House of Commons - Science and Technology

Select Committee on Science and Technology Fifth Report

5 Future regulation of research involving the creation of human-animal chimera or hybrid embryos

78. As previously indicated, embryo research is currently regulated under the HFE Act (paragraph 12), and through case law (paragraph 62). However, embryo research has progressed significantly since the creation of the original HFE Act in 1990 and calls for revised legislation have been made, including from the HFEA[187] and the previous Science and Technology Committee.[188] We are therefore supportive of the Government's intention, highlighted in its review of the Human Fertilisation and Embryology Act 1990, that "revised legislation will clarify the extent to which the law and regulation applies to embryos containing human and animal material".[189] We agree that there is a need for revised legislation, decided by Parliament, to regulate for current developments in the creation of human-animal hybrid and chimera embryos and to provide a future framework under which regulatory authorities can operate.

79. The Government has announced its intention to present a draft Bill, expected in May 2007, for pre-legislative scrutiny.[190] During oral evidence to the Committee, Caroline Flint MP, the Minister of State for Public Health, told us that with the "number of issues" that the review of the HFE Act covers, "it is important to have this pre-legislative scrutiny".[191] This will be welcome as adding to the debate in this area. The HFEA consultation will feed into the process, according to Ms Harrison who told us that HFEA "will share the results of our consultation and our evidence gathering with the department and hope that it informs the pre-legislative scrutiny stage".[192] We also intend our own Report to make a significant contribution to the process in this area. We support the Government's intention for pre-legislative scrutiny of the draft Bill and encourage the Government to take advantage of all possible sources, including this Report and that of our predecessor Committee, to inform the debate.

Definitions and terminology in the draft Bill

80. Throughout this inquiry we have battled to develop a clear understanding of what the Government means by its use of the term 'hybrid and chimera embryos'.[193] It has become clear as we have progressed that, in some cases, individuals interpret the Government proposals as exclusive to the creation of cytoplasmic hybrid embryos. For example, Professor Lorraine Young, when asked whether she supported the Government proposals, referred only to the creation of cytoplasmic hybrid embryos.[194] In fact, the memoranda submitted into this inquiry indicate that many respondents have interpreted the Government proposals in this way,[195] perhaps as a result of the significant media coverage of the research applications from King's College London and Newcastle University immediately prior to our inquiry.[196]

81. However, other respondents to our call for evidence interpreted the Government proposal as inclusive of a wider range of creations. Some of these witnesses are concerned about the potential wider implications for prohibition with the terminology currently used. Dr Stephen Minger of King's College London urged us to consider carefully what the consequences of a ban on creating "hybrids" or "chimera" would entail, citing the creation of transgenic mice and telling us that "the commercial and academic scientific community have generated over 20,000 strains of mice and rats which contain human disease genetic material, and many of these are important research tools for developing new therapies against cancer and other important human diseases".[197]

82. We are concerned that there is discrepancy between the understanding of scientists and Government in the terminology used. Dr Lyle Armstrong of Newcastle University told us that "a hybrid is essentially an organism which is formed by the mixing of the chromosomes of two separate organisms".[198] As detailed in Chapter 3, the term 'hybrid' can be used to encompass a range of creations from cytoplasmic hybrid embryos to transgenic models of Down's Syndrome. It is therefore a matter of concern that the Minister's definition of a human hybrid was offered simply as an entity "formed by fertilisation of a human egg by an animal sperm".[199] Similarly, on chimeras, Ms Flint told us that "in terms of a human chimera we have used the formation of a chimera by taking a human embryo and adding animal cells".[200] Dr Armstrong, on the other hand, defined "a chimera is essentially an organism which is formed by the mixing of the cell types from two separate organisms".[201] This may seem a subtle difference perhaps, but Dr Armstrong's definition covers a range of useful research tools, such as the formation of blastocyst or aggregation chimera used as a route to the production of transgenic mice (as detailed in table 2, chapter 3), which would not be included in the Minister's understanding of the terminology but which might be covered in the proposed legislation.

