1. Introduction

The cloning of Dolly the sheep at the Roslin Institute in Edinburgh in 1997, and the isolation of human embryonic stem cells by two research groups in the USA in 1998, have together opened up remarkable new possibilities in the treatment of a wide range of degenerative diseases. These may enable the creation of replacement cells to treat such incurable conditions as Parkinson's disease, heart muscle failure and diabetes. In principle, such cell replacement therapies would be greatly welcomed. For some indeed the prospect of therapies for intractable diseases is reason enough to press ahead with research into a range of possible methods. However, some of these methods also raise some serious ethical concerns over the use of embryos as a source of the cells and the use of cloning techniques.

It is important, therefore, that the ethical implications of cell replacement research and therapy are properly assessed, and used to guide which developments are pursued. In a European context, the report of the UK Government's Chief Medical Officer (the Donaldson Committee) into the potential medical uses and ethical issues of human stem cells and embryonic cloning was published in August 2000.⁽¹⁾

It is likely that other European countries will follow suit in examining these issues, each within their own legislative contexts.

The European churches are at the forefront of the ethical debate over the use of cloning and stem cell technology. The Church of Scotland in particular has an ongoing dialogue with the researchers at the Roslin Institute and elsewhere for several years. This report is a critical review of the ethical issues of human embryonic stem cells and cloned embryos. It is based on a joint submission to the Donaldson Committee,⁽²⁾

and subsequent reflections upon its report, by the Society, Religion and Technology Project and the Board of Social Responsibility of the Church of Scotland.

There are many churches and many Christians in Europe for whom research on embryos which includes their deliberate destruction is completely unacceptable. For them, the new proposals are to be rejected for reasons of principle, to do with the status of the embryo. These reasons have been thoroughly discussed in many other places. This is a very important discussion, but our focus in this paper is a question for the countries which do currently accept some limited embryo research and for other countries in Europe and the wider world which have very little or no regulation in this field. We ask whether the new areas of research also step over a new ethical boundary, and, if so , is this a boundary which we should or should not cross ?

The starting point for this paper is inevitably the UK situation, because that is where many of the relevant scientific discoveries have occurred, and because the UK government has also taken the first initiative in the world in framing legislative proposals about this research. The UK churches are also at the forefront of the ethical debate. Inevitably, several of the examples cited therefore reflect a UK situation, but it seems very likely that similar discussions will follow in other European countries. There will of course be detailed differences in each national situation, but nonetheless we believe that the broad ethical discussion will probably focus on similar questions.

A discussion on therapeutic uses of cloning and embryonic stem cells has already started within the Working Group on Bioethics and Biotechnology of the Church and Society Commission of the Conference of European Churches. The present document is the result of a first stage in this discussion. We know further reflection is required, given the complexity of the issue, the values at stake, the urgent need for the widest possible debate in Europe in a way understandable for the public, without oversimplifying things, and last but not least the necessity to resist the pressure to go ahead as quickly as possible in this utmost sensitive field, as underlined in chapter 4. Conclusions and Public Debate.

2. Scientific Aspects

Many human diseases involve irreversible cell degeneration, including Parkinson's, some heart failure conditions, leukaemia and diabetes. If a method could be found to create intact human cells and inject these into a patient, it might allieviate or even arrest the progress of such diseases. It is a very long way off technically, but studies in mice suggest that it might one day be possible.

Embryonic stem cells are special cells which exist just before the embryo begins to differentiate. At this point they have the potential to form any type of cell in the human body, and they can also be kept in the laboratory in a cell culture for very long periods. In November 1998, after many years of searching, these were isolated for the first time. In principle, you could now take a human embryo, extract these cells, and chemically direct them into becoming any particular type of human cell - skin, heart, nerve cells and so on. Certain tissues in adults also produce stem cells, which could also be reprogrammed, but so far they seem much more limited in which cell types they can produce.

The main source of embryos would be those unused after in vitro fertilisation treatments. By definition, these would be of a different genetic type to the patient, and would risk being rejected as foreign tissue. The nuclear transfer cloning technique used to create Dolly the sheep may offer a way to solve this. Blood or skin cells could be taken from, say, a Parkinson's patient and fused with a donated human egg whose cell nucleus had been removed. This would create a temporary cloned human embryo which is the genetic copy of the patient. This would not be implanted to create a cloned baby, but would be used instead as a source of embryonic stem cells. These would be directed into becoming nerve cells of the patient's own genetic composition, which ought to be less likely to be rejected.

The Donaldson Report recommends extending the limited research on human embryos which is permitted in the UK to allow them to be uses as a source of stem cells. It also calls for research into the creation of cloned human embryos which would be reprogrammed to make replacement body cells for a wide range of degenerative diseases. It proposes research into mitochondrial disease using parts of the cloning technique.

