Human 'cloning' : a discussion paper for the World Medical Association
October 1999
Other uses of 'cloning' technology
The second category of activities to be considered are those which use the same or very similar techniques as reproductive cloning but where there is no intention to bring into existence genetically identical individuals. The procedures considered in this section aim to cure or avoid illness and disability or to further basic biological research. These procedures are sometimes included within a broad heading of 'cloning' although the aims and the outcomes are fundamentally different from those of reproductive cloning.
Production of tissues for transplantation
A proposed future use of cell nuclear replacement technology is to develop compatible tissue for transplantation to those with tissue or organ damage caused by injury or disease. Currently, recipients of donated organs or tissue are required to take powerful immunosuppressive drugs, the long-term use of which leads to increased susceptibility to infection and cancer. In the future, various types of tissue, compatible to the individual patient, could be generated using cell nuclear replacement technology. The nucleus would be transferred from one of the patient's own somatic cells into an enucleated donor egg. As with reproductive cloning, the egg would then be stimulated to begin cell-division but it would be allowed to develop only to the stage needed to separate and culture embryonic stem cells. The embryo would not, at any stage, be transferred to a woman's uterus for gestation. When separated, the embryonic stem cells have not begun to differentiate but, given the appropriate circumstances, it is anticipated that they could be stimulated to differentiate into whatever type of tissue was needed - neural tissue for the treatment of degenerative diseases such as Parkinsons disease, bone marrow for leukaemia sufferers, islet cells for diabetes, muscle tissue for the repair of a damaged heart or skin for treating burns victims. Not only would this overcome problems of the shortage of tissue and organs available for transplantation but also, because the cells were generated using the patient's own DNA and so would be fully compatible, there would be no need for the use of immunosuppressive drugs. Some newspaper reports have, perhaps over-optimistically, predicted the growth of whole organs for transplantation using this method ('Scientists to grow a human heart', Sunday Times, 11 October 1998). Whilst this is most unlikely to be feasible, it is very possible that a damaged organ could be repaired using compatible tissue where currently a replacement organ would be required.
Two main objections have been voiced to the development of this technology. Some people have a fundamental objection to all embryo research and, regardless of the potential benefit, would not sanction the use of human embryos for such purposes. This opposition is often based on the belief that life begins at conception and that, from that stage onwards, the embryo deserves the same protection and respect as any other human being (Although in the case of cloning there is no 'conception' - usually taken to mean the unification of sperm and egg - once an embryo has been produced which has the potential for development given the right circumstances, it is likely that this would be perceived as the same as an embryo produced through conventional methods). For those who hold this belief, the use of cell-nuclear replacement in this way involves the bringing into existence of a human being with the specific intention of destroying it, which cannot be justified regardless of the scale of potential benefit. But this view of the status of the embryo is not one which is universally shared. Another approach is to acknowledge the potential of the embryo, given the right circumstances, to develop into a fetus, child and adult and thus to afford it some, but not absolute, respect and protection. This is the approach favoured in the United Kingdom following nearly a decade of debate culminating in the Human Fertilisation and Embryology Act in 1990. For those who follow the latter approach, the very large number of people who could potentially derive great benefit from the development of this technology is likely to be very persuasive. If embryo research is permitted for promoting advances in the treatment of infertility or to develop effective techniques of contraception or to increase knowledge about the causes of congenital disease, why should it not be permitted to develop methods of developing compatible tissue for transplantation?
It would be wrong to imply, however, that it is only those who fundamentally oppose all embryo research who have concerns about the use of cell nuclear replacement for this purpose. In the course of developing embryonic stem cells, an embryo is produced which has the same nuclear DNA as the nucleus donor and has the potential, given the right circumstances, to develop into an adult. Some people have an innate suspicion of scientists which leads them to presuppose that if something is possible, the temptation to resist will be too great. How can society be sure that the line is not crossed and that scientists will be able to resist the temptation of implanting a cloned embryo? Regulation could be established imposing severe penalties on those acting outside the defined parameters but some people vehemently argue that most, if not all, slopes are slippery and that once something is permitted a gradual shifting of barriers is inevitable. Others take the view that efforts should focus on preventing abuses rather than preventing the development of potentially beneficial techniques. This brings us back to the debate, well-rehearsed in embryo research, about whether regulation or prohibition is more effective in preventing abuse.