83. The Minister has acknowledged difficulties in regard of the terminology used within the Government proposals. She told us that "what this debate we are having has shone a light on is the different interpretations of what is meant by a hybrid or a chimera".[202] Later, she clarified that the terminology used in the review was based on that used in previous reviews and reports, and that it was intended to cover the following:

mixing of human and non-human gametes;
embryos resulting from combination of haploid sets of human and animal chromosomes;
embryos created by placing a human cell or cell nucleus in an enucleated animal egg;
fusing of a human embryo with animal cells and;
creation of a "transgenic" human embryo (e.g. by addition of a non-human gene or genes).[203]

84. The Minister's supplementary evidence provided clarification that the scope of the legislation was not intended to extend to entities such as required in the creation of transgenic mice (for example, those currently used in the study of Down's Syndrome.[204] Whilst we appreciate that Ms Flint may have intended that the terminology used in the White Paper should refer to the creations she has detailed above, this has only been established in response to our inquiry and we find it difficult to understand why this was not explicitly stated at time of its publication. We remain unconvinced that the Government fully understood the scope and implications of its proposals at publication.

85. The difficulties of definition have long been recognized, including by our predecessors in the last Parliament who, for want of better guidance, used the definitions enshrined in Canadian law.[205] The Academy of Medical Sciences in the UK has recently launched a study which aims to:

i. agree definitions of embryos combining genetic material from more than one individual, particularly those combining human and non-human material;

ii. identify relevant research protocols;

iii. identify key opportunities for research using such embryos, and cells derived from them, together with an assessment of how these opportunities are balanced by safety and ethical concerns; and

iv. to provide recommendations to Government to further inform revised legislation in this area.[206]

We are critical of the Government for not clearly setting out areas of research practice intended to fall under the proposed legislation. Much confusion has thus been caused. However, we accept that this lack of clarity may result from the lack of understanding more generally with regard to the potential for this area of research and what the term 'human-animal chimera or hybrid embryos' may cover. We welcome moves by the Academy of Medical Sciences to address this problem and we urge the Government to work with the Academy, HFEA and other stakeholders to ensure that the scope of research practice intended to be covered by legislation is clearly defined in the draft Bill.

The proposed prohibition

86. The Government has proposed that the creation of human-animal chimera or hybrid embryos in vitro should not be allowed in the first instance, but that the law should contain a power enabling regulations to set out circumstances in which the creation of hybrid and chimera embryos in vitro may be allowed in the future. This two-step approach has been widely interpreted - both by opponents and supporters of the policy - as a prohibitive one.

87. The proposal has met with significant opposition, including from within Government, research funders and the regulator itself. The Department for Trade and Industry, responsible for the support of UK science and technology, told us that it "supports the view that, with appropriate regulation, the creation of hybrid stem cells for research purposes should be permitted".[207] We also heard from Professor Colin Blakemore, Chief Executive of the Medical Research Council (MRC), that he hopes for "permissive legislation, in which areas of research that are not considered to be acceptable necessarily might not be allowed, but the generality would be".[208] The position of the HFEA, which is responsible for regulating this area of research, has remained quite clear throughout: it "would like to see this research permitted within the usual restrictions, within the usual controls".[209] This view is supported by scientists, such as Dr Robin Lovell-Badge of the National Institute for Medical Research (NIMR), who argued that "it is far better to control such research activities under a good regulatory system through careful consideration of proposed experiments by scientific and ethical review panels, than it is by prohibitive laws that are likely to be both too restrictive and leave dangerous loopholes, especially in this rapidly advancing field of science".[210] Even the Prime Minister was recently quoted in The Times as saying that the Government was "not dead set" against the King's College London and Newcastle experiments, "in fact the opposite", and whilst "there were difficult issues surrounding creating the embryos", he added that "I'm sure that research that's really going to save lives and improve the quality of life will be able to go forward".[211]

88. In the face of this broad spectrum of opposition, the Minister claimed that her policy had been misrepresented and that her real intention was to 'leave the door open' to such areas of research. Caroline Flint told us that "we are actually proposing a liberalisation of where we are now".[212] When pressed on how banning an area of science could be seen as a 'liberalisation', Ms Flint told us that "we are not banning science and that is very clear in the White Paper".[213] She added that "we have not shut the door, in fact we have moved further forward than we have ever been before in this particular area of science"[214] and that "the White Paper makes it absolutely clear that we think there needs to be a door open to be able to deal with these processes and how they develop".[215] Given that a prohibition will ban research that the HFEA - the Government's own advisor - feels is probably licensable and believes should be permitted, we believe that the Government's proposals are indeed prohibitive. Even if that were not the case, we find it astounding that the Minister could have allowed such misinterpretation to take so strong a hold in all sections of the community to the extent that none of the evidence received by our inquiry, either for or against the proposals, reflects the Minister's own view of the regulatory regime her proposals are intended to create. We find the Government proposals in the White Paper unnecessarily prohibitive and recommend the Government ensure that its draft Bill reflects the liberal view it claims to be taking in opening the door to research using human-animal chimera or hybrid embryos.

