Human Cloning - Potential for Misuse

Ó Ovulation Method Research and Reference Centre of Australia

The backgrounds to, and process of, the two papers differ. The AHEC paper had been distributed, in draft form, to a wide range of individuals and organizations seeking comment. Almost 50 responses were received from scientists, lawyers, IVF practitioners, theologians and institutions (including the AAS). The draft document was substantially rewritten in the light of these submissions. The AAS Council paper was developed by a small working group. A meeting to discuss the issues raised by human cloning was held at an early stage, but no draft of the paper was made available to it.

Both papers were prepared against a background of overseas news items on cloning. Dolly, (the sheep cloned after almost 300 attempts) had been introduced to the world in 1997. She was virtually identical with the ewe that provided a mammary gland cell used in her creation. In 1998, announcements on the successful production of human embryonic stem (ES) cell lines came from two U.S. laboratories. Although directed by established scientists holding university posts, both of the laboratories concerned were privately established entities, a procedure adopted in response to a U.S. government proscription of public funding of research using human embryos or fetuses. Both these laboratories were funded by a small biotechnology corporation, Geron, trading in the stock of which increased 40-fold with the announcement of their success. In early 1999, it was announced that Geron had added Ian Wilmut, the creator of Dolly, and his technology to its stable.

The scientific and commercial implications of these developments are substantial. Dolly was unique in being identical with an existing, mature individual (cloning had previously been achieved only with embryonic or fetal subjects). ES cells, previously only available from a few inbred strains of mice, retain the capacity to differentiate into all of the specialized cells of the body. (Consequently, it is anticipated that ES cells could be used to produce any type of body tissue.) While their potential applicability to clinical transplantation had been recognized for some time, a limitation to their use was that any recipient patient, other than an identical twin, would require immuno-suppression with its attendant disadvantages. The development of the "Dolly technology" raised the possibility of producing an embryo, and from it an ES cell line which would be genetically identical with the patient, so removing any need for immuno-suppression. Any advantages likely to accrue from applying this technology to the production of spare tissue identical with the prospective recipient may have to be qualified by a very recent report which suggests that Dolly's cells may be as old as the mammary cell from which she came.

Apart from its application to transplantation, two other human uses proposed for cloning include basic research on cell biology, an activity which could also be extensively studied, as in much biomedical research, with non-human cells, and the production of new individuals destined for birth.

The AHEC and AAS Council reports were at one in recommending that informed community discussion on potential benefits and risks of cloning technology should be encouraged and that cloning to produce human fetuses should be prohibited. A major difference arose in attitudes to legislation. AHEC recommended that the Minister urge States and Territories other than Victoria, South Australia and Western Australia (which have legislation) to introduce legislation to limit research on human embryos according to principles set out in the 1996 National Health and Medical Research Council (NHMRC) ethical guidelines on assisted reproductive technology (ART). The AAS Council requires that research should not be prevented "by unduly restrictive legislation in some States" and that existing "restrictive legislation ... be repealed".

Whereas both reports recommended oversight of research using human embryos, their approaches diverged. AHEC opted for statutory authorities in States and Territories with power to regulate human embryo research in accordance with the 1996 ART guidelines. The AAS sought assessment of proposals by institutional ethics committees (IECs) and a national panel of experts under NHMRC aegis. (Experience suggests that some IECs lack peers and can be subject to influence, whilst a national panel may be too remote to be effective.)

To declare my interest in this subject, I was a member of AHEC at the time of issue of the ART guidelines and of the cloning report both of which reflected a consensus view of that diversely constituted Committee. I believe that the AAS Council's paper invited substantial criticisms. The paper reads as if the science and the values of its authors have become heavily intertwined.

The ethical approach taken by the AAS Council is decidedly consequentialist (its members are of course entitled to adopt this approach should they choose to do so). The emphasis of the paper is upon considering the possible outcomes rather than considering the ethical status of the processes likely to be entailed in attaining those outcomes. If one adopts this approach of whether an action is right or wrong on the basis of its predicted outcomes, it becomes necessary to assess the likelihood that the predictions are accurate. The paper is uninformative in this regard. Whilst an argument can be raised that it is not possible to determine whether expectations will materialize unless testing is permitted, it is salutary to recall the point emphasized by Ian Kennedy in his Reith Lectures (1981): "There are countless examples where knowledge and truth are not pursued because the pursuit would challenge values we hold more dear than them."

Opinions, as distinct from scientific data, permeate the AAS paper. Outcomes are judged to be "desirable" or "undesirable". Legislation is "restrictive". References to currently available forms of treatment which may be replaceable by cloning technology include terms such as "crude", "macabre", and "bizarre". This makes for an entertaining read but perhaps it is a trifle emotive. I doubt that any of these adjectives would survive in an AHEC exposure draft.

One consequence of interleaving data with value-based assessments appears to be some selectivity in presentation of the science. This may have been imposed by a requirement for brevity but it is, nevertheless, unfortunate. For example, there is a repeated emphasis on the novelty of it all. In citing skin as the one human organ grown in the laboratory to provide self-compatible grafts, omission of transplantation of blood stem cells, after storage as a self-compatible graft, is surprising. Skin is perhaps an atypical example for the reason that it is necessary to have proliferation of its cells in vitro so that a large mass of tissue can be returned to patients with extensive burns. In contrast, the clinical strategy underlying the transfer of other stem cells, such as those specific for blood-forming tissues, pancreatic islets, and neurons has been to transfer a small number of cells with the expectation of their adequate proliferation in the organs of the recipient.

