Select Committee on Science and Technology Written Evidence


Memorandum 59

RESPONSES TO LETTER[71] FROM THE COMMITTEE TO EXPERTS IN EMBRYO RESEARCH

Submission from Alison Murdoch, Institute of Human Genetics, Newcastle University

  I confirm that I was at the meeting on the 30 November 2006. I do not recall anyone at the meeting speaking against the creation of hybrid or chimera embryos in vitro. On the contrary, there was general agreement that work with animal cells was essential if this are of science is to develop significantly. This includes the in vitro use of combined animal and human proteins, cells or tissue.

  I do not support the government plans that you have quoted. Their proposals are not logical. If it is considered that at some time in the future the creation of hybrid embryos is justified, I presume that this will be based on scientific advice that it is an appropriate and needed development. Scientific advice is that it is appropriate and needed now so why not address the problem now?

  I would also like to bring your attention to another proposal in the White Paper. Section 2.15 relates to "artificial gametes" and proposes a ban on their use for reproductive purposes. Whilst we are not yet ready to consider them (sperm or eggs) for clinical use, I do not believe that it is far away, considering the very loose definition given of "non-naturally occurring gametes". A ban in the primary legislation would be unnecessary since there are already adequate regulatory powers relating to new clinical treatments that protect both the patient and any resulting child. A ban will simply give rise to challenge in the near future and is therefore not sensible legislation.

February 2007

Submission from Professor David H Barlow, University of Glasgow

  Thank you for seeking my opinion on the question of hybrid and chimera embryos and legislation.

  I attended the HFEA embryo research meeting in November as a Member of the HFEA Scientific and Clinical Advances Group (SCAG) and as a recent ex-Member of the HFEA. In the past I have held an HFEA embryo research licence and I was Editor-in-Chief of the journal "Human Reproduction" from 2000 to 2006.

  My comment is that I believe the balance in the statement below is correct ... "the creation of hybrid and chimera embryos in vitro, should not be allowed. However, the Government also proposes that the law will contain a power enabling regulations to set out circumstances in which the creation of hybrid and chimera embryos in vitro may in future be allowed under licence, for research purposes only".

  I believe it is important that the general public are reassured that the creation of hybrids or chimeras will be not be freely possible. The suggestion that there will be specific regulations which define the circumstances in which it will be legal, in a research context, to seek to create a hybrid embryo or chimera. There will be groups in society who will consider hybrids and chimeras to be unacceptable in any circumstances. I believe that there is scientific justification for the creation of hybrids and chimeras in experimental settings and definitely without the intention of pregnancy establishment being attempted.

  I believe that the proposed wording retains control with the HFEA or its successor body for the issuing of research licenses where the proposed experiments can be justified and I believe that this is appropriate.

February 2007

Submission from Professor Jose B. Cibelli, Michigan State University

  I agree with:

    "the creation of hybrid and chimera embryos in vitro, should not be allowed. However, the Government also proposes that the law will contain a power enabling regulations to set out circumstances in which the creation of hybrid and chimera embryos in vitro may in future be allowed under licence, for research purposes only".[72]

Supplementary submission from Professor Jose B. Cibelli

  This is in response to an inquiry by the House of Commons regarding the scientific basis for performing experiments with human/animal chimeras. For the purpose of this analysis, chimeras are defined as the combination of human embryonic stem cells (ESCs) with animal embryos and or human cells and non-human oocytes.

  Please notice that I am not an ethicist and I do not endorse nor condemn these experiments. Merely I am trying to address whether these experiments could have scientific value.

  Three approaches come to mind:

  1.  The combination of human embryonic stem cells with host animal embryo during preimplantation development only. These experiments are likely to generate very little or no useful information since the period of time this chimera will develop into a late-stage blastocyst is quite short.

  2.  The combination of human embryonic stem cells with host animal embryo during preimplantation development to be later transferred into a recipient female. Scientists might be compelled to transfer these embryos into the uterus of a surrogate mother—eg of the same species from which the host embryo was taken—in an attempt to obtain human differentiated cells that can not be generated using any other approach. This is alternative can be of great value and offer new insights regarding in vivo cell differentiation processes in human. Scientists could genetically engineer human ESCs that will only develop into a specific cell type and therefore there should be no risk for those cells to contribute to the central nervous system, if that is an issue of concern.

  3.  The third approach relates to the use of Inter-Species Somatic Cell Nuclear Transfer (SCNT). It is possible to combine an enucleated non-human oocyte with a human somatic cell and artificially trigger preimplantation development. There is one report describing the production of human embryos by SCNT using rabbit oocytes as hosts. If these experiments are independently replicated, scientists will have at their disposal a powerful tool to study human somatic cell dedifferentiation without having to rely on human oocytes. There would be no scientific justification—at least to me—to attempt transferring these embryos into a uterus. All the studies can be done in vitro.

  In summary, I believe approach £2 and £ 3 have scientific merit and deserve to be taken into consideration when drafting new legislation.

