House of Commons - Science and Technology

Select Committee on Science and Technology Fifth Report

3 Human-animal chimera or hybrid embryos and research

Chimera and hybrid models in research

27. The term 'human-animal chimera or hybrid embryos' can be applied to a wide range of creations, both in general in relation to the Government proposal and specifically, in relation to the recent research proposals submitted to the HFEA for the creation of cytoplasmic hybrid embryos. Hybrids and chimeras are distinct types of entities. A chimera is composed of a mixture of cells derived from two different individuals, either from the same or different species, whilst a hybrid is an entity in which each cell carries genetic material from two individuals, either from the same or different species.[53]

28. Use of hybrid and chimera animal models in research is both legal and relatively common practice. With specific regard to human-animal hybrids, it is currently lawful (and recognised practice) to insert segments of human chromosomes into animal embryos which are then implanted and bred to create transgenic species, for example, mouse models of human blood disorders[54] or of Down's Syndrome.[55] Table 1 describes a number of hybrid models, including transgenic organisms, how such creations are made and the purposes for which they may be used.

Table 1. Examples of hybrid models used in research

Type Definition How is it made? Example of purpose Example

'True' hybrids Organism created by the mixing of gametes from more than one strain or species Fertilisation To create animals/plants with characteristics of more than one strain or species Mule (donkey-horse hybrid)

Somatic cell hybrids Tissue culture cell containing chromosomes of more than one strain or species Often through fusing two cell types together (in vitro) and selecting for those cells containing DNA from both sources. NB: The term 'somatic' may be misleading since one, or both of the cells could be an embryonic stem cell or germ cell[56] To look for the properties of one cell that alter the properties of the other, or to find which genes lie close to one another on a chromosome[57] Hamster-human hybrid tissue culture cells used to map genes on human chromosomes. So far this has only been done in tissue culture[58]

Cytoplasmic hybrids Cells made of the cytoplasm from one cell and the nucleus of the other.
Cytoplasmic hybrids can be derived from the same species or different strain/species in which case they would be termed 'interspecies/inter-strain cytoplasmic hybrids
Similar to above, but created by fusion or through injection of the nucleus of one cell into the cytoplasm of another cell in which the nucleus has been previously removed. This process is referred to as 'cell nuclear transfer' and may involve somatic or germ cells (as depicted in Figure 2)[59] To make cloned animals or to make embryonic stem cells which are clones of the donor individual[60] 'Dolly' the sheep, other cloned animal species. Therapeutic cloning.[61]

Transgenic animals
NB: transgenic animals are not routinely referred to as 'hybrids' but do contain a mix of DNA
Individual containing DNA introduced from outside so that all of their cells contain the genetic modification Can be created by injecting DNA from one species into a single cell embryo. The resultant creation can then be bred to create a chimera (see below) To study the effect of a gene modification, to produce proteins of interest for biotechnology[62] Transgenic mice e.g. mouse models of human blood disorders[63] and Down's Syndrome[64]

Gene Therapy Introduction of DNA into a number of target cells of recipient DNA is introduced via a fusion agent to selected cells To alleviate genetic disease[65] None in general use but clinical trials for various genetic disorders have been carried out e.g. cystic fibrosis[66]

29. The use of chimera models in research is also relatively widespread and legal under current legislation. The term 'chimera' can be used to describe a number of entities, for example, a species created from two cell types such as a sheep/goat or a duck/quail. With specific regard to human-animal chimeras, current legislation allows for their creation, for example, in implanting human neural cells into mouse brains or spinal cords to test whether they can produce functional nerves.[67] It may also be of interest to note that, technically speaking, human recipients of donor organs, either from a different human or animal (for example, a pig heart valve transplant) could be referred to as a 'chimera'. Table 2 describes a number of chimera models, how they are made and the purposes for which they may be used.