Description as a recent advance of the demonstration of development of human fetal nerve stem cells following transplantation to an experimental animal entails a very broad use of the word "recent". Development of human fetal neurons in experimental animals has been studied intensively for at least 15 years. On the basis of these studies, clinical transplantation of the same types of cells to the brains of human patients has been undertaken since the mid-1980s (with decidedly modest outcomes).

In passing it is worth noting the assumption implicit in predicting successful transplantation of stem cells to overcome a deficiency of these cells produced by a disease, namely that transplanted cells will not be damaged by the disease process. As noted in the AHEC report, one of the leading figures in pancreatic-islet transplantation questioned this assumption: "Our personal goal as transplanters should be obsolescence", suggesting that transplantation will not provide the ultimate solution.

Probably the most interesting use of language by the AAS Council is the expression "therapeutic cloning" (to describe the production of ES cells for transplantation). This term was, I believe, pioneered by the UK Human Embryology and Fertilization Authority (HEFA) and defined as "medical and scientific applications of cloning technology which do not result in the production of genetically identical fetuses or babies" (embryos need not apply).

It is difficult to recall a better example of the semantic tactic of simultaneously focusing on an outcome, and assigning an arbitrary positive value to it, whilst de-emphasizing the means to achieve it. The dissociation between the impressions generated by the term "therapeutic cloning" and the procedures entailed was neatly illustrated by a well-resourced study of British community attitudes undertaken in 1998 by the Wellcome Trust. Initial responses to the BEFA terminology were quite favourable. However, following provision of information on what the procedure entailed, and time for reflection, substantial reservations were expressed. These related especially to the use of cloned embryos.

Many readers of the AAS paper may sense more than a hint of condescension. The assertion is made that the NHMRC guidelines on ART have been "overtaken by unforeseen advances". For the record, a published report claiming to have produced human ES cells in Singapore was available before the guidelines were prepared and, as already indicated, the possible value of human fetal neurons in transplantation has been widely discussed.

The observation by the AAS Council that alternative (i.e. non-embryo) techniques may be preferred "from certain religious viewpoints" brings to mind a 1957 paper by Michael Polanyi FRS (successively Professor of Physical Chemistry and Social Studies at Manchester University): "In the days when an idea could be silenced when it was shown that it was contrary to religion, theology was the greatest single source of fallacies. Today when any human thought can be discredited by branding it as unscientific, the power exercised previously by theology has passed over to science; hence, science has become the greatest single source of error". It appears to be legitimate to assign contentious viewpoints to anyone apart from the AAS Council.

References to Australia's "undoubted strength in medical research" in the AAS paper might reasonably be construed as pertaining to research in cloning technology. However, as one overseas reader of the position paper brought to my attention, the list of 26 references appended to the paper appears not to include any Australians.

I find it difficult to regard the position paper as anything but an advocacy document. Proposed solutions (e.g. repeal legislation, revise guidelines) take no account of the processes leading to the legislation and guidelines. Very few items of legislation in Australian history can have been subject to the exhaustive discussion preceding the Victorian legislation relating to ART. The NHMRC guidelines on ART took account of hundreds of public submissions. Compare this with the extent of "consultation" underpinning the AAS advocacy of change.

Finally, every issue has a "sleeper" which is liable at some time to move from the background to centre stage of the debate. The ethical issue of contention underlying the position paper is that of the deliberate production of embryos genetically identical with specific patients, and their destruction to produce ES cells. The spotlight has not swept over the nature of any further relationship of ES cells to embryos. Conventional wisdom is accurately reflected in the glossary to the AAS paper: "ES cells will not give rise to an embryo if placed in the uterus".

But conventional wisdom sometimes owes more to convention than to wisdom. James Thomson, the first scientist to produce authenticated ES cell lines from human embryos noted that: "It is not known whether human ES cells could form a complete viable embryo by any method, but this possibility has raised the greatest concern about derivation of human ES cells." He observed that a clump of ES cells transferred to the uterus would not form a viable fetus.

To turn the question on its head, Janet Rossant, a notable Canadian embryologist, has reported that, provided mouse ES cells were aggregated with embryos that had been experimentally manipulated so as to preclude their full development, they were "able to support complete fetal development resulting in ES-derived newborns". The experimentally disabled embryos served only to provide placental tissues and none of their cells contributed to the newborn mice. Mouse cells appear to have little, if any, capacity to differentiate into placental cells. However, Thomson has reported that his human ES cells synthesize a hormone, chorionic gonadotrophin, which is considered to be a certain marker of cells of placental lineage.

To quote the AAS (in relation to cloning in general): "development in these areas of research are likely to generate controversial issues in bioethics". Agreed.

The following correction to the originally published version of the paper has been made.

The quotation "by duly restrictive legislation in some States" in the last sentence of the first paragraph of the section Varied Responses to Cloning Technology has been corrected to read "by unduly restrictive legislation in some States".