sBMJ | Human cloning: ethical considerations

Human cloning: ethical considerations

The debate surrounding therapeutic cloning has intensified since the granting of the first UK license for its study in August this year. Jez Fabes and Francesca Mazzola outline some of the main ethical questions

The 5 day old human embryo (blastocyst) is about 100 cells—roughly 30 inner cell mass (ICM) cells embedded in an outer layer. Removing these and culturing them leads to the production of pluripotent embryonic stem cells (ESCs) that can form any adult cell type. Current research involves removing ICM cells from blastocysts grown from the leftover fertilised eggs of in vitro fertilisation (IVF) treatment and their subsequent in vitro culture, with the donors' permission. Studying the development of ESCs into various adult tissues sheds light on early human development and may lead to novel therapeutic techniques.w1 Using ESCs from IVF, embryos diagnosed with a disease before implantation, such as Down's syndrome, permits the study of the progression of these diseases in culture and assessment of potential therapeutics.

Potential new treatments from therapeutic cloning
Tissue or cell type	Potential treatment
Skin	Burns, skin grafts
Pancreatic &bgr; cells	(Juvenile) diabetes
Neural	Degenerative brain diseases (Parkinson's disease)
Hepatic	Cirrhosis
Skeletal muscle	Muscular dystrophy

Most countries permit generating ESCs for research, except the United States, which bans governmental grants for this research, other than for 72 established lines. Unfortunately, many of these are useless for research. The US government will soon have to redress the legislation or see mass migration of researchers.

Most of the current controversy comes from the ability to dictate the genetic identity of ESCs and producing them specifically for human cloning. Cloning involves the transfer of an adult somatic cell nucleus into a donor oocyte that has been stripped of its genome. After this enucleation, cleavage starts, and six days later the resulting blastocyst has the genotype of the adult somatic cell while showing a totally embryonic phenotype. Removal and culture of the ICM cells results in ESCs genetically typed to any adult human. This therapeutic cloning is the basis of a newly approved UK research proposal.

A serious concern is the potential for reproductive cloning—implanting cloned blastocysts into the womb, with the resulting human a clone of the original adult donor. Currently, in the United Kingdom, reproductive cloning is banned, and therapeutic cloning needs government approval. The number of embryos required for reproductive cloning would be huge. The rate of mutation in the resulting mammals is high—to create Dolly the sheep, 277 embryos had to be created before a successful pregnancy. Outlawing attempts at reproductive cloning is an obvious ethical line to draw, and this is the stance taken by most governments and the US president's Council on Bioethics.w2 The obvious and undeniable association between therapeutic and reproductive cloning and the fact that research into the former will obviously facilitate attempts at the latter fuels the debate on support for therapeutic research.

Despite the obvious potential benefits of therapeutic cloning, it involves the production of many human embryos, which, after implantation, might come to term. For many people, the greatest concern is the destruction of a living human being. Also, this "life" has been created merely for scientific research. This is the central moral and ethical question to consider.

Assigning an age at which an embryo is assigned the legal, moral, and psychological status of a human being is a longstanding debate. At one extreme, techniques may be completely unacceptable to people who believe that life starts with conception; others believe that a cluster of cells does not have the same status as a human adult. The moral question of the "worth" of an embryo is that raised by opponents of abortion, and this argument is unlikely to be resolved soon. Some rationalisation is necessary if therapeutic cloning is to get the same public support as IVF, otherwise this technique may get the same research stunting vilification that vivisection has.

One important distinction between the abortion and cloning debates is that the blastocyst from therapeutic cloning is merely an activated egg, containing the genetic material of one other person. It is not the product of a human coupling or a real fertilisation. The minimal quality of life likely to be realised by any of these cloned embryos and the artificial creation of life are more relevant issues. Designating an age for human status is irrelevant; but is it acceptable to produce and destroy primitive human life for the sole benefit of the general population?

YORGAS NIGAS/SPL
Blastocyst

Potential benefits must be taken into account. The ability to produce an ESC line genetically matched to an individual, with cell transplantation, could permit the production of new organs or regenerative implants for diseases (table).w3 The absence of tissue rejection would free recipients from a lifetime of immunosupression and complications. Furthermore, ESCs derived from patients diagnosed with diseases that cannot be picked up pre-implantation in IVF and hence cannot be represented as an ESC line derived in this manner, would be of critical importance in physiological drug testing.

If most of the public can accept the purposeful creation and destruction of fertilised eggs to facilitate pregnancy, supporting the creation of blastocysts that could improve the quality of life of thousands of people is reasonable. Eventually, alternatives to therapeutic cloning may be discovered, most excitingly the possibility of "reverse programming" an adult somatic cell into an embryonic precursor. Without funding research into the differentiation of ESCs, however, these advances are likely to be delayed or impossible. A strong government stance and backing for publicly funded and accountable research will promote advances.

Jez Fabes, PhD student, International Spinal Research Trust, University College London
Email: j.fabes@ucl.ac.uk

Francesca Mazzola, second year medical student, University College London

studentBMJ 2004;12:393-436 November ISSN 0966-6494

See "Beginner's guide to genetics" in Education, p 399.