ALLOWING FOR SUCH RESEARCH IN THE FUTURE

89. The Minister's claims for her policy to be regarded as permissive rest upon the inclusion within the White Paper of the proposal that the law should contain a power enabling regulation of the creation of human-animal chimera or hybrid embryos in the future. This claim is rather undermined by the Department of Health's admission that the "Government has not taken a view on whether or when such regulations may be made".[216] In other words, there are no plans to allow any such work, however defined, immediately or in the foreseeable future. We note that the process of making regulations would necessarily involve a considerable length of time, once a decision had been taken by the Government to utilise this power in any given circumstance.

90. The North East Stem Cell Institute (NESCI) took "issue" with the wording of the White Paper, which proposes an outright ban on the creation of hybrid embryos, but then indicates in "very vague terms" the possibility that their creation may be permitted by further legislation in the future for research purposes.[217] It explained that "not only does this cause confusion, but it comes across as a strategy to appease public concern whilst not totally closing the door on what is clearly recognised as exciting and useful science" and that "this approach would simply delay the inevitable debate that will need to be had".[218] We agree. It makes no sense to delay research which is needed immediately, as detailed previously (for example, paragraphs 59 and 77) and which the Government accepts has the potential to "offer huge benefits".[219] We believe that there is a need to allow research using some forms of human-animal chimera or hybrid embryos, including but not exclusively cytoplasmic hybrid embryos, to proceed immediately. We recommend that the Government propose draft legislation which is immediately permissive, through regulation, to those areas of research it deems acceptable.

Drawing the line: acceptable research practice

91. Whilst we are of the opinion that the creation of human-animal chimera or hybrid embryos should be allowed for research, we believe that such research should be tightly regulated to ensure that only legal and appropriate research practice is allowed. Clear regulation in terms of what may and may not be permissible is necessary, for example in alleviating possible public fear that research of this nature may lead to the creation of half animal-half humans. As Sir Liam Donaldson, the Chief Medical Officer, told us, "some people might have a problem" with the concept of a hybrid in which human sperm were mixed with animal eggs.[220] We agree, and we therefore consider it useful for a line to be drawn between what is and is not acceptable.

THE 14-DAY RULE

92. One consideration is the length of time for which such entities may need to be allowed to develop. Currently, under the HFE Act, whilst the creation of a human embryo is licensable for research, the licence cannot authorise "keeping or using an embryo after the appearance of the primitive streak".[221]The primitive streak is to be taken to have appeared in an embryo not later than the end of the period of 14 days beginning with the day when the gametes are mixed, not counting any time during which the embryo is stored.[222]

93. In the inquiry in the last Parliament into Human Reproductive Technologies and the Law, the Committee found no benefit in keeping human-animal chimera or hybrids for longer than the 14-day limit imposed upon embryos consisting of only human material.[223] We deemed it important to establish during this inquiry that this was still the case. Dr Stephen Minger of King's College London told us, with specific reference to cytoplasmic hybrid embryos, that he "can see no reason for culturing the embryo beyond the 14 day limit as set out in the HFE Act".[224]Other experts agreed. Dr Robin Lovell-Badge at the National Institute for Medical Research did not "see any need to take them [cytoplasmic hybrid embryos] past the 14th day" and saw "no reason" to take human-animal chimera embryos, more generally, beyond 14 days in vitro. Again, Professor Ian Wilmut of the University of Edinburgh did not "envisage a benefit" in keeping the embryos beyond day 14. Professor Wilmut expanded this view, telling us that "in the great majority of studies the period of culture would be for 6 or 7 days" since, in the case of cytoplasmic hybrid embryos, this "is sufficient time for the embryo to reach the stage from which stem cells may be derived".[225] We believe that, in general, the creation of all types of human-animal chimera or hybrid embryos should be allowed for research purposes, if appropriately regulated. However, in line with the recommendation of the previous Committee, we see no benefit from allowing the development of human-animal chimera or hybrid embryos past the 14 day stage in vitro and recommend that such practice is not licensed unless it is proved necessary.

IMPLANTATION OF HUMAN-ANIMAL CHIMERA OR HYBRID EMBRYOS INTO A WOMAN

94. The HFEA Act 1990 states that "no person shall place in a woman a live embryo other than a human embryo".[226] We have received no evidence during this inquiry to suggest that such practice would be beneficial or desirable or that researchers would like to attempt such experiments. In line with the recommendations of the previous Science and Technology Committee, we recommend that legislation prohibit the implantation of human-animal chimera or hybrid embryos in a woman.