Table 2. Examples of chimera models used in research

Type Definition How is it made? Example of purpose Example

Blastocyst injection or aggregation chimera A chimera containing a mixture of cells throughout its body Mixing pluripotent cells from i) two or more early embryos or ii) embryonic stem cells and an early embryo Research to study the effects of the cell mixture and as a route to the production of transgenic mice[68] Mixing mutant cells (which carry a gene altered by mutation) with wild type ones (the 'normal' form of the cell) to study whether wild type cells can rescue the phenotype (observable traits) of the mutant cells.[69]

Interspecies chimera Chimera containing a mixture of cells from two species Mixing pluripotent cells from i) two or more early embryos or ii) embryonic stem cells and an early embryo Research to study differences in organism development, some researchers have suggested that injecting human embryonic stem cells into a developing animal embryo would enable testing for pluripotency[70] Sheep/goat[71] and Duck/quail chimeras[72]

Transplant recipient Individual that has received cells or organ (s) from another individual, either the same or another species Transplantation of cells or organ(s) from one individual to another Used in: i) medicine for replacement of damaged organs or tissues[73]; ii) clinical research to test the properties of cells including human embryonic stem cells[74]; and iii) for testing of stem cell lines[75] i) human bone marrow or pig heart valve transplant into human[76] ii) to test whether stem cells can alleviate symptoms of Parkinson's disease in mice[77] iii) to determine whether embryonic stem cells can differentiate into different cell types in vivo, as demonstrated through the creation of human embryonic stem cell derived tumours in mice[78]

30. Within this extensive catalogue of models for research, a number of creations which may be directly termed 'human-animal chimera or hybrid embryos' are found. For example, the initial entity required for creation of a transgenic animal, in which DNA from a human is injected into a single cell mouse embryo is a human-animal hybrid embryo .[79]

CYTOPLASMIC HYBRID EMBRYOS

31. Cytoplasmic hybrid embryos are created through the transfer of genetic material from one cell, for example, a human skin cell, into an oocyte (egg) from which the main source of genetic material has been previously removed. This process, which is termed somatic cell nuclear transfer (SCNT), can occur through direct transfer of the nucleus from a human cell, as illustrated by figure 2, or through fusion of a somatic cell with the recipient oocyte. In the case of the applications from King's College London and Newcastle University, it is proposed that animal oocytes should be used. These animal eggs will have had their nuclear genetic material previously removed and are hence referred to as 'enucleated animal ova'.

Figure 2: Schematic diagram to illustrate somatic cell transfer of human genetic material into enucleated animal ova.

Are they human?

32. There has been debate over whether human-animal chimera or hybrid embryos, including cytoplasmic hybrid embryos, should be considered 'human'. This is important for the purposes of current regulation, as discussed in the following chapter. However, the question of what it means to be 'human' goes beyond legal definitions to reach some of the ethical and moral objections to this area of research. For example, the Scottish Council on Human Bioethics (SCHB) told us that "in crossing the species barrier, the general understanding of what it means to be a human person would no longer be clear cut".[80]

33. To understand what it means to be 'human' is a complex process since whether or not something is human may be described in a number of ways by different bodies. In scientific terms, how 'human' an entity is could perhaps be described through determination of its percentage of human genetic material. Scientists have shown that humans are 96 per cent similar to chimpanzees,[81] whilst genetic similarity between humans and rabbits, based on gene comparisons, is around 80 per cent.[82] Theological and philosophical arguments may also be used to determine whether or not a creation is 'human'. For example, as we heard from the Rt Revd Lord Harries of Pentregarth during our recent public seminar, questions may be asked regarding whether or not a creation is able to fulfil human attributes such as thinking or feeling. There are clearly many views on what it means to be 'human'. It is right that the Government should take account of the views of representatives from a range of communities, for example scientists, theologians and philosophers, to help develop a better understanding of what a 'human embryo' represents and to ensure that these views are taken into account when proposing revised legislation in this area.

Ethical and moral points of view

34. Whether or not the creation of human-animal chimera or hybrid embryos in research should be allowed has been the subject of much debate. Ethical and moral views surrounding this research area generally feature either within arguments for and against research using human embryos (for example, in the destruction of human embryos for research) or in arguments for and against the mixing of human and animal material (for example, in the formation of human-animal embryos). In very broad terms, the main arguments for and against the creation of human and human-animal embryos can be divided into three categories: arguments which take into account potential violation of human rights; arguments which centre on the value of the research; and arguments which consider the impact of such research on human dignity.