3. Ethical Aspects

The main ethical issues to consider are:

1. Is it acceptable to re-programme a human embryo so that instead of producing a baby, it develops only into certain types of cells?

2. Having decided that the reproductive cloning of human beings is unacceptable, is it permissible to use nuclear transfer procedures to create cloned human embryos for the sole purpose of producing human stem cells?

3. In either case, are there likely to be viable alternative therapeutic methods, which could avoid using embryos?

4. If the route to such alternative methods involved some limited embryo research, would such research be permissible?

5. Would it be acceptable to perform the nuclear transfer of human cells into the denucleated egg of a cow, to produce a non-viable chimera which would be reprogrammed to produce certain human cells?

6. Would the risks involved in cell replacement therapy be considered acceptable?

We note that there might be little or no need for embryo stem cells if adult stem cells prove to be more widely reprogrammable than is presently believed to be the case. This is certainly an option to be given the highest research priority. The following discussion, however, necessarily takes as its starting point the current scientific understanding that it cannot be presumed that adult stem cells would be universally productive in this way. Indeed, a number of researchers suggest that different diseases may require different routes for producing the relevant replacement cells. On present evidence, these would probably inevitably involve some use of embryos.

i. The Status of the Human Embryo

The intent of the research is to the possibility of treating extremely serious diseases in another human being. To find treatments for diseases like Parkinson's and diabetes would be a very desirable outcome. This is not sufficient cause to justify the application automatically, without first assessing the intrinsic issues of the use of the embryo that would be involved in the proposed research and therapies. Thus, before evaluating the consequences of embryo use, there is a prior question which must be asked. Is the proposed research something we should not be doing to the embryo itself, no matter what diseases were to be treated?

We rightly recoil at the idea of killing a human being in order to provide spare parts or cells for another. Should we use an early embryo to provide the cells? National legislations and perspectives vary across Europe, reflecting the deep ethical conflicts which exists about the nature of the embryo. This conflict may be summarised approximately as beliefs at two opposite poles and various intermediate viewpoints.

One extreme sees the early embryo as a ball of cells and nothing more. Because it is undeveloped and would not survive out of the womb, research on human embryos is permissible, and they may also be used routinely as a source of stem cells. The potential medical consequences wholly justify the action.

The other pole is that from conception onwards the embryo has the status of humanity, allowing no research or use that was not for the benefit of that particular embryo. This rejects any technology that involves creating dispensable embryos, including the provision of replacement cells. Many Christians take the view that once God creates life, even in embryo, it is not for humans to destroy it. This is a matter of principle, regardless of the application. Those holding this position would advocate only the use of stem cells or replacement which were derived from adult tissue. Any use which involved embryos would be ethically impermissible.

An example of an intermediate position is that of the Church of Scotland General Assembly, which considered a range of embryological issues in 1995.⁽³⁾ It affirmed the sanctity of the human embryo from conception but granted that there were limited circumstances under which such research might reluctantly be allowed prior to the "primitive streak" stage, bearing in mind the seriousness of certain medical conditions. These were primarily seen as infertility and genetically transmitted diseases. The question posed to such an intermediate position is this. Does the proposed embryonic stem cell research and cell replacement therapy fall within existing ethical categories or does it represent an ethical step change in the use of the embryo?

To the extent that this position may allow embryo research for some limited purposes, a measure of instrumentality towards the embryo has been accepted. The question is then whether this constitutes an allowance for all instrumental uses, or only some. However, taking the applications currently allowed in the UK context as an example, it may be argued that in most of these the embryo is being treated as an entity in itself. The difference with the proposed new research is that it seems to reduce the embryo to becoming a mere resource from which convenient parts, in this case cells, are taken.

It might be said that an early embryo is potentially all the cells of the human body, and therefore one is not destroying it, but merely directing it to become certain cells and not others. The concern, however, is that by the same token the embryo is prevented from developing in its normal complete fashion. By forcing the embryo to become only a certain type of cell, it is prevented from becoming all the cells as a whole. It is not "taking a cutting" from the embryo, but completely reprogramming it. This would be a profound ethical change in what is considered right about the embryo. It would drive the present ambiguity of the intermediate position over the status of the embryo down the side of being a "ball of cells". It would drive it much further away from its connection with a delivered baby

The current UK legislation upholds a principle from the 1984 Warnock Report that the embryo should be accorded "a special status". ⁽⁴⁾ Although the notion was ill defined, it is hard to see how the embryo would retain any "special status" if it is now merely a convenient resource for replacement cells. The new proposals would seem to go a significant step further in treating the early embryo only as a means to an end.

