Let stem cell research begin

• New developments in stem cell and gene therapy technology could provide a permanent cure for patients with genetic and degenerative diseases
• Limited stem cell research has now been given the go-ahead in the UK, but the UK government has still failed to put a positive case for such research
• Even the proposals put forward by bodies supporting genetic research contain new constraints of their own

The UK House of Lords voted on 22 January 2001 for the proposed amendment to the 1990 HFE Act, which will allow limited stem cell research. But while this may have been a positive move, the case for stem cell research has still not been clearly made.

The UK government apparently nearly faced a crisis over renewed opposition to the regulations passed in parliament on 19 December 2000, which permitted limited early embryo stem cell research. Lord Alton and Baroness Blatch tried, but failed, to convince the Lords to oppose the regulations, on the pretence that the Lords should wait for the conclusions reached by a select committee, or for the outcome of the High Court appeal against this legislation.

An alliance of religious leaders, described by one UK national newspaper as ‘unprecedented’, has vigorously lobbied both the Lords and UK prime minister Tony Blair. But for all the talk, on both sides of the argument, about debate being delayed, rushed or needing to be wider, the hallmark of this debate is the lack of conviction displayed by the UK government.

The government has nobody to blame but itself for any renewed opposition, now or in the future, because it never won the argument in favour of allowing stem cell research in the first place. It has fought shy of putting forward a positive argument, instead preferring to emphasise that nothing has changed – or, alternately, imposing new regulations upon regulations. As a condition for voting for the amendment, the House of Lords has demanded that a special select committee revisit the issue during a nine-month period.

Amid the narrowly emotive arguments used (the ‘slaughtering of innocents’ pitched against ‘needless death and suffering’), the novel character of this research, and its real potential, has been overlooked. While some scientists, and even politicians, made a good case for stem cell research in the end, none of this changes the fact that an opportunity to understand and celebrate such scientific advance has for now been avoided.

And looking back at the debate over stem cell research shows that two years of potentially life-saving research has been squandered.

‘My own view, and that of the committee, is that stem cell research opens up a new medical frontier’, stated chief medical officer Liam Donaldson, at the launch of his report on stem cell research in August 2000 (1). In recent years, the convergence of research techniques in embryology and genetics offers the hope of fundamental new medical treatment and a more profound understanding of cell development, including processes such as ageing and the onset of cancer. The government’s acceptance of all the recommendations outlined in the Donaldson report, and its decision to hold a parliamentary free vote on extending the 1990 Human Fertilisation and Embryology Act (HFE) to cover two new purposes in embryo research, was widely welcomed as a step in the right direction (2).

When he called for an extension to the HFE in August, Professor Patrick Bateson, vice-president and biological secretary of the Royal Society, said: ‘We believe the potential medical benefits of permitting research on human embryonic stem cells are so great that an extension of the 1990 Act is entirely justified.’ (3) So why, amid all this enthusiasm, was the law not changed until 19 December 2000? Why did the government keep dithering?

Two dramatic scientific developments have driven calls to change the law, increasing the possibilities of further embryo research. The first is the discovery, with Dolly the cloned sheep in 1997, that adult somatic (body cell) nuclei could in some sense be ‘reprogrammed’, by placing them in an egg cell from which the original nucleus had been removed. An embryo can be developed from scratch, without the normal fertilisation process, using a nucleus derived from an adult cell that had already specialised (in this case, a sheep udder cell). This discovery was rapidly confirmed, with the announcement that mice, cows, pigs, monkeys and probably even humans could also be successfully cloned in this way.

The second development has arisen from 15 years of stem cell research – the study of unspecialised, undifferentiated cells that retain the ability to transform into any other cell and to replicate themselves indefinitely. By 1998 researchers in the USA had confirmed the possibility of deriving stem cells from early embryos. Stem cells can be found in humans at all stages of development, from the earliest embryo onwards. But as we develop, they become more and more specialised, capable of developing into an increasingly limited number of cell types. Early embryo stem (ES) cells, on the other hand, are ‘pluripotent’: capable of developing into all the different cell types, making them particularly useful for research purposes.