February 2007

Submission from Professor Peter Braude, Kings College London

    "the creation of hybrid and chimera embryos in vitro, should not be allowed. However, the Government also proposes that the law will contain a power enabling regulations to set out circumstances in which the creation of hybrid and chimera embryos in vitro may in future be allowed under licence, for research purposes only".

  I see great scientific merit in being able to examine the effects of nuclear cytoplasmic interaction following insertion of a somatic nucleus into an oocyte to foster not only understanding the processes of dedifferentiation and dedifferentiation during early development of the mammalian (and especially human) embryo, but also to extrapolate this to understandings of cell control in cancer evolution, and the processes needed to generate stem cells in vitro. Although I also support the limited use of human altruistic or paid donors to supply human oocytes, as a gynaecologist and specialist in reproductive medicine, I believe that it would be fairer to women if use of animal oocytes for were allowed, thus reducing the demand for human material in the preliminary stages. I feel that significant progress can also be made using suitable animal oocytes, cow being particularly useful as material can be obtained from abattoir material and would not require the use of laboratory animals. I cannot see any immediate purpose for their use therapeutically and therefore strongly support their use in research only. The degree of chimerism in these cases would be small (bovine mtDNA and RNA) but the amount that might be learned about the above processes, as well as mitochondrial interaction could be enormous.

  Accepting this, I am mystified by the wording of the supplied paragraph. It seems to me that it should say "should be allowed, but only under strict controls and regulations as set out ....." allowing this work to take place immediately if required and justified after peer review. As it stands I think it is ambiguous, unnecessarily complex, and most certainly would cause delay and likely legal challenges.

February 2007

Submission from Professor Alan Trounson, Monash Institute of Reproduction and Development

  I essentially agree and believe it is important to establish regulations that allow chimeric embryos be formed under special circumstances for research.

  The recommendation is a double proposal—ban human chimeric and hybrid embryos—but introduce regulations that permits this activity under license for research purposes.

  Like many others, I think that chimeric and hybrid embryos represent a useful model for research and this should be permitted under license. Unlicensed and unregulated experiments will be a concern to the community and a licensing process will ensure some degree of monitoring that will probably relieve this tension.

  The merits of research involving mixed cell chimeras can be obvious in determining the normality of the human cells in contributing to tissue systems. There may be no other way to assess the possible preclinical usefulness and functional normality of cells derived from embryonic stem cells for instance. This could include the need to study early lineage cell types such as germ cells which may need to be combined with embryos of animal species to observe their capacity to develop into sex cells (gametes—eggs and sperm). It would be important that any chimeric animal formed should not be bred but be subject to scientific analysis. Similarly, other cell progenitors could be studied in animal models of human diseases—this is a common experiment involving a wide spectrum of cell types and disease models that are seeking evidence for repair of the disease and eventual clinical assessment in human patients.

  These experiments normally involve agreement of animal ethics committees and there may be studies in the category that are trivial and be dealt with by these committees but the combination of cells in the early embryo that could result in significant chimerism in the gonads and central nervous system may be better covered by a licensing process.

  The production of human-animal hybrids—normally understood to be a combination of sperm and eggs of two different species, can be a vexed issue. A degree of hybridization may be recognized in nuclear transfer involving human cell nuclei inserted into animal eggs. These interspecies manipulations may also be concerning even though they are experimental and be aimed at addressing the lack of human eggs available for disease specific stem cells. The merit for having a model for disease that can be interrogated in the laboratory could be very important. It seems appropriate that this should also require a license and some degree of monitoring to ensure community comfort.

February 2007

Submission from Professor Lorraine Young, Wolfson Centre for Stem Cells, Tissue Engineering and Modelling

  I completely support the current Government proposal that:

    "the creation of hybrid and chimera embryos in vitro, should not be allowed. However, the Government also proposes that the law will contain a power enabling regulations to set out circumstances in which the creation of hybrid and chimera embryos in vitro may in future be allowed under licence, for research purposes only".

  My research over the last few years has examined how the DNA of eggs and sperm restructures after fertilisation of the egg. My laboratory has shown that (1) some of the same restructuring applies to somatic cells after SCNT and that (2) considerable species differences exist in this process, especially between the rabbit and human- two species being considered in the production of chimaeric embryos for stem cell research.

  The relevant references are below.

  Nathalie Beaujean, Jane E.Taylor, Michelle McGarry, Pasqualino Loi, Graznya Ptak, Cesare Galli, Giovanna Lazzari, Donald MacLeod, Adrian Bird, Lorraine E. Young* and Richard R. Meehan (2004). The effect of interspecific oocytes on demethylation of sperm DNA. PNAS 101:7636-40.

  Beaujean N, Hartshorne G, Cavilla J, Taylor J, Gardner J, Wilmut I, Meehan R and Young L. (2004). Non-Conservation of Mammalian Preimplantation Methylation Dynamics. Curr Biol 14(7):R266-7.