Thus we conclude that what is envisaged would be a profound ethical change in what is considered right about the embryo. To allow the use of embryos for this purpose therefore would need to follow a purely utilitarian argument. This is indeed what the Donaldson report ultimately does. It asserts that it is "not lacking in respect" towards the moral status of the embryo, provided they are used to secure benefits to human health. It suggests that if the potential benefit of treating terminal illness is arguably greater than treating infertility, then the new proposals could actually confer a greater respect for the embryo because of the nobler purpose for which it is being used (4.10). This argument sees the embryo just as a means to an end, but now sees greater potential ends from the same means.

However, in 1998 a UK Ministry of Agriculture report into animal cloning stresses that animals have intrinsic value. While we may use them for many purposes, some uses should never be allowed. ⁽⁵⁾ It cautioned against seeing animals "merely as means to an end". It would seem strange indeed at a time when animal experimentation is increasingly being brought into question, the use of human embryos seems to be much more acceptable. We should be cautious of treating human embryos with less respect than animals.

ii. Cloned Human Embryos

We welcome the focus away from the cloning of human beings, about which the churches were among the first to give a clear ethical basis for the near universal rejection.^{(6) (7)} It is also important to note that the development of animal cloning to date has shown a widespread pattern of problems in pregnancy, foetal abnormalities and early deaths of new born animals. This makes it quite clear that for the foreseeable future it would be criminally foolhardy to attempt to clone human beings, quite apart from the very strong ethical objections. The use of nuclear transfer cloning to create embryos of the right genetic type to produce replacement cells presents further ethical dilemmas, however, in addition to those discussed above for human embryos in general.

Firstly, it seems illogical to allow the creation of a cloned human embryo knowing full well one would have to destroy it on ethical grounds, because it was unethical to allow it to go to term to produce a cloned baby. The second objection is that this involves the deliberate creation of an embryo for other than reproductive purposes, although this is not specific to cloning. The use of "spare" embryos from fertility treatments would be a use of an embryo that would be destroyed anyway.

Thirdly, there is a gradualism argument. Once cloned human embryos were created, it would be much easier for someone misguided enough to go the next step and allow them to be implanted, or for someone rich enough to seek a clandestine "off-shore" treatment. This underlines the need for clear national laws, in those states which do not currently have them, to outlaw the practice of human cloning world wide.

The creation and use of cloned embryos should not be allowed as a general therapeutic procedure. We urge, however, that a priority should be put on nuclear transfer research which aims at avoiding use of embryos, by direct programming from one adult body tissue type to another. One could take, perhaps, a blood sample and re-programme directly into becoming, say, a set of nerve cells. This is of course even more speculative than the methods discussed above, but several routes have recently been suggested. Ethically this would remove most of the above objections.

There is also a further reason. The ethics committee of Roslin's collaborators, the Geron Biomed company, has urged that the technique should have the widest applicability and not be simply a treatment for the rich. It is very unlikely that enough human donor eggs could ever be provided to treat the millions of potential patients across Europe. It would therefore probably be essential to find a method of producing replacement cells without using embryos. On present evidence, however, this would probably be impossible without some human embryo research to work out the method. This poses a deep ethical dilemma whether a very limited and fixed number of experiments should be allowed to obtain the data necessary to avoid any such use of embryos in future. Some would reluctantly argue for very limited research for this sole purpose, but if it seemed unlikely to succeed, then it should stop, and not proceed to use embryos routinely for cell therapies.

iii. Animal-Human Hybrid Cells

One speculative means to the same end is to produce non-viable human embryos within cow's eggs. The idea would be to take a human cell and perform a nuclear transfer into a denucleated cow's egg. Passing an electric current would fuse the two and stimulate the human cell to divide as though it were a human embryo, but one which was not viable. ⁽⁸⁾ At the blastocyst stage of division, the stem cells would be removed and cultured as human somatic cells. Aside from the formidable technical problems, one would need to be quite sure that the use of a cow's egg as a host for the human cell had no adverse effect on the eventual human cell lines. It would also not solve the ethical problems. Even though it would avoid the creation of a human embryo, the mixing of human and animal genetic material at such a profound level would raise a major intrinsic ethical objection for most people, quite apart from the many risks involved.

