Select Committee on Science and Technology Written Evidence

Memorandum 13

Submission from Peter McCullagh


  The overriding reason advanced for requiring experimental production of animal/human hybrid embryos by means of the introduction of human nuclei into enucleate animal oocytes has invariably been that it will be impossible to source the numbers of oocytes likely to be needed for this type of procedure from human donors. The three uses for animal/human hybrid embryos produced in this manner that have been identified by the most comprehensive review of the subject to date involve research, training and clinical application. It is submitted, in response to these, that the outcomes of the first use can predictably be guaranteed to be quite uninterpretable, that the second use is entirely unnecessary and that the third will, on grounds of Good Manufacturing Practice, remain totally unacceptable.


  I am a member of the Australian National Health and Medical Research Council Embryo Research Licensing Committee and have honorary appointments in a veterinary faculty of one Australian university and in a medical research school at another, but this submission expresses exclusively my personal views which are not purported to be those of any organisation. I have had a career in medical research extending over four decades which has investigated cell and tissue transplantation, including xenotransplantation and production of interspecies chimaeras, and which has relied heavily upon the application of microsurgical techniques to sheep embryos and fetuses.


  I assume that the Committee has allowed itself some semantic latitude in the issue which it wishes to examine. In the first place, the experimental proposal under consideration could be more accurately defined scientifically as pertaining to human/non-human hybrids. What is under consideration is the regulation of interspecies chimeras in which one of the species of animal is the human. I shall forgo pedantry and refer hereafter to animal/human hybrids.

  A second, cognate issue is the distinction between a hybrid and a chimera. I note that the two terms fall within the purview of the Committee and my comments relate exclusively to hybrids. A hybrid is an animal (or it could be a plant) in which all of the component cells are identical with each other, all having been derived from parent organisms from two different species (although the term is used scientifically with equal frequency to describe, for example, animals derived from two genetically different strains within one species). A chimera is an animal which contains cells from two (or more) different species. That is all of its cells are not genetically identical with each other. The term owes its origin to a mythological animal composed of parts from different species. Some commentators have been so unkind as to remark on the aptness of the terminology in its present use.


  I believe that the most comprehensive recent examination of the issue of animal/human hybrids is that included in a review (referred to hereafter as the Lockhart Review) commissioned by the Australian Government (1). Having recommended that the hitherto prohibited technique of human somatic cell nuclear transfer should be authorised under licence, the Lockhart Committee expressed its concern that changing existing legislation to permit nuclear transfer and related technology would lead to an increased demand for donation of human oocytes. In its report, the Committee responded to this concern in two ways. The first was to recommend the strengthening of legislation prohibiting oocyte commerce (necessarily leaving aside the reality that jurisdiction over this could only be exercised within Australia). The second response, intended to forestall the development of a free market in human oocytes, was to recommend that permission could be given, under licence, for the production of animal/human hybrid embryos by the transfer of human nuclei to enucleated animal oocytes. Interestingly, this was the sole casualty among 53 recommendations when the Australian Parliament voted to implement the Lockhart Review in December, 2006.


  "Lockhart" nominated three ways in which animal/human hybrid embryos could potentially advance biomedical science, namely as a research resource, as a training resource for "embryo embryologists" and as a clinical resource. I submit that closer examination of these claims fails to support any of them.


  The thorough development of new therapeutic protocols in relevant animal models was a sine qua non in clinical medicine prior to the availability of large numbers of human IVF embryos which led to its omission in the further development of assisted reproductive technology. Use of non-human animal models of human diseases and the development of possible therapies for them continues to be mandatory in other fields of medical practice. That said, it is essential to distinguish between the potential scientific value of experiments undertaken in a single, well understood non-human species and observations made in, for example, a human/cow hybrid. Any experiment completed in a species such as mouse, rat or sheep has necessarily to be re-interpreted in the light of our knowledge of differences between that species and us before any conclusions drawn from it are applied, very tentatively, in clinical practice. Given the complete lack of knowledge of how the development and function of the human/cow entity will resemble that of either contributant species, the experimental data will predictably be quite uninterpretable. The potential of an experiment, in any discipline, to add to the sum of knowledge is only as good as its capacity for interpretation.


  If the Committee inquires, I believe it will find that any well established IVF facility relies heavily on the use of non-human species (usually the mouse) for training its technicians until they are considered to be sufficiently competent to commence on the simplest human clinical procedures. It has always been thus. A former research director of the Jackson Laboratory, Dr Wes Whitten, in explaining his exclusive use of the mouse observed that: mouse embryos proved to be useful models for human ART and they are still being used for teaching ART, for developing new techniques and for quality control of media, equipment and techniques (2).


  Members of the Committee who have engaged with issues of human embryo research in the past may recall that one of the most compelling arguments for the derivation of additional human embryonic stem cell lines then was to avoid potential contamination with molecules of non-human origin. The two sources of this were "feeder" layers of mouse fibroblasts on which the ES cells were maintained and fetal calf serum, a common component of culture media. It is now feasible to derive human cell lines without exposure to either of these potential contaminants.

  Concern with potential contamination of human ES cell lines by non-human molecules sprang from altruistic, legal and commercial considerations (in varying proportions, I suspect, depending on the identity of the researcher). The risk of cross-species adaptation of viruses (eg SIV > HIV) or prions (eg BSE > vCJD) is now recognised and to paraphrase a recently retired statesman "there are things we don't know that we don't know". With respect, a previous British Government's record in dealing with BSE was appalling, both in relation to its own citizens and to those in developing nations in receipt of exported stock feed that could no longer be used in the UK. The risks from any cellular product of a human/cow hybrid cell line, if this was introduced into a clinical trial, would be utterly unacceptable for any properly constituted institutional ethics committee.

  Ignoring ethical implications (if some find that to be an option), the products of a hybrid cell line would have to comply with 2007 Good Manufacturing Practice and to satisfy the US Food and Drug Administration or be a commercial dead duck.

REFERENCES  (1)  Australian Government (2005). Legislation Review: Prohibition of Human Cloning Act 2002 and the Research Involving Human Embryos Act 2002, Reports, Canberra, December 2006.

  (2)  Ali, J (2003). A practical guide to mouse preimplantation embryology and human assisted reproduction technology. Ladybrook Publishing.

January 2007

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