Much of the appreciation of the benefits of stem cell research has come from the discovery that, through the use of cloned stem cells, dramatic new treatments can be developed for previously incurable diseases and damaged tissue. By replacing the nucleus of an egg cell with the somatic nucleus of a patient, immunocompatible tissue could be developed to treat patients with degenerative diseases of the heart, liver, kidneys and cerebral tissue, such as multiple sclerosis, Parkinson’s and Alzheimer’s disease, and other diseases such as diabetes and leukemia. Damaged tissues, due to strokes, cirrhosis, burns and so on, could potentially be replaced.

Promising early research supports these hopes. Over the past four years, pioneering work has shown that implantation of human fetal cells into patients suffering from Parkinson’s disease provides substantial improvement. Heart muscle cells derived from mouse embryonic stem cells have been injected into – and successfully integrated with – the heart muscle of adult mice. Research using rats suggests that even spinal injury might successfully be treated using stem cells. In the future, it might be possible for cloned stem cells to be used to grow complete donor-compatible organs. Stem cell and gene therapy technology might be combined in treatment to provide a permanent cure for patients with genetic disease. If some of these research areas can be successfully addressed, then we are indeed crossing ‘a new medical frontier’.

These developments in cloning and the ability to isolate stem cells compelled the Human Fertilisation and Embryology Authority (HFEA) to recommend that the law be updated. Under the HFE act of 1990, embryo research is prohibited unless scientists can convince the authority that the research falls within the remit of one of five specified areas: the research into and treatment for infertility, congenital disease, miscarriage, more effective contraception, and development of methods for detecting genetic or chromosomal abnormalities in embryos before implantation. As far back as 1998, the HFEA’s report on cloning recommended that in addition to these five areas, the use of embryos be extended to allow research investigating treatment for mitochondrial diseases and the replacement of diseased or damaged tissue or organs (4). Both of these purposes would allow more extensive research into ‘cell nuclear transfer’ (loosely known as ‘cloning’). The extension of embryo research would also allow work on embryos to derive embryonic stem (ES) cells.

These are modest proposals. As the report noted, the HFEA already has sufficient legal powers under the HFE Act to ban reproductive cloning outright – and it even suggested that, in order to allay any remaining fears, an explicit statutory ban by parliament might be politically expedient. To reflect the new scientific developments discussed above, the authority also recommended a distinction be made between ‘reproductive’ and ‘therapeutic’ cloning. Yet two years later, and government had still failed to implement any changes to the law.

Supporters of therapeutic cloning were dismayed in 1998, when the government refused to act upon the HFEA report and instead commissioned yet another report. At the time Lord Winston described the government’s inaction as ‘immoral’ and ‘pathetic’, while the shadow health secretary pointed out: ‘We elect governments to govern us, not scientists, and it is therefore the job of government to have the courage to take difficult decisions.’ The subsequent report, entitled ‘Stem cell research: medical progress with responsibility’ (5), was received in May 2000 and has been sat upon by the government until August 2000. After all this time, the report said nothing that previous reports have not already said (6). Instead, two years of potentially life-saving research has been squandered.

The government’s acceptance of the recommendations outlined in the Donaldson report on stem cell research has been greeted as a cautious, if not resounding, endorsement of further embryo research. Yet a more critical reading of this report is required than lobbyists and supporters of further embryo research are prepared to admit publicly. Is ‘Medical progress with responsibility’ a step forward for research – or not? The two recommendations permitting limited extension to embryo research, along with the Royal Society’s original suggestion of establishing collections of stem cells for research use, are welcome. But the remaining recommendations suggest further restrictions, more bans and upholding notions that can only continue to stigmatise embryo research.

Recommendation 2 of the Donaldson report states that the HFEA should first satisfy itself that there are ‘no other means of meeting the objectives of the research’ before licensing any work using cloned embryos. Recommendation 5 calls for the progress of research involving stem cells which have been derived from embryonic sources to be ‘monitored by an appropriate body to establish whether the research is delivering the anticipated benefits and to identify any concerns which may arise’. These are proposed in a context in which embryo research is already subject to the HFE Act – whereby any embryo research that is not agreed to and licensed by the HFEA, on a case-by-case basis, is already defined as a criminal offence.