35. There is an argument that this research cannot be against human rights on the assumption that the embryos would not become/are not intended to become human, and hence no human 'rights' could be violated. The argument can also be given that this research should be actively encouraged since such research promotes human rights through the development of treatments and thus enhances human capability. However, once the intention to create a viable embryo is demonstrated, it could be argued that this research is against human rights; for example, if it were ever to be suggested that an embryo should be created and allowed to go to term from a diseased cell line, which would limit the capability of the resultant human.

36. There is an argument that the value of this research depends on its utility. Arguments within this school of thought centre on weighing up the potential value of a technology (for example, in this case for the eventual treatment of disease), with the reasons for not doing so. Arguments within this category may also take into account the 'slippery slope': i.e. some may argue that whilst they accept the creation of human-animal chimera or hybrid embryos for their immediate purpose (to produce embryonic stem cell lines), there are concerns at what may follow: perhaps in this case, that allowing scientists to create human-animal chimera or hybrid embryos may eventually result in the birth of such creations.

37. There is also an argument that research of this nature compromises human dignity, and it is this argument which has formed the basis for much of the opposition evidence we have received in this inquiry. For example, we heard from the Scottish Council on Human Bioethics (SCHB) that "the creation of certain kinds of human-nonhuman embryonic combinations could seriously undermine the whole concept of human dignity".[83] However, what is meant by the phrase human 'dignity' is vague. Professor Raanon Gillon told us that "the concept of human dignity is a very complex one and people have different accounts of what they mean by it".[84] The SCHB told us that "in this regard, it should be remembered that the concept of human dignity is not a scientific one. No individual will ever be able to prove whether or not a person possesses human dignity".[85] Human Genetics Alert (HGA) is also against the creation of human-animal chimera or hybrid embryos because they feel that "the strong public concern about the unnaturalness of creating human/animal hybrids is valid and must not be ignored",[86] an argument which generally fits into the dignitarian approach.

38. With respect to memoranda received by this inquiry detailing ethical and moral concerns about the creation of human-animal chimera and hybrid embryos for research, we have found that, in some cases, opposition appears to be specific to the mixing of human and animal material, whilst in others, such opposition relates to all research using human embryos. Establishing where there is specific opposition to the creation of human-animal chimera or hybrid embryos for research purposes is important if an accurate assessment is to be made of whether there is significant opposition to this research from those who, like the Government, otherwise support human embryo research. As the Minister, Caroline Flint MP, told us "if you are having a discussion and people are fundamentally opposed to something … any variation is linked to their fundamental opposition" and "there is not much room for debate in that".[87]

39. We have received evidence in which opposition to the mixing of human and animal material appeared to stem directly from general opposition to the use of human embryos in research. For example, the watchdog group, Human Genetics Alert (HGA) opposes "the creation of embryos purely for purposes of research",[88] and Dr Stephen Brennan, Master of the Guild of Catholic Doctors, told us that "human life is sacred and should not be used in this way".[89] In addition, we heard from the public interest group Comment on Reproductive Ethics (CORE) which is opposed to the creation of human-animal chimera or hybrid embryos for research, at least at present, and reiterated its opposition to destructive [human] embryo research.[90] We have also received evidence from the Linacre Centre for Healthcare Ethics which is "opposed to all research involving a lethal attack on a human moral subject, of any age or stage of development".[91]

40. We have also heard from a number of parties who are specifically against the mixing of human and animal genetic material, not all of whom are clearly opposed to research with human embryos, although since this question was not posed in our call for evidence, it is impossible to be sure. Donald Bruce of the Church of Scotland Church and Society Council told us that whilst the Society believes that research "should not be allowed that involves the mixing of animal and human reproductive cells to create an embryo-like entity", this does not "spring from a rejection of all research on the human embryo".[92] The Church of England takes a similar view.[93]

41. Defining views clearly in an area such as this is essential. To date the most extensive study of public opinion in this area stems from the Government's 2005 public consultation on review of the HFE Act. In order to ascertain whether there was strength of opinion specifically against the creation of human-animal chimera or hybrid embryos, we asked the Minister for a breakdown of the responses. We were told that of the 336 responses that specifically addressed the question of whether or not the creation of human-animal chimera or hybrid embryos should be allowed, 277 were opposed. It is worth noting that included in the 59 other responses, most of which were in support of research using hybrid and chimera embryos, were responses that represented the collective views of multiple membership organisations. The Minister went on to explain that the consultation document did not seek views on embryo research per se, as "the Government had made clear its intention not to propose changes to the fundamental aspects of the current law, including the permissibility of embryo research". However, 227 of the respondents opposed to hybrids and chimeras also stated opposition to human embryo research, or such opposition may reasonably be inferred.[94] We regret that the Department of Health did not seek to specify more clearly in its consultation what views it was seeking, nor to evaluate fully the responses of the public consultation exercise. We recommend that in future a more systematic statistical or scientific approach is developed to quantify and qualify the results of public consultation.

