Monday, March 9, 2009

Commentary on Embryonic Stem Cell Research

Editor's NOTE:

While several years old the commentary which follows outlines many of the still relevant issues involved in ESCR. The references are included for those who wish to avail themselves of more information.

--Dr. J. P. Hubert

Nature Medicine 7, 397 - 399 (2001)
Embryonic Stem cell research - The case against...
Michael Antoniou

Division of Medical and Molecular Genetics GKT School of Medicine, Guy's Hospital, London, UK

Although the United Kingdom government has approved the use of human embryonic stem (ES) cell/therapeutic cloning research—a move that was endorsed by the House of Lords on 22 January this year—it may not be apparent to the outside world that the British scientific community as well as the public at large is deeply divided over this issue. In the face of a substantial vote in favor of ES cell research, this division was articulated by some of those who gave evidence at the Lords session.

Despite our government's approval of this technique, some of us within the UK involved in research to develop therapies for debilitating, degenerative diseases agree with John Wyatt (Royal Free Hospital, London) when he says, "The creation and manipulation of living human embryos for the sole purpose of generating therapeutic tissue seems incompatible with respect for vulnerable human life. The redefinition of human embryos as mere biological material, as `totipotent stem cells' in order to allay public concerns, smacks of semantic trickery rather than responsible debate." (House of Lords Hansard, 22 January 2001).

Assertions that ES cells offer the only hope of a treatment for say Parkinson disease are not the case. What is evident from studies conducted to date is that adult stem (AS) cells show as much therapeutic potential as ES cells. Indeed, as Philip Jones (University of Oxford) told the Lords, AS cells offer far greater potential for cures than embryonic stem cells.

The isolation of human ES cells1, 2 and the demonstration of AS cell `plasticity'3 both took place in 1998. ES cells can be induced to differentiate into numerous cell types in culture4. Animal transplantation studies with ES cells are presently more limited, but they have been shown to contribute to the development and regeneration of the nervous system5, 6, 7. AS cell research in animal models is more extensive showing, for example, that bone-marrow−derived AS cells contribute to not only blood cell lineages but to all neuronal cell types8, muscle3, 9 and liver10, 11; neuronal AS cells have also been shown to have a broad differentiation potential12.

The main advantages of ES cells are that they can be propagated almost indefinitely under laboratory conditions; they can be easily genetically modified and, in principle, be induced to differentiate into any desired cell type. However, the wide-scale application of ES cells by necessity involves a `therapeutic cloning' step to overcome problems of tissue rejection after engraftment. This in turn raises major practical considerations. First, a large supply of human eggs will be required as this procedure is very inefficient; and second, the treatment procedure becomes very time consuming, labor intensive and as a result expensive. Moreover, ES cells will need to be induced to differentiate down the desired cell lineage before implantation in order to avoid teratoma (tumor) formation6. This potentially limits ES cell applications in certain circumstances as it renders them incapable of self replication, requiring further rounds of treatment as the original graft progressively ages and degenerates.

AS cells, however, can be readily obtained, grown and if necessary genetically modified from, for example, the patients' own bone marrow. Therefore, problems of rejection after engraftment back to the patient do not arise, thereby negating the need for a therapeutic cloning step. Admittedly, AS cells are, at present, more difficult to propagate en masse under laboratory conditions. The more restricted differentiation potential of AS cells is also seen as a major limitation to their use. However, from a safety point of view this may be advantageous as it reduces the chances of inadvertent AS cell proliferation in a part of the body where it is not desired. Many years' experience within the medical field of bone-marrow transplantation also shows that AS cells are not prone to teratoma formation. In addition, AS cells appear to retain their self-replicating capacity while contributing to tissue development or regeneration8, 9.

It has also recently been claimed, by Ilham Abuljadayel of the Dublin-based company Tristem, that T-cells can be induced to undergo a process of `retrodifferentiation' to generate virtually endless supplies of pluripotent AS cells13. Although this work has yet to undergo the scrutiny of scientific peer review, it has been independently verified in both academic (Adrian Newland, Royal London Hospital, London) and industry (Anthony Lockett, Covance, Harrogate, UK) settings, clearly raising further exciting therapeutic possibilities14.

Regardless as to which option is pursued, the clinical use of either ES or AS cell technology is still many years in the future. As Neil Scolding (Frenchay Hospital, Bristol, UK) warned attendees at the Lords' meeting, that, "there are two fallacies, one that cures from embryonic stem cells are imminent and the other that adult stem cells are unlikely to be as effective." This is a point agreed upon by the UK Chief Medical Officer Liam Donaldson's report of 1998 on ES cell/therapeutic cloning recommendations.

Peter Andrews (University of Sheffield, UK), who hopes to develop ES cell/therapeutic cloning technology, also acknowledged this point when he wrote, "I find it difficult to envisage routine use [of ES cells] on other than selected volunteers in the next 10 years"15. Therefore, there is a risk of raising false hopes within patient groups by giving the general public the impression that ES cell/therapeutic cloning treatments are about to happen once research is given the go-ahead.

As it is widely agreed that the generation of cloned human individuals is highly undesirable, it is important to appreciate that the distinction between `therapeutic' and `reproductive' cloning is slight, as these two options differ only after a viable, cloned human embryo (blastocyst) has been generated. We may find the thought of human clones abhorrent but there are organizations (for example, and and individuals, such as Severino Antinori in Rome16, that are totally committed to this end.