  Nathalie Beaujean, Jane Taylor, John Gardner, Ian Wilmut, Richard Meehan and Lorraine Young (2004) Effect of Limited DNA Methylation Reprogramming in the Normal Sheep Embryo on Somatic Cell Nuclear Transfer. Biology of Reproduction 71(1):185-93

  Lorraine E. Young and Nathalie Beaujean. DNA Methylation in the Preimplantation Embryo: The differing stories of the mouse and sheep. Animal Reproduction Science 82-83; 61-78.

February 2007

Submission from Professor Richard Gardner, University of Oxford

  I hope a simple reply to the letter by email is acceptable. I do not support the proposal of the Government regarding chimaeras and hybrids, and am concerned that the term "hybrid" in particular has led to misunderstanding regarding the possible use of animal eggs deprived of their nuclear DNA as a vehicle for research on human therapeutic cloning. Defined biologically, an interspecific hybrid is the product of fertilization of an egg of one species by the sperm of another. By earlier permitting penetration of denuded hamster eggs by human sperm as a test of the fertilizing potential of the latter, the initial stage of development of hybrids has already been sanctioned in the past. Further very short-term production of such hybrids is vital for being able to check the chromosmal normality or otherwise of human sperm in case of suspected male infertility. At present, I can think of no compelling reason to extend the development of such interspecific true hybrids beyond the fertilized egg stage.

  Perhaps the best term for an embryo produced by transplanting human somatic cell nuclei into enucleated animal egg is a "cybrid". Given the dire shortage of human eggs for research into at present inefficient procedures such as therapeutic cloning, this strategy offers the only practical way of carrying such research forward.

  At present, chimaeras offer the only critical way of determining whether embryonic stem cells are normal and thus safe to use therapeutically, given that studies on animal embryonic stem cells have revealed that having a normal set of chromosomes is no guarantee of physiological normality.

  Finally, according to the Human Fertilization and Embryology Act (1990), a licence for research cannot authorise any activity unless it appears to the Authority to be necessary or desirable for a purpose specified in the relevant Regulations of the Act. Moreover, granting of such a licence requires that theAuthority is satisfied that any proposed use of embryos is necessary for the purposes of the research.

  These conditions would seem to provide sufficient safeguard against inappropriate or premature use of such novel techniques and procedures on human material to render the cumbersome process of their interim prohibition through legislation unnecessary.

February 2007

Submission from Dr Daniel Brison, St Mary's Hospital

  Thank you for your letter of 22 February. I do not agree with the current goverment position that creation of hybrids (placing a human nucleus into an animal egg cell) should not be allowed, rather I believe that it should be allowed. If it is not allowed in the first instance, then it is essential that the regulator should have the power to permit this research without recourse to primary legislation. Allowing creation of hybrids and or chimeras for research purposes only is appropriate at this moment in time.

  Although I am not a specialist in the area of oocyte biology or nuclear:cytoplasmic interactions, the reason that I believe this research should be permitted immediately is that I believe that it has the potential to provide a number of important benefits: increasing basic understanding of nuclear-cytoplasmic interactions, increasing the understanding of nuclear reprogramming by the oocyte, and advancing the technology of somatic cell nuclear transfer cloning (SCNT). With respect to this last, I believe that there is much benefit to be gained by using the hybrid system, as this can be regarded as an intermediate step between basic research using animal-only SCNT and human research using human nuclei into human eggs. The former is valuable but limited in that there are basic differences between animal and human oocytes which limit the relevance of animal data to the human, the latter is limited by the supply of human oocytes and ethical concerns over asking women to donate oocytes for this purpose.

  The public clearly have a concern over this research, for two reasons: (1) there is concern that we show respect for the human embryo and (2) there is concern over the prospect of animal human hybrids being produced for reproduction. With respect to (1) we have some precedent for this, in that it is permitted to mix human nuclear material with egg cytoplasm containing mitochondria from another individual and this is not regarded as modifiying the genome of the embryo. By this logic, creating a hybrid zygote containing animal mitochondria should not be regarded as a hybrid at all, but rather an entirely human genome. With respect to (2) we have a precedent as SCNT for humans is allowed for research but not reproduction.

  I believe that it is essential to point out the value of hybrid research, in order to help allay public concerns.

February 2007

Submission from Maureen Wood—University of Aberdeen

  Thank you for contacting me and my apologies for replying so close to the deadline.

  I am not in favour of the proposed legislation.

  I believe that the option to transfer human somatic cell nuclei into animal eggs should be available to researchers, under licence of course. This avenue should not be closed when it offers the possibility of investigating cell reprogramming using readily available animal eggs. Research using human eggs will be necessary too but all options should be explored to minimise the number of human eggs required.

February 2007

Submission from Dr Luca Gianaroli, Societá Italiana Studi di Medicina della Riproduzione (S.I.S.Me.R)

  My position is in favour, in principle, of the UK government proposal.

  Please let me know the follow up of the matter.

February 2007




71   Annex 1. Back

72   Review of the Human Fertilisation and Embryology Act Proposals for revised legislation (including establishment of the Regulatory Authority for Tissue and Embryos) December 2006 (Command Paper 6989). Para 2.85. Back


 
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