The Donaldson report makes many references to the desire for an alternative to using embryos created for the purposes of research, suggesting for example that the use of ‘reprogrammed’ adult nuclei might in the future make the use of embryos redundant. The most explicit reference is in Annex B, in which one of the questions presented to clinics and research centres as part of the consultation exercise was: ‘Are there alternatives to research on human embryos, created in vitro, to achieve the same ends? If so, is it likely that they will be available within the next five years?’ The succinct answer given by the Institute of Biology and Society for the Study of Fertility to this question is ‘no’. As they point out: ‘if we had the knowledge to know whether [animal] embryos could answer our questions about human development, we would already know enough to start working with human embryos, which would in turn make working with animal alternatives a step backwards from the goal of human therapeutic use.’ (7)

In parliament at the end of October, Conservative opposition to the 10-minute rule bill on the Donaldson report also suggested that the use of adult stem cells might already represent an alternative to the use of ES cells. But while it is true that neuronal cells have been created from adult bone marrow stem cells, this is not evidence that adult stem cells provide a comprehensive alternative for research. As already mentioned, only ES cells are pluripotent, being able to differentiate into all 216 types of somatic cell, making the study of them central to understanding the character of stem cells. They are also likely to provide the treatment option of choice in many circumstances and are easier to culture in laboratory conditions than adult stem cells.

The proposal to monitor, using an ‘appropriate body’, any research that uses stem cells derived from embryos, can only reinforce the idea that such research is morally dubious and somehow dangerous. Important research will be stigmatised and scientists will be forced to prematurely justify their research results in terms of tangible benefits. As part of the monitoring process they will have to complete paperwork unrelated to the scientific content of their work. The net result of monitoring can only mean further bureaucracy, inhibition of basic research and increasing demoralisation for the scientists.

If the further restrictions recommended are not enough, the Donaldson report proposes two bans. The first is a restatement of the criminal character of human reproductive cloning (Recommendation 7) to head off opposition claims that therapeutic cloning is ‘the slippery slope to reproductive cloning’. Citing CS Lewis in his opposition to the Donaldson report, Conservative MP Edward Leigh summed up this view: ‘The softest road to hell is the gradual one, the gentle slope, soft underfoot, without sudden turnings, without signposts.’ (8) There is currently a consensus that reproductive cloning should not be attempted at present for reasons of safety. But as many have pointed out, this is no reason to impose an all-time ban (9). As geneticist and writer Steve Jones argues ‘Many find the idea of human cloning shocking. I do not. The objections turn on genetic essentialism, the idea that a clone would be stigmatised, treated as a second-class citizen, with fewer freedoms than an organism produced by sex – in other words that rights reside in genes rather than people.’ (10)

Only if you believe people are little more than products of their DNA are you likely to fear reproductive cloning. Even after safety issues have been resolved, it is in any case likely that the demand for such technology will be very small. (Although arguably, and in contrast to the view put forward by the Donaldson report and the HFEA, it is possible to envisage legitimate reasons as to why some people might choose to have a child this way, such as rare types of infertility.)

The second ban states that ‘mixing of human adult (somatic) cells with the live eggs of any animal species should not be permitted’ (Recommendation 6). This is in response to claims made by a US company in 1998 that it had reprogrammed an adult human nucleus back to its embryonic state by fusing the cell with a cow egg (11). The truth of this claim is difficult to judge, since the results were not published. The company responsible for the research, ACT (Advanced Cell Technology), claims that such adult somatic nuclei could be used to derive human stem cells for basic medical research. Either way, to ban any basic research that might facilitate our understanding of cell development is likely to delay discovery and panders to base Frankenstein fears. Recommendation 6 confirms that scientific research is expendable in the face of ideological objections.

The recommendations display a hyper-sensitivity to the creation of embryos for use in research; particularly those created by cloning or created for the purposes of harvesting stem cells. All the recommendations reflect an underlying notion of a moral status for an embryo established by the Warnock Committee Report back in 1984 (12). By way of its potential, the committee argued, an embryo is granted special status, but not endowed with human rights. This forms the basis for all the horse-trading over the subsequent years for the ‘interests’ of embryos weighed up against the tangible benefits of research to humanity-in-being.

