Together cloning and stem cell technologies present some of the most exciting possibilities at the leading edge of biomedical research, and some of its most challenging ethical dilemmas. This article explores some of the key issues in these fields, and lays out a range of different ethical views.

What's the Church doing here?

The Church of Scotland set up the Society Religion and Technology Project in 1970 to examine the ethical & social issues of emerging technologies. Since 1993 it has run an expert working group on non-human genetic engineering, producing the book "Engineering Genesis", acclaimed as the most balanced study available on GM animals, plants and food. Professor Ian Wilmut, leader of the Roslin cloning team, was a member of the group. So when Dolly became a global issue, SRT was in a unique position to offer informed ethical comment to the world, and has continued in the forefront of the international debate on cloning and related issues. The Church of Scotland General Assembly voted against human reproductive cloning in 1997 but for some therapeutic uses in human medicine in 2001.

Reproductive Cloning

When Dolly was announced in early 1997, the media and governments alike immediately focused on whether the same techniques might be used to clone people. Speculative as the idea is, various people have attracted a lot of publicity for themselves in claiming they would soon produce a cloned baby. So far this has not happened, and most people agree that it would be wrong for several reasons.

Most animal cloning has had persistent and unpredictable welfare problems during pregnancy and soon after birth. These are sufficient for the Ministry of Agriculture's Farm Animal Welfare Council to call for a moratorium on commercial animal cloning.

It would be irresponsibly risky to try a faulty technique on humans. Cloning would be more likely to produce a dead or deformed baby than a healthy one.

There are also relationship and psychological risks. How would it feel to know you were made to be the deliberate genetic copy of your dad or mum, or to bring up a child which you knew was your own clone?

But, above all, it's a question of principle. Cloning is an act of control, not just of a gene or two, but over someone else's complete genetic make-up. If an embryo splits into identical twins, it's a random event, which no one planned. The genetic make-up of that embryo was also unknown and unique. Cloning would take the genes of someone you already know and deliberately create another person to have exactly the same genetic composition. It is an act of control that no human being should make upon another. It's also irreversible. We can accept or reject any other influences our parents and others seek to make upon us, but we cannot change our genes. Of course, human beings are much more than just genes, but our genes are pretty important! Thus we may argue that the human reproductive uses of cloning technology are both ethically and pragmatically off limits.

Stem Cells and Therapeutic uses of Cloning

The main focus has moved from speculating about cloned humans to researching the use of nuclear transfer cloning for treating degenerative diseases, in conjunction with the new science of human stem cells. Embryonic stem cells are cells derived from a very early embryo which have the capacity to become any cell type. They can now be isolated and replicated indefinitely in the laboratory. Scientists hope they can be reprogrammed to become any cell type of the body. These could then be used to replace lost cells in a wide range of degenerative diseases.

If the source was a spare IVF embryo, the cells would not be of the same genetic type as the patient. For nerve cells for Parkinson's patients, this is not a problem, but for heart muscle cells or diabetes treatments, there could be a serious risk of cell rejection by the body. One way round this could be to use the Dolly technique to clone a human embryo from a skin sample of the patient, as the source of the stem cells, which would then be of their own genetic type.

Such applications are a long way from being practicable, but they raise different and equally searching ethical questions, about the source of the cells and the status of the embryo, whether cloned or not. These were the subject of a series of parliamentary debates, and a free vote of MPs in December 2000 and the House of Lords in January 2001.

What is an Embryo, ethically?

The idea of using human embryos for cell replacement therapies raises afresh the deep ethical conflicts about the nature of the embryo. These were widely discussed in debates leading up to the Human Fertilisation and Embryology Act of 1990. Back then the main issue was embryo research for reproduction and fertility. Now the focus is on using embryos as a source of cells and this poses some old and some new questions.

There are three main views of the early embryo. One extreme sees it as just a ball of cells and nothing more. It could not survive out of the womb, and has no feelings or consciousness. Reproductive and stem cell uses of embryos are equally permissible.

At the other end of the spectrum, the embryo must be accorded the status of humanity from conception onwards. This would allow no research, whether for reproduction or stem cells, that was not for the benefit of that particular embryo. It rejects any technology that involves creating dispensable embryos. Some in the churches take that view, but by no means all.

For these two viewpoints embryonic stem cells raised no new issue, and the answer was quite clear. Many people take an intermediate view, however, for example, seeing the embryo as having potential or emergent human status, demanding respect, but not the full status accorded to a baby. The 1990 Act reflects the Warnock Report's compromise view that the embryo should be accorded a "special status", but less than a full human person.

In 1995 the Church of Scotland General Assembly considered a range of embryological issues. It affirmed the sanctity of the human embryo from conception, but it also 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. This roughly accorded with the present 1990 Act.