Even scientists who are staunch supporters of ES cell/therapeutic cloning technology within the UK have admitted that reproductive cloning is "inevitable"17. Thus, how will the UK government ensure that ES cell/therapeutic cloning techniques developed in Britain will not be abused by being taken forward to support reproductive cloning in an unregulated part of the world? Is our government prepared to lead the way in the establishment of not only national but also international law prohibiting reproductive cloning? Once in place how will governments police the `global village' to make sure this legislation is not violated? Would it not be wise to at least wait until international law is in place banning reproductive cloning before embarking on a program of ES cell/therapeutic cloning research?

Technical and legal problems can in principle always be overcome, but the major ethical and moral objections to the use of ES cell/therapeutic cloning are much more difficult to address and clearly constitute deep human concerns that can be neither ignored nor lightly dismissed. The issues raised include not only fears that ES cell/therapeutic cloning will ultimately lead to reproductive cloning and genetically engineered human beings, but also whether embryos should be created solely for the purpose of providing `spare parts' for others, reducing human life to a purely utilitarian value.

The UK has already received condemnation from Germany when the deputy chairman of the Reichstag's ethics committee, Hubert Hueppe, said that it was cannibalistic to "breed a human being, only to kill it, disembowel it and impregnate something with it." Such strong statements serve to highlight the fundamental nature of the ethical issues that are raised.

The UK position has also gone against not only the decision of the European Parliament (Strasbourg, 7 September 2000) but also the advice of a report sponsored by the European Commission by the 12-member European Group on Ethics in Science and New Technologies which recommended "prudence" and a precautionary approach saying that, "At present the creation of embryos for somatic cell transfer would be premature"18. John Wyatt expressed the ethical dilemma well when he said, "I and many of my fellow health professionals have a profound disquiet about the introduction of therapeutic cloning."

Eleven religious leaders headed by His Grace, the Archbishop of Canterbury, the Chief Rabbi, the Cardinal Archbishop of Glasgow, the President of the Muslim College, the Director of the Sikh Network and leaders of Christian denominations within the UK took the unprecedented step of cosigning a letter to the UK parliament House of Lords encouraging members not to endorse the British government's position to allow ES cell/therapeutic cloning research but to take time to reflect on the ethical and moral consequences of this work more carefully.

Therefore, despite the Government's vote in favor of allowing ES cell/therapeutic cloning research within the UK, debate and objections are as prevalent here as in those countries that are still undecided as to which route to take. In my view, given the lack of agreement over ES cell research within the scientific community as well as general society both nationally and internationally, governments around the world should back major initiatives in AS cell research which could harbor the same if not a greater and safer therapeutic potential, and avoid the problems of working with ES cell/therapeutic cloning. Moreover, these practical and especially ethical problems associated with the ES cell/therapeutic cloning should not necessarily be viewed as a setback, as they can encourage investigation into AS cell alternatives as has already happened in the USA (ref. 19).

Note: This commentary expresses the personal opinion of the author and does not represent a position statement of either the Division of Medical and Molecular Genetics or the GKT School of Medicine.


1. Thomson, J.A. et al. Embryonic stem cell lines derived from human blastocysts. Science 282, 1145–1147 (1998). | Article | PubMed | ISI | ChemPort |
2. Reubinoff, B. et al. Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nature Biotechnol. 18, 399–404 (2000). | Article | PubMed | ISI | ChemPort |
3. Ferrari, G. et al. Muscle regeneration by bone marrow-derived myogenic progenitors. Science 279, 1528–1530 (1998). | Article | PubMed | ISI | ChemPort |
4. Lee, S.-H. et al. Efficient generation of midbrain and hindbrain neurons from mouse embryonic stem cells. Nature Biotechnol. 18, 675–679 (2000). | Article | PubMed | ISI | ChemPort |
5. Benninger, Y. et al. Differentiation and histological analysis of embryonic stem cell-derived neural transplants in mice. Brain Pathol. 10, 330–341 (2000). | PubMed | ISI | ChemPort |
6. Liu, S. et al. Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proc. Natl. Acad. Sci. USA 97, 6126–6131 (2000). | Article | PubMed | ChemPort |
7. Brüstle, O. et al. Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 285, 754–756 (1999). | Article | PubMed | ISI | ChemPort |
8. Brazelton, T.R. et al. From marrow to brain: expression of neuronal phenotypes in adult mice. Science 290, 1775–1779 (2000). | Article | PubMed | ISI | ChemPort |
9. Gussoni, E. et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 401, 390–394. | PubMed |
10. Peterson, B.E. et al. Bone marrow as a potential source of hepatic oval cells. Science 284, 1168–1170 (1999). | Article | PubMed |
11. Alison, M.R. et al. Hepatocytes from non-hepatic adult stem cells. Nature 406, 257 (2000). | Article | PubMed | ISI | ChemPort |
12. Clarke, D.L. et al. Generalized Potential of Adult Neural Stem Cells. Science 288, 1660–1663 (2000). | Article | PubMed | ISI | ChemPort |
13. Abuljadayel, IMSS and Dhook, GJ. A method for preparing an undifferentiated cell. UK Patent GB2297558 (1995).
14. Times of London, 15 January 2001.
15. The Daily Telegraph, London, 24 January 2001.
16. The Sunday Times, London, 28 January 2001.
17. The Independent, London, 30 August 2000.
18. Dickson, D. European panel rejects creation of human embryos for research. Nature 408, 277 (2000). | Article | PubMed | ISI | ChemPort |
19. European Ethics Committee. Ethics can boost science. Nature 408, 275 (2000). | Article | PubMed | ISI | ChemPort |