42. We take the ethical and moral concerns with respect to work of this nature very seriously and we are in full agreement with Dr David Jones and colleagues of St Mary's University College London who told us that "in a democratic society, ethical and moral arguments both secular and religious should be considered".[95] Indeed, we fundamentally believe that such views have an important role in the debate regarding whether or not the creation of human-animal chimera or hybrid embryos should be allowed for research in the UK and that they must be taken into full account when drafting legislation, particularly in areas of research such as this. We recognise the sincere ethical and moral concerns associated with research of this nature and are therefore concerned that, to respond to these concerns, any regulatory framework associated with use of human-animal chimera or hybrid embryos in research should be transparent and workable.

43. We have, however, been concerned to note that, in certain cases, the serious ethical and moral objections to work of this nature have been clouded through the raising of what appear at first sight to be scientific arguments to support such opposition but which do not stand up to scrutiny. Some of the opposition in responses which we received was based on hostility to science as against Nature. In addition, some throwaway statements concerning the scientific basis for proposed areas of research not only lack supporting evidence but may perhaps be better termed 'pseudo-science'. We are of the opinion that ethical and moral concerns should be considered within the context in which they are made, and that inappropriate use of science to justify ethical and moral arguments is unhelpful. Inappropriate use of science should be identified and disregarded by Government and other policy-makers.

44. In this context, we draw attention to the recommendation of the previous Science and Technology Select Committee that there is a need for a new Parliamentary standing Committee on Bioethics. This Committee would "undertake annual scrutiny of the Regulatory Agency for Fertility and Tissues, make recommendations on the need to amend or introduce new legislation and scrutinise draft legislation brought before Parliament within its remit".[96] In line with the recommendation of the previous Science and Technology Committee, we recommend the creation of a new Parliamentary standing Committee on Bioethics.

Is it necessary to use hybrid and chimera embryos in research?

Use of human embryos

45. Under the HFE Act, the HFEA may only grant licences where the activity authorised by the licence is necessary or desirable for the purposes detailed in paragraph 13 above, including that such research is aimed at increasing knowledge about the development of embryos; increasing knowledge about serious disease or that the research will enable any such knowledge to be applied in developing treatment for serious disease.[97] In addition, the HFEA will not grant a licence using a human embryo unless it is fully satisfied that the use of human embryos is necessary for the purposes of the research.[98]

PROGRESS IN STEM CELL RESEARCH

46. As previously discussed (paragraph 12), the HFE Act allows for the production of stem cells through therapeutic cloning using available human oocytes (eggs).[99] The recently submitted licence applications, from King's College London and Newcastle University, also request permission from the HFEA to derive stem cells from human-animal cytoplasmic hybrid embryos. The researchers want to use this methodology to enable them to produce lines of stem cells which are specific to patients with genetic diseases and to learn about how cells can be reprogrammed to become different cell types.[100] Production of stem cell lines through this method involves taking a somatic cell (e.g. a skin cell) from an affected patient and transferring its genetic material into an animal egg which has previously had its own genetic material removed, that is a cytoplasmic hybrid embryo, created by somatic cell nuclear transfer as described by Figure 2.[101] The newly created hybrid embryo is then allowed to develop until the blastocyst stage at which point embryonic stem cells can be removed.