Responses published this month

Articles	Responses
EDITORIALS Human cloning: ethical considerations Jez Fabes, Francesca Mazzola (November 2004)	Kaushal Raj Pandey (November 1, 2004) Read this response

EDITORIALS Human cloning: ethical considerations Jez Fabes, Francesca Mazzola (November 2004)	Helen Barratt (November 10, 2004) Read this response

	EDITORIALS Human cloning: ethical considerations Jez Fabes, Francesca Mazzola (November 2004)
	Kaushal Raj Pandey (November 1, 2004) fourth year medical student, IOM, TUTH krpandey702@emailaccount.com
	The editorial addressing the controversial issue of human cloning ¹ was a nice surprise breaking the silence on the part of the journal. The debate has got intensified globally because of UK licensure on it and also the US presidential election. The US president’s policy does not allow the federal money in the research creating human embryos and stem cell lines after August 9, 2001. The same decision allows the grant for research in stem cell lines created before that day. This allows basic study but they have little or no clinical importance as all those cells were cultured in contact with mouse cells and bovine serum, the transplantation of the product of which faces the same immune barrier as organ transplantation ². And even if these studies (with pre-2001 stem cell lines) are tremendously successful to generate organs from the stem cells, what’s its clinical application if you don’t allow making cloned embryo for therapeutic purpose now. In the USA, laws at the federal level are generally silent about embryo, stem cell, and cloning research. When federal funding is provided, however regulations apply that severely restrict such work ³. If that allows privately funded researcher to create cloned embryo and stem cell lines for research there is no point blocking federal money showing the concern for misuse of therapeutic clone to reproductive form because if the former can be regulated later too can be. The comparison of therapeutic cloning and discarding of embryos with abortion does not look meaningful to me as one is totally in vitro procedure and later all in vivo development and hence undoubtedly living human being. If you talk in terms of potential, even in IVF for assisted reproduction more than one embryo is created and the unused one is stored or discarded. But if that is acceptable then why not with those created for stem cell. US backing Costa Riccan proposal, recommended a complete ban on both reproductive and therapeutic cloning in an international convention on human cloning recently. The attempt to ban therapeutic cloning globally does not seem a wise decision to me. This tarnishes long held image of US as the leader in the science (even in moral respect). The Belgian Proposal with UK backing to ban reproductive cloning but allow UN member countries to make their own decisions on therapeutic cloning ⁴ I believed was a balanced one for both the science and patients. References: Fabes Jez, Mazzola Francesca. Human cloning: ethical considerations. studentBMJ 2004;12;393-436(November. 2004) Daley George Q. Missed opportunities in embryonic stem cell research. N Engl J Med 2004 351:627-628 Tauer Carol A. International Policy failures: cloning and stem-cell research. Lancet 2004; 364: 209-14 Mayor Susan. United Nations fails to agree on human cloning BMJ 2004;329:996 (30 October),

	EDITORIALS Human cloning: ethical considerations Jez Fabes, Francesca Mazzola (November 2004)
	Helen Barratt (November 10, 2004) Final year medical student, Imperial College, London helen.barratt@imperial.ac.uk
	Editor, Jez Fabes and Francesca Mazzola provide a useful overview of the issues at stake in the therapeutic cloning debate, but I wonder if the points they raise need setting in a broader context? Cloning for biomedical research has been the subject of much recent political discussion, fuelled by the American election earlier this month, as well as the work of high profile spokesmen such as Ron Reagan Jr. and the late Christopher Reeve, both of whom have done much to raise the profile of - as well as the public’s hope in – the power of embryonic stem cells (ESC) to enable the blind to see and the lame to walk. US presidential candidate John Kerry went so far as to suggest that cures for all manner of diseases ‘could be right at our fingertips’, were it not for ‘the stem cell ban’ imposed by George Bush¹. Whether the Bush administration has truly banned all ESC research is open to debate, but it is clearly wrong to suggest that treatments are ‘at our fingertips’. As Fabes and Mazzola point out, work in this area is likely to prove difficult and complex to carry out. So far success in the field has been limited, and research using ESCs has highlighted several potential dangers to the technique, including tumour development. The public are holding out for cures for Alzheimers’ disease, diabetes, spinal cord injury etc etc, as promised by politicians and the media, yet these are probably decades away. Fabes and Mazzola refer to ‘the possibility of “reverse programming” an adult somatic cell into an embryonic precursor,’ yet research involving so-called adult stem cells (ASC) has proved extremely promising, demonstrating that these cells, present in all of us, have much more flexibility to replace damaged cells than was previously thought. For example, work in mice has shown that blood stem cells could generate nerve cells², as well as repairing damaged muscle³. In reality, much more extensive research is needed in this area as well before there is any real promise of cures, but why is it that we seldom hear about this work? The media on both sides of the Atlantic appears to have been dazzled by the promise of ESCs, to the extent that reality has become a little hazy, and objective ethical discourse seems to be considered irrelevant, if not plain obstructive. It’s wrong of advocates to suggest that ESC therapies ‘could be at our fingertips’, and cruel to play on the public’s fears and sympathies to further a political cause. The medical profession and the scientific press need to careful examine the (real) wider evidence, and consider their responsibility to redress the balance. Helen Barratt References: Kass L. Playing politics with the sick. Washington Post 2004, 8 October: A35 Brazelton TR et al. From marrow to brain: expression of neurol phenotypes in adult mice. Science 2000; 290: 1775-9 Gussoni et al. Dystrophin expression in the mdx mouse restored by stem cell transplantation. Nature 1999; 401: 390-4.