Is it Unethical to Use Human Embryos for Cell Replacement?

Some like the Government's Donaldson Committee saw the issue primarily in consequential terms. Having once allowed some embryo research means the principle of any embryo research is accepted. It implied that a use that could lead to therapies for incurable diseases as, if anything, a stronger justification than for infertility, which can cause profound suffering but is not actually fatal.

The argument is that it is justified by the intention of the possibility of treating extremely serious diseases in another human being. But is this sufficient cause to justify the application? Ethically we recoil at the idea of killing a human being in order to provide spare parts for another, so should we allow an early embryo to be destroyed to provide cells for potential transplantation?

Others argue that not all possible uses of embryos should necessarily be permitted. We should look at each particular use. Most embryo research has been on issues of infertility, where the embryo is still considered as an entity. To the extent that embryo research may be allowed for such limited purposes a measure of instrumentality towards the embryo has been accepted. The question is whether this constitutes an allowance for all instrumental uses, or only some?

They maintain that the use of embryos for cell replacement marks a different and more instrumental use of embryos. The argument is that cell replacement therapy would mean that the embryo would be used as a source of selected cells, instead allowing its normal development to become the totality of all the cells that make up a human being. In effect, this would turn an embryo from being seen as an entity in itself to being treated merely as a resource, a means towards an end. This would push it beyond the acceptability bounds of embryo research.

Against this argument, some say that an early embryo is potentially all the cells of the human body, and one is not destroying it, but merely using it to become certain cells and not others. By the same token, however, the embryo is prevented from developing in its normal complete fashion. (It is not just "taking a cutting" from the embryo, because the whole embryo would be discarded.)

The 1984 Warnock Report implied that the embryo should be accorded "a special status", although the notion was left somewhat ill defined. This new proposal would seem to remove any vestiges of special status, and push the present ethical compromise firmly down the "just a balls of cells" side and much further away from its connection with a delivered baby. The proposed research would seem to reduce the embryo from being an entity in itself to having only the status of a resource from which convenient parts are taken.

In contrast, the Farm Animal Welfare Council report on animal cloning, which came out a week after the HGAC/HFEA report, made a careful review of the ethics of cloning animals and says we should not see animals merely as a means to an end. For some it seems strange indeed that, at a time when animal experimentation is increasingly being brought into question, the use of human embryos seems to be much more acceptable.

What about using Spare IVF Embryos?

A further complication is that the main source of embryos would not be created for the purpose of producing stem cells, but would be spares from IVF treatments. It is estimated that there are tens of thousands of unwanted embryos, whose likely fate is simply to be flushed away. If they are going to be destroyed anyway, why not then use some of these for a good purpose in providing replacement cells for diseases like Parkinson's, heart failure and diabetes.

This argument evidently convinced many MPs and Lords who both voted by a 2/3 majority to extend the present Act to allow for embryo research for serious diseases. The Church of Scotland General Assembly in May 2001 disagreed and said that if the intention was to create an IVF embryo for procreation, than we should not use it for a different purpose simply for its cells.

Should we create Cloned Embryos for Cell Replacement Therapy?

As explained above, if the source of replacement cells came from a spare IVF embryo there is the risk of cell rejection by the body. This gives an impetus for creating a cloned human embryo, say from one of the patient's skin cells, and then using this to generate stem cells and thus the requisite replacement cells. Although this was not the subject of a separate vote, this possibility was automatically accepted by Parliament, provided no reproductive use was made of the embryo. It raises a number of ethical problems, however.

If we have decided it is unethical to create a cloned baby, then how can it be ethical to create a cloned embryo, knowing full well it would have to be destroyed on ethical grounds, because it was unethical to allow it to go to term to produce a cloned baby?

Is allowing research which allows the creation of cloned embryos a "slippery slope" to developing cloned people? Once cloned human embryos were created, there would be strong pressures to go to the next step and allow them to be implanted, whether legally or not. Some researchers, perhaps with financial inducements, could be tempted to find someone willing to be a surrogate mother and bring a spare cloned embryo to term.

This does not represent an absolute reason to oppose such research, since it presumes an outcome which could be prevented anyway. At best it would be a precautionary measure indicating a place to stop. There would be no guarantee that an irresponsible scientist would not attempt it outside the law, whether or not research into therapeutic uses was permitted.

The Church of Scotland General Assembly reluctantly agreed to using cloned human embryos provided there was no other alternative, but on different grounds from MPs. It argued that if the intention was never to create a cloned baby, the cloned embryo was never intended for human procreation and could therefore be used as a source of stem cells.

Can we do without using Human Embryos?

One solution would be to obtain stem cells which are produced by some tissues in the adult body. These could be obtained via the patient's own body. This would be easier and avoid many ethical problems, as well as the risk of cell rejection. Unfortunately no one knows if adult stem cells could be reprogrammed as easily, in sufficient numbers and as effectively as embryonic stem cells.

