The Royal Society of Edinburgh is pleased to respond to the Department of Health’s consultation on the Chief Medical Officer’s Expert Group on Cloning. 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 has been compiled with the assistance of a number of Fellows with experience in this area.

The paragraphs below relate to the questions posed in the covering memorandum 'Expert Advisory Group on Therapeutic Cloning in Humans" dated 2 September 1999.

Current research areas on therapeutic cloning which are the most important

There are three main areas:

Cloning animals by nuclear transfer. This is developing in a number of species, including ruminants, pigs and mice. The range of species studied should be widened as it could well be that advances are initially more easily made in one species which, with further work and more detailed experimentation, can be applied more widely to other species, including man.

Pluripotent Stem Cells (PSCs). Mouse PSCs (or embryonic cells) are routinely used in many laboratories to introduce precise genetic change into the germline. When allowed to differentiate in vivo or in vitro they are able to form many of the adult cell types, and they are useful models for early development studies, such as researching the pluripotential state and as a means of understanding the mechanisms of differentiation of specific cell types, such as neurones and blood cells.

Re-programming. Nuclei from differentiated adult cells can be re-programmed into other pathways of development. This has great potential in human medicine because the nuclei from cells of an individual could be re-programmed to make, for example, heart muscle or neuronal cells which, being "autologous", would not suffer from immune rejection. At present, re-programming adult nucleiis solely by nuclear transfer into an oocyte which is not ideal. More research into the re-programming mechanism would enable the benefits to be obtained without recourse to oocytes and thus remove not only a logistic constraint but also lessen the ethical problems inherent in working with oocytes as the starting point.

Areas of human health in which therapeutic cloning is most likely to provide benefits
The possibilities are vast, and include autoimmune diseases, ageing diseases and many inherited genetic disorders. Parkinson's disease and heart diseases are potential targets, together with sickle cell anaemias, diabetes and muscle-wasting diseases. The first priority must be diseases which affect large numbers of people world wide but, eventually, the research should be widened to rare diseases also.

Possibility of replicating animal work to humans
At present work on humans lags far behind the mouse work but it is only a matter of time, and resource availability, before work with humans catches up. The pace of research work in this area is so rapid that what may appear to be a long time at present may well transpire to be a much shorter delay than originally anticipated.

Technical problems which may arise
At present, with much of the work restricted to re-programming oocytes, the main problem is the supply of human oocytes from which to generate PSCs. It follows that one of the major problems is replacing this technique with the programming of other adult cells, as already discussed in the answer to question 1.

Safety problems
There are no obvious safety problems. The risk of transmission of infectious diseases via transplantation of cells generated in vitro will be considerably lower than using conventional tissue or organ transplants from a donor, as they will be generated under highly regulated (GMP) conditions and intensively monitored.

There could be concerns as to the effects of in vitro culture on the propensity of such cells to undergo malignant transformation, either by mutation or by epigenetic changes. Governmentally supervised regulatory controls will be required to enable these cells to be clinically used, on the same principles that have already been established for evaluating new medicines. It should be noted that autologous transplants would be advantageous because immuno-supression will not be required.

Alternatives to achieve the same ends
There are some developments in the manipulation of somatic stem cells (SSCs) derived from foetal or adult material which may prove advantageous. An example has been work endeavouring to identify haematopoietic stem cells in humans, but so far advances in this field have been limited. Nevertheless there is likely to be progress in this area in future.

Ethical issues
The main ethical issues at present are connected to the use of fertilised human oocytes. If other ways of re-programming cells, other than reproductive cells, can be found then one of the main ethical objections can be overcome.

However, it should be pointed out that under the 1990 HEFA Act, research with embryos is allowed up to the 14th day in order to overcome problems of human infertility, so it does not seem logical to impose tougher restrictions on work aimed at combating life-threatening diseases.

Until such time as alternatives to the use of oocytes are available, it may be necessary to carry out the transfer of a nucleus into a human embryo which was not foreseen in the original Act. Firstly, as a means of generating PSCs from a defined individual, for example if tissues for autologous transplantation are required, and secondly to allow a better understanding of how re-programming works in humans. It should be emphasised, however, that the eventual object of all this work is to carry out re-programming without recourse to the oocyte, and so in the long run this will reduce or eliminate the requirement for working on the most ethically sensitive of all human cells.

Consequences for health care provision
Therapeutic cloning opens up the possibility of treating a vast array of degenerative diseases, which at present are untreatable. Generally speaking, such advances should be highly cost effective, reducing the requirement for medical intervention, hospitalisation and long term chronic or terminal care.

Other comments
Cloning technology is currently at the stage where recombinant DNA technology was in the early 70's. It is revolutionising how we contemplate biology and medicine, but the technology has yet to be developed to the stage where it can deliver the proposed benefits. Like many, or most, new powerful technologies it poses a number of ethical challenges, which need to be resolved by open and informed public debate and also by the delivery of tangible benefits to Society.

Additional Information
In responding to this inquiry the Society would like to draw attention to the following Royal Society of Edinburgh responses which are of relevance to this subject: Animal Tissue into Humans (April 1997); Consent and the Law (December 1997); Cloning Issues in Reproduction, Science and Medicine (April 1998) and Review of the Common Law Provisions Relating to the Removal of Gametes and of the Consent Provisions in the Human Fertilisation and Embryology Act 1990 (April 1999).

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