47. The stem cells may have several purposes. In the first instance, it is hoped by many that production of stem cells from cytoplasmic hybrid embryos may contribute toward the development of treatments of diseases studied. For example, the Cystic Fibrosis Trust recognised "the important potential benefit to human health from being able to grow stem cells with specific genetic abnormalities, such as Cystic Fibrosis, improving the efficiency of therapeutic cloning techniques and establishing cell lines for the testing of new treatment".[102] Cancer Research UK highlighted that "future stem cell research could also uncover ways of improving outcomes after treatment for cancer, potentially providing us with the ability to regenerate or replace normal tissue following surgical removal of cancerous tissue, or its destruction by chemotherapy or radiotherapy".[103] The Multiple Sclerosis and Alzheimer's Societies also argued that such technologies show "great potential as laboratory tools to explore early processes that lead to neurological conditions".[104]

48. Secondly, stem cells produced through somatic cell nuclear transfer may also be useful in drug discovery and are a potential replacement for animal use, for example in some toxicity testing. Recommendation 1 of the UK Stem Cell Initiative, set up by the Government, identified disease-specific stem cell lines as an important contribution to drug discovery and as potential alternatives to animal testing.[105] The Muscular Dystrophy Campaign has told us that "stem cells could be used as a source of pure populations of human cells to be used in drug testing". The Campaign argued that "the use of animals for the toxicity testing of new drugs does not always highlight potential problems so using these populations of cells, high throughput drug screens could be designed to screen drug effects in specific human cell types especially those that may be vulnerable to toxicity or those that form the drug's target tissue".[106] The Institute of Biology also considered that stem cells produced through somatic cell nuclear transfer "should reduce the need for research on live animals as models for certain diseases".[107]

49. Additional reasons for the creation of cytoplasmic hybrid embryos include increasing knowledge about cell reprogramming. Whilst each cell contains all of the genetic material needed to build a completely new organism, different cells express only the genes necessary for the function required within the tissue or organ in which they are based.[108] If stem cells are to be of use as treatments of disease, increased knowledge about how these cells are directed into different cell types, and how they might be 'reprogrammed' is desirable. Dr Lyle Armstrong of Newcastle University told us that if we can understand how the reprogramming process occurs in cytoplasmic hybrid embryos, "we might be able to reproduce it" and that "the possible implications of such understanding are great indeed".[109]

ANIMAL EGGS AS A REPLACEMENT FOR HUMAN EGGS

50. Use of human eggs for research into stem cells is legal under licence from the HFEA. However, such research practice requires large numbers of human eggs, availability of which is limited.[110] Use of human eggs for research has also raised concerns about whether it is appropriate to encourage women to undergo an invasive and potentially harmful procedure, such as is required for the collection of eggs, without any direct medical benefit to the donor.[111] It has therefore been argued, for example by the Cystic Fibrosis Foundation, that by allowing insertion of animal eggs with human genetic material, researchers could potentially increase the number of stem cell lines available for research,[112] far in excess of those which would be available from human eggs alone.

51. An extremely large number of eggs is also claimed as essential for the development of the practical techniques which will be necessary for the eventual production of embryonic stem cell-based therapies from human embryos and eggs (through therapeutic cloning). Currently, the efficiency of production of embryonic stem cells through somatic cell nuclear transfer is low. Dr Lyle Armstrong of Newcastle University told us that "we would need in excess of 30 oocytes [eggs] to have a reasonable chance of producing an ESC [embryonic stem cell] line for each patient".[113] We also heard from Dr Stephen Minger at King's College London that "until the efficiency of successful SCNT [somatic cell nuclear transfer] in humans can be increased significantly (to perhaps 10-20%) alternative sources of oocytes specifically for SCNT are needed".[114] It has therefore been suggested, for example by the BioIndustry Association (BIA), that use of animal eggs should be allowed to enable researchers to develop the techniques required for the production of stem cells.[115]

Potential problems with this research

Mixing animal and human material

52. We have received submissions which suggest a number of risks potentially associated with work involving the mixing of human and animal material. The Scottish Council on Human Bioethics (SCHB) believes that by undertaking such work, scientists risk creating new diseases. They told us that it is "well known that many animals may harbour in their organs, cells and genome, microbiological and other entities which may cross the species barrier and develop in the host",[116] for example, Creutzfeldt-Jakob disease. This view is supported by Christian Action Research and Education (CARE) who wrote of the "real risk of disease transmission from viruses crossing the species barrier and developing in the host".[117]

53. The SCHB has also claimed that human-animal chimera or hybrid embryos may be subject to a greater number of developmental problems,[118] presumably limiting their effectiveness as models in research. A similar view was expressed by Peter McCullagh, an Australian expert, who believes that data produced from human-animal chimera or hybrid embryos will be of little use. Mr McCullagh explained that, given the complete lack of knowledge of how the development and function of the human/animal entity will resemble that of either contributing species, "the experimental data will predictably be quite uninterpretable" and that "the potential of an experiment, in any discipline, to add to the sum of knowledge is only as good as its capacity for interpretation".[119]

