CLONING ISSUES IN REPRODUCTION, SCIENCE AND MEDICINE

CLONING ISSUES IN REPRODUCTION, SCIENCE AND MEDICINE

CLONING ISSUES IN REPRODUCTION, SCIENCE AND MEDICINE

The Royal Society of Edinburgh is pleased to respond to the consultation document issued by the HGAC and HFEA. The RSE is Scotland's premier learned society, comprising Fellows elected on the basis of their distinction, from the full range of academic disciplines, and from industry, commerce and the professions. This response is based on comments received from a small number of our Fellows with expert knowledge of this subject. However, a major caveat should preface the following response. Cloning is an emotive subject with ethical, moral and theological implications. Therefore it is not possible to provide a view which would be acceptable to all RSE Fellows. The comments that follow represent a consensus of those Fellows with expert knowledge of the science underpinning animal cloning. They do not represent a similar consensus of Fellows with a professional interest in the ethical, theological or legal aspects of the subject, yet such views and reservations should be accorded equal weight and importance, and are touched upon in some measure in this response.

Any new issues in 14 day period (paragraphs 7.3 - 7.6)

Q1 Would research using nuclear replacement technology raise any new ethical issues in relation to what is permitted in work with embryos in the 14 day period?

The distinction drawn by the Working Party between "reproductive cloning" and "therapeutic cloning" is crucial. Human reproductive cloning would be ethically unacceptable to the great majority of both the general public and the scientific community. Therapeutic cloning, which is potentially of enormous clinical benefit, should not present any new ethical concerns above those raised by in vitro fertilisation and embryo research up to 14 days.

There would, however, need to be careful consideration of the techniques and time restriction that may be required for embryo manipulations that could lead to the generation of appropriate stem cells for therapeutic purposes in the treatment of degenerative diseases and other tissue damage. There are cell types which develop only quite late in development and it is difficult to know whether cells with appropriate differentiation potential might be generated at earlier stages. For example: cerebellar degenerative conditions (ataxias) may benefit from "autologous" or cloned cerebellar cell implants, but the cerebellum develops very late in gestation and it is not clear whether such cells could ever be generated in in vitro culture, even if that is permitted beyond the 14 day period. Much animal work would be required to assess the possibilities. This does assume that the nuclear transfer procedures could be reproduced in suitable laboratory animals. As ever, there are ethical considerations, but not particular novel ones, when contemplating animal experimentation.

Q2 Are there any medical or scientific areas that might benefit from research involving human nuclear replacement?

If nuclear transfer can be achieved in humans it would create the possibility of generating
from an individual a supply of cells that could subsequently be reintroduced to that individual withoutimmunological rejection. Such cells could be used for:

  • Tissue repair, for example as a source of new skin for burn treatment
  • Cell replacement, for example to provide new blood elements for leukaemia or AIDS patients
  • Gene therapy, by providing a vehicle for delivering corrective genes, for example to treat thalassaemias or certain neurodegenerative diseases.
  • The development of tissues for smoother, more risk-free transplantation procedures

Other areas might include studies of biological issues such as ageing, control of gene expression, gene imprinting, and the interaction of cytoplasmic factors with nuclear genes. The only case in which nuclear transfer of a unique newly created nucleus into another egg cytoplasm might be acceptable would be for mitochondrial disease therapy.
In order to produce a population of cells for transplantation, nuclear transfer might be carried out from a cell of the individual into an enucleated cell which could be:

i A somatic stem cell
ii An embryonic stem cell
iii An oocyte or 1-cell embryo
iv An oocyte, followed by secondary transfer into a somatic or embryonic stem cell

There are currently no data on the feasibility of (i) or (ii) in any mammal, but the probability of success would seem low. Research in this area should not raise new ethical or legislative concerns as it does not involve the generation of a human embryo.

Nuclear transfer into an oocyte (iii and iv) is the approach to nuclear reprogramming validated by Dr Ian Wilmut and colleagues at Roslin. The therapeutic application of this method would be either to develop a cloned embryo for a limited period in vitro and then isolate embryonic stem cells, or possibly to reprogramme a nucleus in an oocyte and then transfer directly into a previously established embryonic stem cell.