As the Donaldson report states, the sensitivity towards the creation of research embryos is such that ‘even some people in the middle ground of ethical opinion may not accept that balancing the benefits of the research against the stage of development of the embryo is an appropriate basis for deciding whether to allow this form of research’ (13). In other words, cloning is so repugnant that, even for those ‘in the middle ground’, the first impulse is to call for a ban. It should be remembered that it was a distinguished HFEA spokeswoman in the early 1990s, not an absolutist churchman, who first provided the enlightened insight: ‘My reaction to the idea of using fetal tissue is “yuk!”.’

Why is the government so timid about embryo research given the potential rewards? What are the risks involved? Beyond raising the possibility that the research and resulting treatments might fail and that there are many technical hurdles to be overcome, the answer currently appears to be: very few. This is hardly surprising since the required research has barely begun: halted instead by the government’s palpable failure of nerve in the face of opposition. In turn, some of the concerns raised sometimes appear to be confined to the imagination of committee members. For example, as part of the HFEA/HGAC 1998 consultation exercise (Human Fertilisation and Embryology Authority and Human Genetics Advisory Committee), respondents were asked: ‘To what extent can a person be said to have a right to an individual genetic identity?’ The question was given short shrift by respondents, with some 50 percent replying the concern was misplaced: the experience of natural identical twins demonstrates that genetic identity is not essential for a human being to be uniquely individual (14).

In the Donaldson report, ethical concerns are raised that oocyte nucleus transfer (a potential means for screening out mitochrondrial diseases in subsequent generations) might be tantamount to a modest modification of the human genome. Given the tiny numbers afflicted by these rare diseases, this is surely nonsense. Indeed, no sooner had the commission raised such fears that it conceded the numbers involved make this concern unfounded. But surely, if and when it does become possible to eradicate some genetic disease through germ line modification, this is not something to shy away from but something to be welcomed. The biggest show of timidity in the report, however, is its stated desire to anticipate ‘unforeseen concerns’ (15). The only way to procure this, as Donaldson suggests, is through the continual monitoring and assessment of incomplete research results, with its attendant downside for research progress.

Ultimately, the only way to put the case for embryo research consistently is to question the moral status with which the Warnock Committee endowed the embryo. If embryos are viewed as having a special status that marks off human embryo cells from other types of body tissue, then draconian restrictions on embryo research will continue to be inevitable. ‘Embryo rights’, coupled with the modern nervous affliction of anticipating ‘unforeseen consequences’, will mean that fundamental new medical treatment is postponed or even prevented. Alternatively, if it is accepted that a human embryo has no more moral status than any other cells in the human body – despite its potential to become a human being – then the ‘yuk factor’ would be more readily exposed for what it is: a gut prejudice against scientific advance.

Read on:

Stem cell research: the battle against Parkinson’s, an interview with Robin Lovell-Badge, by Timandra Harkness

Toby Andrew is a genetic statistician.

(1) The report of the chief medical officer’s Expert Group on Therapeutic Cloning, ‘Stem cells: medical progress with responsibility’ (‘The Donaldson report’), was published on 16 August 2000. Available here

(2) The Human Fertilisation and Embryology Act (1990). A summary can be found here

(3) Press release by the Royal Society, 16 August 2000. See the Royal Society website

(4) Cloning Issues in Reproduction, Science and Medicine, Human Genetics Advisory Commission and Human Fertilisation and Embryology Authority, published by the Department of Trade and Industry, 1998

(5) See the Donaldson report

(6) See, for example, earlier reports by the Nuffield Council on Bioethics, the Royal Society and in particular, the HFEA/ HGAC 1998

(7) IOB response to the Donaldson report, ‘Therapeutic cloning in humans: a consultation response to the Department of Health’s Expert Advisory Group on Therapeutic Cloning in Humans’, is available here

(8) Conservative MP Edward Leigh’s comments can be found here

(9) See, for example, Prometheus, issue 2, with an exchange between Ian Wilmut and Lee Silver on reproductive cloning

(10) ‘Common sense about cloning’, Steve Jones, International Herald Tribune, 16 March 1998

(11) See Associated Press article, 12 November 1998, by Alison Fitzgerald here

(12) The Warnock Report on Human Fertility and Embryology, 1984

(13) paragraph 28

(14) Appendix C in the 1998 HFEA/HGAC report ‘Cloning Issues in Reproduction, Science and Medicine’. The report can be found here

(15) p10 and p42