54. We recognise the scientific concerns associated with research of this nature. In the event that research using cytoplasmic hybrid embryos is authorised, we urge the Government to ensure that appropriate risk management procedures are established and implemented. Such procedures should complement those already in existence for working with human and animal material. In addition, we recognise concerns that data from human-animal chimera or hybrid embryos may be uninterpretable or of limited use. However, without the production of such data in the first instance, we find it difficult to comprehend how such claims can be realised. We recognise that issues such as data viability and interpretation would be considered during scientific peer review of any applications for research in areas such as this.

SPECIFIC PROBLEMS POTENTIALLY ASSOCIATED WITH CYTOPLASMIC HYBRID EMBRYOS

55. Whilst, as discussed previously, it is claimed that the creation of cytoplasmic hybrid embryos using animal oocytes is necessary, for example, for stem cell research, there is limited experience that this methodology will work. A team led by Professor Hui Z Sheng in China has successfully derived embryonic stem cells by the transfer of human somatic nuclei into rabbit oocytes. Further work was then carried out to show that the derived embryonic stem cells were human, for example based on studies to determine karyotype (the chromosomal characteristics of a cell), and that they have the ability to differentiate into different cell types.[120] There has been some disagreement over this work. Although Professor Sheng's team announced that it was generating stem cells by transferring nuclei from human skin into rabbit eggs (somatic cell nuclear transfer into enucleated rabbit ova) in 2001, the research was not published until 2003, when Cell Research, a peer-reviewed journal accepted it. That it took such a long time to publish the work is believed to result from a lack of conviction in the scientific community that the research had been successful. Scientists reported as concerned about Professor Sheng's work include Doug Melton, a cell biologist at Harvard University who, although believing that cells were produced, has said that "it would be very surprising if the cell lines were stable".[121] Rudolf Jaenisch, of the Whitehead Institute in Cambridge, Massachusetts, was also not convinced that the derived cells meet the usual criteria for embryonic stem cells. He has said that "an important criterion is indefinite growth", and that "this is not shown".[122] However, it should be noted that all the scientists to whom the Committee has spoken during this inquiry were fully supportive of Professor Sheng's work.

56. Other scientific objections to the somatic cell nuclear transfer of human genetic material into enucleated animal ova for creation of human-animal cytoplasmic hybrid embryos came from Human Genetics Alert (HGA), which believes that the proposed experiments are of "little scientific value" since there is limited likelihood that embryonic stem cells will be obtained.[123] Furthermore, HGA is of the opinion that embryonic stem cell lines derived from human-animal chimera or hybrid embryos will be abnormal since "it is almost certain that they will contain subtle abnormalities in gene expression which will invalidate any experimental results obtained with them".[124] Professor Lorraine Young of Nottingham University also argued against the usefulness of the creation of cytoplasmic hybrid embryos, since her research has demonstrated that the DNA of eggs and sperm restructures after fertilisation of the egg and that some of the same restructuring applies to somatic cells after somatic cell nuclear transfer, and that "considerable species differences exist in this process".[125]

Mitochondria and mixed mitochondrial DNA

57. During this inquiry we also received evidence to suggest the effects of mitochondrial DNA on embryonic stem cells produced from cytoplasmic hybrid embryos. Animal eggs, as with all eukaryotic cells (which contain a nucleus and other membrane-bound organelles), have populations of mitochondria. Mitochondria produce the energy required to drive cellular processes and possess their own small genome which is known as mitochondrial DNA (mtDNA). In reference to the essential role of mitochondria in energy production, it is logical that mitochondrial defects can have serious implications, as is demonstrated by mitochondrial-based diseases, such as Lebers hereditary optic atrophy which causes degeneration of the optic nerves and retina.[126] According to Dr Justin St John from Birmingham University, "nuclear transfer can result in mixed populations of mtDNA being present in embryos".[127] Christian Action Research and Education (CARE) pointed out that "it is not fully understood" what effect this may have on cytoplasmic hybrid embryos.[128] However, rather than deem this a reason not to conduct such research, Dr St. John believes that the creation of human-animal chimera or hybrid embryos may actually "offer us the opportunity to elucidate some of the causes of mitochondrial DNA disease" and that "not to allow this work to go ahead would considerably disadvantage experimental work in these fields".[129] Research, by its very nature, is aimed at enhancing knowledge. Whilst we recognise scientific debate about the potential usefulness of cytoplasmic hybrid embryos in research, we do not believe that the existence of differing views of whether a methodology is workable before it has been sufficiently tested is reason enough to prohibit such research from taking place.