Avoiding mitochondrial diseases
Another potential therapeutic use of cell nuclear replacement would be for the avoidance of mitochondrial diseases. Although it uses the same cell nuclear replacement technique as reproductive cloning, there is no possibility of bringing into existence genetically identical individuals. As this technique has sometimes been included within a broad definition of 'cloning', however, it is briefly discussed here.
Mitochondrial diseases are severe, life-threatening disorders which are caused by defects in the mitochondria which are found in the cytoplasm of each cell. If a woman has the disease herself, all of her egg cells will carry some of the defective mitochondria and thus, all of her children may be affected. It has been suggested that the nucleus could be removed from the woman's egg and placed into an enucleated donor egg, before fertilisation, in order to avoid the disease. The resulting embryo would have nuclear DNA from the woman and her partner and mitochondrial DNA from the egg donor. It would not have the same DNA as any other embryo or any other individual, so would not be a clone.
Pre-implantation genetic diagnosis
Preimplantation diagnosis has been included in some statements about 'cloning' (For example, the European Parliament Resolution on Human Cloning, 1998 includes pre-implantation diagnosis in its definition of 'cloning of human beings') because it uses similar techniques to those used in embryo splitting (see above) even though there is no possibility of bringing into existence genetically identical individuals nor any intention to do so. Preimplantation genetic diagnosis involves the fertilisation of oocytes in vitro and the removal of one or two cells from each embryo to be tested for the genetic disorder for which there is a known familial risk. These cells are not totipotent, ie. they could not give rise to a new individual. The rest of the embryo continues to develop normally and those which do not carry the disorder are selected for replacement into the uterus for gestation. This technique, which was first successfully used in 1990, allows a woman to begin a pregnancy knowing that the child will not suffer from the disorder for which there is a known risk. Its use is limited by the very specialised expertise required and the invasiveness and relatively low success rates of in vitro fertilisation. For those who are known to be at risk of a severe genetic disorder, however, it provides an alternative to prenatal diagnosis followed by the termination of an affected pregnancy. Some people's opposition to prenatal diagnosis, however, is not solely linked to issues around the termination of pregnancy but is based on a fundamental objection to what they see as making advance judgements that "some people's lives are not worth living". Those who perceive prenatal diagnosis in this way are unlikely to accept preimplantation diagnosis.
Basic research
The use of what can broadly be termed 'cloning techniques' are also used for furthering basic biological research. This research does not have a direct therapeutic aim, nor does it entail the bringing into existence of a new individual, but the research is designed to increase knowledge of basic biological processes which may, indirectly, lead to improved therapies. The vast majority of this work, particularly in the early stages, will be undertaken using animal, rather than human, material.
Research is likely to lead to greater understanding of why somatic cell mutations occur which are believed to contribute to the ageing process and the development of cancers and tumours. It may lead to an understanding of how the adult nucleus can be so radically reprogrammed by the egg cytoplasm and this may render the use of eggs unnecessary for the development of compatible tissue. It could lead to greater knowledge of the role of mitochondrial DNA and basic embryonic development. It might also be possible to develop ways of reprogramming human cells to treat certain diseases and to provide insight into genetic imprinting ('Threatened bans on human cloning research could hamper research', Journal of the American Medical Association 277(13) pp 1023-1026) ( imbalance between the expression of the paternal and maternal copy of a gene can contribute to genetic disease).
With the exception of research which involves human embryos, on which views are likely to differ (see above), these areas of research are relatively uncontroversial. There is a risk, however, that their inclusion under the general term 'cloning' could lead to misplaced anxiety about their aims and objectives and, in an effort to prevent misuse of the technology, it is feared that much appropriate and beneficial basic research may also inadvertently be curtailed.