be the development of specific tissue rather than an entire individual. The growth of entire organs would revolutionise organ transplantation, but this technique should be more thoroughly investigated in animal systems before experimentation with human tissue is permitted.

3.4.4.1.1.2 Reproductive cloning
Cloning is also a technique that, potentially, can be used in assisted reproduction, for the purposes of enhancing the reproductive potential of a human being. This form of cloning gives effect to the right of every individual to make choices regarding their own reproduction, a right entrenched in Section 2(z)(a) of the Constitution. Reproductive freedom includes not only the right to choose not to reproduce, or to terminate a pregnancy, but also the right to choose how to reproduce. Assisted reproductive technology is widely used and accepted, although in most situations of assisted reproduction, the cells are manipulated only to realise the union of the gametes. The strongest case for permitting the use of nuclear transfer cloning is where this potential application is a necessary means for procreation by that individual.

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.

3.4.4.1.2 Safety
There are important risks associated with current cloning technology, to which a cloned embryo would be exposed. These risks are potentially harmful and even life threatening to the embryo, and there can be no justification for experimenting with human embryos in these circumstances. If cloning techniques become so refined that there is no risk to a human embryo, it will become necessary to undertake a comprehensive investigation of the psychological impact of cloning on the child, the family and society. It may be possible to identify harms, such as a diminished sense of individuality and personal autonomy (although naturally produced identical twins would deny that there are harms suffered or experienced by them on this score), and the potential for discrimination, which a cloned child may suffer. Every effort must be made to alleviate these concerns before cloning is permissible as an assisted reproductive technique. Further, the circumstances in which cloning may be permissible must be enumerated. It would be unethical to permit clones for commercial or other purposes unrelated to medical necessity.

A further cause for concern is the creation of multiple embryos, which may not become viable, for the creation of one viable cloned embryo. In many respects this issue has been addressed by the techniques and practices used in in vitro fertilisation, and will not be recapitulated here.

It is arguable that the freedom of scientific enquiry must allow and encourage research and scientific advances. However, although the freedom of scientific research and academic freedom are enshrined in Section 16(1)(d) of the Constitution, that right itself must be balanced against the other rights in the Constitution. Thus, constraints on the freedom of scientific enquiry may be imposed to protect the safety of the community and individuals, and the rights and interests of the subjects of scientific enquiry.

At present there are compelling reasons to limit the inquiry into human nuclear transfer cloning. We believe that there is no scientific justification for experimenting with a human embryo that has the potential to become a human being. There are considerable risks involved in successful somatic cell nuclear transfer cloning, which we believe make it unacceptable for use in experimentation with human embryos. For instance, the technique that produced Dolly was successful in only 1 of 277 attempts, and it is not even clear whether Dolly's life expectancy will be reduced.

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 possible severe developmental abnormalities in any resulting child. The potential harms outweigh the potential benefits, and until studies in animal systems reverse this circumstance, it is recommended that the use of human nuclear transfer cloning to create a new life should be prohibited.

3.4.4.2 Fears and critique of nuclear transfer cloning
The greatest fears regarding cloning are in respect of its impact on the psyche of the cloned child, the manner in which the child will be nurtured in society, and the moral, religious and cultural values of that society. The strength of public reaction to cloning reflects a deep concern that important social values will be harmed if cloning is widely used.

Further, it has been argued that there exists a moral right to a unique identity, including a genetic identity, which cannot be permitted to be undermined, for to do so would lead to a diminishment in physical individuality and psychological autonomy - a right extended to all human beings under the protection of human dignity in the Constitution. Some ethicists disagree, arguing that cloned individuals are not more closely related genetically to the donors of the nuclei which gave rise to them than are natural identical twins.

However, it must be noted in this regard that the physical and psychological traits of individuals are not determined by genes alone. Each individual is a result of a complex interaction between his or her genetic make-up and the environment in which she or he develops.

One of the many fears surrounding nuclear transfer cloning is that it may become a form of eugenics, whereby certain human traits valued in society are effectively reproduced by those who have the financial means, thereby creating class structures based on wealth and genetic make-up. The genetic manipulation required to develop only those traits identified as positive human traits, in a cloned embryo, must be treated with the same caution outlined in the discussion of eugenics under the topic of gene therapy.

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. A decision on whether research into, and the practice of cloning, are a responsible use of limited State resources must be made.

3.4.5 Regulation of cloning research

3.4.5.1 Expert supervisory body
It is recommended that continuing supervision of research into and related to cloning is necessary. At present there is no single body constituted for these tasks. Therefore, it is recommended that a new expert supervisory body be established.

In line with the recommendations 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, 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 the 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 make a recommendation on whether 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 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 be approved by this body as well as by a properly constituted Research Ethics Committee.