Scientific opposition to research involving hybrid and chimera embryos

58. In order to determine whether there may be additional scientific problems associated with research of this nature, we were keen to hear opposition to the creation of human-animal chimera or hybrid embryos from scientists and experts in either stem cell research or embryology. We received no such views in response to our initial call for evidence. The Minister in her letter to The Observer of 21 January 2007, referred to the lack of "a firm consensus within the scientific community about precisely which human-animal creations should be allowed, any immediate imperative for doing so, or the availability and interpretation of supporting evidence",[130] and the HFEA made a similar reference in announcing its consultation.[131] To track down evidence of this lack of consensus, we contacted experts who had not already contributed to this inquiry and who attended a meeting at the HFEA in November 2006 to discuss this area, to ask them if they believed that current Government proposals to prohibit the creation of human-animal chimera or hybrid embryos for research were appropriate. While there was clearly debate about the likelihood of the method working or producing useful results, support for the Government proposals was extremely limited, and many of those responses focused specifically on the creation of cytoplasmic hybrid embryos. We recognise the scientific debate among experts about the potential usefulness of the research under discussion in this Report but we conclude that the scientific community as a whole is supportive of the work being licensable, even where there may be doubts about its likely success.

Conclusions on the desirability and necessity of hybrid and chimera embryo research

59. The strength of support for production of stem cells via this methodology has convinced us that this technique is both necessary and desirable as detailed by current HFEA conditions for use of human embryos in research.[132] We believe that the creation of human-animal chimera or hybrid embryos, and specifically cytoplasmic hybrid embryos, is necessary, for example in the pursuit of knowledge about the genetic basis of disease and the direction of stem cells into future cell-based therapy. Furthermore, we recognise that stem cells produced through this methodology may be useful in drug discovery and that they may lead to the eventual reduction of animal use, for example in toxicity testing.

60. We are convinced of the need to use animal eggs in the creation of cytoplasmic hybrid embryos for the derivation of stem cells. We believe that use of animal eggs in the creation of cytoplasmic hybrid embryos will help to overcome the current shortage of human eggs available for research and that use of animal eggs is required to enable researchers to develop the practical techniques which may be required for eventual production of cell-based therapy through this method using human eggs.

53 Ev 67 Back

54 Wallace, H.A.C., Marques-Kranc, F., Richardson, M., Luna-Crespo, F., Sharpe, J.A., Hughes, J., Wood, W.G., Higgs, G.R. and Smith, A.J.H. Manipulating the mouse genome to engineer precise functional syntenic replacements with human sequence. Cell (2007) 128: 197-209. Back

55 Public Health Genetics Unit, www.phgu.org.uk/ecard?link_ID=1427 Back

56 Ev 69 Back

57 Ibid Back

58 Ev 69 Back

59 http://en.wikipedia.org/wiki/Somatic_cell_nuclear_transfer Back

60 Ibid Back

61 Campbell KH, McWhir J, Ritchie WA, Wilmut I. Sheep cloned by nuclear transfer from a cultured cell line, Nature, 1996 Mar 7;380(6569):64-6. Back

62 Expression of Human Anti-Hemophilic Factor IX in the Milk of Transgenic Sheep. A. J. Clark, et al. (1989) Bio/Technology7, 487 Back

63 Wallace, H.A.C., Marques-Kranc, F., Richardson, M., Luna-Crespo, F., Sharpe, J.A., Hughes, J., Wood, W.G., Higgs, G.R. and Smith, A.J.H. Manipulating the mouse genome to engineer precise functional synthetic replacements with human sequence, Cell (2007) 128: 197-209. Back

64 Public Health Genetics Unit, www.phgu.org.uk/ecard?link_ID=1427 Back