Some recent preliminary research findings have shown indications of wider reprogramming than had been expected, but these are very early days and it is much too soon to build hopes upon.

The Roman Catholic Church has urged that instead of using embryos, research should be concentrated on adult stem cells and on related sources of stem cells from placental cord blood. While many researchers would wish these adult sources were indeed able to provide the full range of cell types as embryonic stem cells, current scientific understanding would still see this as quite a remote hope.

They would not wish to put all their eggs in this basket, for fear that a situation arose of being able to treat some diseases but not others, if it turned out that adult cells were not able to make the same range of cell types. Leading scientists in this field in the UK are therefore urging that both routes are researched for the time being, to find out which works best in which situation.

A pragmatic hurdle to using cloned embryos has been posed that there is no serious prospect that enough human eggs would ever be available to treat the number of potential patients who might benefit from a successful outcome to such research.

One suggested solution is to create hybrid embryos by fusing human cells with a denucleated cow egg, of which there is an unlimited supply. Stem cells from the hybrid embryo could be reprogrammed to produce normal human cells.

The Church of Scotland and the Donaldson committee both opposed this. While it could never create a viable embryo, it would avoid one ethical problem - the creation of a human embryo which could otherwise go to term - but create another over such a fundamental mixing of human and animal entities. There are also major safety questions.

A less contentious but scientifically ambitious aim is to find a method that enabled replacement cells to be generated without going through an embryo at all. This would entail taking an ordinary adult body cell and reprogramming it directly to the desired type of cell without going through an intermediate totipotent embryonic state.

It would be an appealing concept, if one could take a skin or blood sample and reprogramme the cells directly to become, say, nerve cells. As with using adult stem cells, few would find that ethically objectionable. It would require some remarkable scientific breakthroughs, but a first step has been reported of reprogramming a cow skin cell into heart muscle cells. Much of the research would be on animals, but there would come the point when no further progress would be possible without some research using cloned embryos as an intermediate stage.

This poses a serious ethical dilemma. Would it be ethical to allow limited research where cloned embryos were created, with the sole purpose of developing a method that enabled replacement cells to be generated in future, without going through an embryo? Could a distinction be made between a limited research use? Might we allow such research with a proviso that if a point was reached where it was clearly most unlikely to be able to generate cells without creating cloned embryos, then the research should then stop?

Other ethical dilemmas

To justify a course of action with profound ethical difficulties, however, one must be honest about its chances of success. The science of both mammalian nuclear transfer cloning and human stem cells are in their very early stages. No one can be sure at this early stage whether nuclear transfer cell replacement will actually produce therapies. There is a formidable list of experimental hurdles to overcome. How far is research justified? Gene therapy promised much but has ended up raising premature hopes for patients, since it is a long way from delivering real treatments.

There are safety issues. No one knows how successful cloned cells would be on patients, nor what risk there is of cultured cells becoming cancerous.

Commercialisation and Ethics

Two UK patents have been granted on cloning technology to the Roslin Institute, and licensed Geron Corporation and PPL Therapeutics. Two important issues arise from this. The first concerns the patent, the second the ethics of some of the technologies it would be used for.

The Church of Scotland has expressed its objection to the patenting of genes or transgenic animals and plants, on the basis that they are God's creation, a discovery not an invention, and something which no one should claim exclusive rights about. These patents are different, however, because they are about the cloning technology, which is indeed inventive, and passes the normal grounds for a patent. The ethical issue is what it would be used for.

There is great concern about the impact of a monopoly on an invention upon the development of potential therapies. When a new technology begins, the first patent is usually very broad in what applications it covers.

But broad patents are often criticised because in the past they have sometimes hindered development because one organisation held too much control. When it applies to potential medical therapies, this can also give too much power to charge high costs to use the invention. Society has given Geron and their collaborators certain rights. In return, we must now require Geron to exercise a clear social responsibility on how they use those rights.

They must ensure that the benefits of their research are available not just to a few rich patients, but to all. This means putting human needs before profits. They must ensure that their position will only be for ethical purposes.

In the current climate of scepticism over biotechnology in Europe, it is important that decisions over technologies such as these are made with as full a public consultation as possible.

These are not matters for the experts alone. Indeed governments can make major changes to the law by small steps made by experts far away from public scrutiny. In conversations with the public, this "gradualism" emerges repeatedly as something of deep concern and scepticism. We welcome very much the new climate of openness in the UK that is emerging with regard to some areas of biotechnology, but are anxious that on this particular issue - of all issues - the pressure from the scientific and medical communities is not balanced by a consideration of the wider ethical issues.

Further information visit http://www.srtp.org.uk