iv. Separate Cloned Organs

The above discussion has focused on replacement cells. This seems the most likely medical application, but there has also been speculation about creating entirely separate cloned organs for donation. This is very remote indeed and seems unlikely to be practicable. The creation of separate human parts in vitro for eventual replacement of organs would also raise profound problems about the nature of a human being. A purely reductionist and utilitarian view of a human organ might see no particular significance beyond the medical benefit that might occur. A more holistic view of the human person might well find the idea repulsive. The nature of the animal experimentation that might be involved may also raise insuperable ethical objections. The creation of a headless frog has been cited as indicating a possible line of research. ⁽⁹⁾ Such intervention in an animal should certainly be ruled as unethical under any circumstances. ⁽¹⁰⁾ This is admittedly an extreme example, but indicates that serious questions could be involved even in the research.

v. Efficacy and Safety

If a course of action with profound ethical difficulties were to be pursued, it is also essential to be honest about its chances of success. There is a formidable list of experimental hurdles to overcome. No one knows how successful cloned cells would be on patients, nor what risk there is of cultured cells becoming cancerous, as the New Scientist pointed out. ⁽¹¹⁾ There is a risk of raising expectations too high among those suffering from the relevant diseases.

4. Conclusions and Public Debate

We have outlined a serious set of ethical objections to the extension of embryo research that would merely use embryos as sources of replacement cells. For those opposed to embryo research in principle, the objection is total. For more intermediate positions, it would overbalance the current ethical compromise in some countries like the UK to a situation where the embryo no longer had special status in any meaningful sense, and was simply regarded as a means to an end. Valid questions might also be asked whether we would be regarding animals with a higher intrinsic respect than human embryos. Further ethical problems are found if nuclear transfer cloning is used to create of embryos of compatible genetic type for producing replacement cells. The sum of these concerns is to point to a focus on research towards cell replacement methods which avoid using embryos.

These are contentious issues, and there will be a range of views within our own churches as in European people as a whole. Understandably for such new scientific developments, there is little knowledge among the general public about stem cells, as well as confusion wherever the word "cloning" is used. Several UK surveys have indicated that while members of the public were relatively clear in their opposition to reproductive cloning, they were very confused in their understanding of stem cells and non-reproductive cloning. In our discussions with lay people inside and outside the churches, it appears that few understand the technology. There is therefore a clear need for a wide public debate in civil society in Europe. These issues should not be left to closed discussion among expert committees, or hurried votes by parliamentarians, most of whom may currently know little more than the average member of the public. We therefore urge that, before legislating on the particular issues of stem cell and cloning for cell replacement therapy, a wide programme of public debate is undertaken in Europe.

We are aware of the pressure from the scientific and medical communities to press ahead, in order not to delay therapies or to lose opportunities to other countries, but these are not the only important factors. Even in those countries which have passed laws allowing some limited uses of embryos this is not an automatic permit for all future uses that science may come up with. "Gradualism" is making big ethical changes without noticing them, by what appear to be a series of small and logical steps. If we stand back and see the progression in a wider context, does this look like one step too far? As a society we certainly need more time to discuss and to decide.

Dr Donald Bruce
SRT Project
Church of Scotland
5 September 2000

References

ⁱ Ministry of Health (2000) Stem Cell Research: Medical Progress with Responsibility, Report of the Chief Medical Officer's Expert Group (Donaldson Report), HMSO: London

ⁱⁱ Church of Scotland (1999) Submission to the Chief Medical Officer's Expert Group on Cloning(CEGC), October 1999, Society, Religion and Technology Project and the Board of Social Responsibility, Church of Scotland, Edinburgh

ⁱⁱⁱ Church of Scotland (1996) Pre-Conceived Ideas, Report of the Board of Social Responsibility to the 1996 General Assembly of the Church of Scotland, St Andrew Press: Edinburgh

^iv Ministry of Health (1984) Report of the Committee of Inquiry in Human Fertilisation and Embryology (Warnock Report), HMSO: London

^v Farm Animal Welfare Council (1998), Report on the Implications of Cloning for the Welfare of Cloned Livestock, PB 4132, Ministry of Agriculture, Fisheries and Food, London

^vi Church of Scotland (1997), "Cloning Animals and Humans", Supplementary Reports to the Church of Scotland General Assembly, May 1997, p. 36/22, and Board of National Mission deliverances 35 and 36, p.16

^vii EECCS (1996) Cloning, European Ecumencial Commission for Church and Society, Brussels

^viii Cohen, P. (1998) Organs without Donors, New Scientist, 14 November 1998, p.6

^ix Sunday Times (1997), Headless frog opens way for human organ factory, London, 19 October 1997

^x Ministry of Agriculture, Fisheries and Food (1995) Report of the Committee to consider the Ethical Implications of Emerging Technologies in the Breeding of Farm Animals, (Banner Report), HMSO: London

^xi Cohen, P. (1986) Hold the Champagne, New Scientist, 14 November 1998, p.6