The significance of producing embryonic stem cells is that they can be amplified indefinitely in culture, can be subjected to precise genetic modifications, and can be induced to differentiate into a broad range of cell types. Current research with mouse embryonic stem cells has demonstrated their utility as a source of cells for transplantation. To give one example, it has been shown that embryonic stem cell derived neurons can be transplanted into the brain where they will form specific types of neuron (Brustle et al. [1997] Proc Nati Acad Sd USA 94, pp14809-14814; Deacon et al. [1998] Exp. Neurol. 149, pp28-41). This suggests that human embryonic stem cells could provide a route to therapy for conditions such as Parkinson's, Huntington's and Alzheimer's diseases. Transplantation of ES cell derivatives could be used both for direct cell replacement and to reduce or halt loss of host cells by expression of neuroprotective factors such as neurotrophins. The only alternative sources of neurons for transplant are human foetal material from early abortuses, which raises serious ethical issues and is in any case impractical on a large scale, or xenografts, for example using pig foetal neurons, which presents safety concerns and immunological problems. Neither of these two avenues is amenable to genetic manipulation.

For isolation of embryonic stem cells, embryos are only required to develop to the blastocyst stage which falls well within the 14 day limit of current legislation. In order to incorporate nuclear cloning, however, the scope of currently permitted human embryo research would have to be broadened to encompass therapeutic applications. Such an extension to the legitimate subjects of research is perhaps justified by the prospective benefits of developing patient-specific stem cells.

Own genetic identity (paragraph 8.2)

Q3 To what extent can a person be said to have a right to an individual genetic identity?

Since naturally arising monozygotic twins exist, it is difficult to argue convincingly that there is a human right to unique genetic identity. Nevertheless, human variability is of great importance to our perception of the right for individuals to be different in an almost infinite number of ways.

There is, in addition, a very clear and important difference between having two identical twins born at the same time and brought up together (in most cases) and the prospect of producing identical individuals sequentially by reproductive nuclear transfer. Attempts to replace a lost child in such a manner would be ghoulish and psychologically very unpleasant for the person concerned, and the moral, ethical and theological arguments against any such a procedure would be convincing.

If individual humans were cloned by nuclear replacement from an adult cell they would be even more different from the donor since their mitochondria, their age, their environment and their upbringing would be different.

Instrumentalisation (paragraph 8.3-8.5)

Q4 Would the creation of a clone of a human person be an ethically unacceptable act?

In company with the majority of people, we would consider that the cloning of a human being is unethical. Clones of people by nuclear transfer present a threat to our concept of human identity and individuality through duplicating an important contribution to the uniqueness of the individual. Using these techniques has consequences for the child and society. Therapeutic cloning with possible benefits to health care should be allowed under strict supervision but the creation of human beings by this method should be prohibited.

Experimental human beings (paragraph 8.6)

Q5 Would the likely cost in terms of failures and/or malformations inevitable in developing a programme of human reproductive cloning be ethically acceptable?

The cost would be unacceptable. The production of identical human beings by deliberate human agency is unethical. However, therapeutic cloning with its possible benefits with regard to prevention and treatment of disease is acceptable, within specified safeguards.

Natural/Unnatural (paragraph 8.7)

Q6 What ethical importance might be attached to the distinction between artificial processes for which there are parallels in natural processes and those for which there are not?

There is an ethical difference between processes which occur naturally and those which do not. Because something occurs in nature does not necessarily make it acceptable to simulate this by artificial means. Identical twinning by the splitting of the fertilised egg is a natural phenomenon, but recreating that process in the laboratory is not, in our view, acceptable in humans.

Building public confidence in and understanding of new developments in genetic techniques (paragraph 9.2)

Much work remains to be done in well-controlled laboratories before routine reproductive nuclear transfer is permitted even in animals. There is much to be learned still about Dolly's characteristics. We do not yet understand nuclear ageing processes or know whether these are also fully reprogrammed. It should be made clear that even the animal work is under careful scrutiny through Home Office licensing. Perhaps these licensing procedures should be publicised more widely.

The possibilities of human cloning for transplantation and therapeutic ends should be discussed. The advantages of using "self" cells for such procedures should be spelled out clearly. Perhaps some of the existing related procedures which are quite widely accepted could be pointed out:

There are already several therapeutic techniques using in vitro production of "self" cells and tissues for implantation: such as growing large areas of self-skin in culture for auto-grafting. There are many techniques already in accepted use, which are hardly different from culture of stem cells from nucleartransfer of adult cells into an egg and development of stem cells or mixed cell tissue for transplantation etc.

Education is also needed into the processes of development, growth control and what happens when this goes wrong, so that there could be informed discussion of what problems may lie ahead.

April 1998

Further information is available from the Research Officer, Dr Marc Rands

 

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