INJECTING CELLS DERIVED FROM HUMAN-ANIMAL CHIMERA AND HYBRID EMBRYOS INTO ANIMAL MODELS

95. Some scientists also identify a need to inject cells derived from human-animal chimera or hybrid embryos into animal models. These experiments may be required to enable researchers to prove that stem cells produced from cytoplasmic hybrid embryos are truly pluripotent, that is that they have the ability to differentiate into different cell types. Such experiments include the 'teratoma assay', which we are told by Dr Robin Lovell-Badge is "a common test of human ES [embryonic stem] cell potential".[227] During this test, researchers inject the cells into a genetically immunocompromised mouse (for example the 'Severe Combined Immunodeficiency Disease [SCID] mouse' which has no protection against infection and cannot reject transplanted tissue) where the cells are likely to form teratomas, tumours which contain many different cell types.[228]

96. We have also heard from Dr Minger that there are other instances where "implantation of human embryonic stem cell-derived populations into experimental animals will be necessary".[229] Dr Minger explained that these could include experiments for "assessing the contribution of stem cells to repair of the damaged spinal cord, and determining the ability of stem cells to integrate into damaged myocardium".[230] At present, such research in the UK is regulated through the Home Office under the Animals (Scientific Procedures) Act 1986, and we agree with Dr Minger that there is little difference between these experiments and "traditional preclinical testing of human cell populations in experimental animals".[231] We believe that this is acceptable research practice. However, the current lack of clarity with regard to what the Government means in its proposals leaves us concerned that the terminology used could be extended to cover research practice currently allowed under the Home Office, despite an assurance from the Minister that this will not be the case.[232] We recommend that care be taken by the Government to ensure that the draft Bill does not prohibit research using human embryonic stem cell lines where such research is currently regulated through the Animals (Scientific Procedures) Act 1986.

DEVELOPMENT OF HUMAN-ANIMAL CHIMERA OR HYBRID EMBRYOS PAST THE 14 DAY LIMIT IN VIVO

97. We have also received evidence to suggest that there are occasions when it may be "useful or desirable" to allow development of certain types of human-animal chimera beyond 14 days in an animal's uterus, and even for the chimeras to be born.[233] Within the evidence we have received, it has been made clear that such techniques are, at present, only thought to be of potential use in further determining pluripotency of stem cell lines, and not in the development of the human-animal chimera or hybrid embryos themselves. We recognize that this is an important distinction. The proposed experiments would involve the introduction of labelled human stem cells, such as may be derived from cytoplasmic hybrid embryos, into the developing blastocyst of an animal. The blastocyst could then be implanted into a surrogate uterus to further determine pluripotency by looking for the presence of marked cells throughout the organs and tissues of the resultant embryo or adult organism.

98. In general, we have found little support for such practice or that there is a need for such research to be currently undertaken. For example, we have heard from Professor Ian Wilmut that he does not know "of any laboratory that envisages inserting human embryo stem cells into an animal blastocyst"[234] and that "it should be emphasised that no studies of this kind are envisaged at present".[235] Dr Minger told us that, for his own experiments he "will rely solely on the use of teratomas and in vitro differentiation to assess pluripotency".[236] Whilst we see no immediate benefit from the implantation of cells (for example, stem cells derived from cytoplasmic hybrid embryos into animal embryos), we consider it important that this door is left open to allow for such research practice, should it become necessary in the future. We recommend that legislation allow for regulation of the implantation of human stem cells, whether created from human embryos or human-animal chimera or hybrid embryos, into animal blastocysts.

Legislative and regulatory structure

99. We have made it clear that we regard the current Government proposals as overly prohibitive and that there should be regulation of this research area through licensing. The new legislative structure should permit the creation of animal-human hybrid and chimera embryos for research purposes, subject to regulation, and should aim to reduce the risk of litigation on borderline cases.

100. Through consultation with the legal services available to us, we have reached the conclusion that it is possible to create a legal framework within which anything which fell into this or a related category would be capable of being licensed, by the HFEA or proposed RATE, for example. On the pattern of the existing HFE Act, this would start with a general prohibition to which exceptions apply through licences awarded by the authority but, unlike the Government proposals, it would be clear that the assumption was that the Authority would consider anything for a licence which was not specifically ruled out. As indicated above, we recommend ruling out keeping embryos beyond 14 days and implantation of the embryo in a woman. Similarly, it would be possible to ensure that specific existing practices or proposals, for example human-animal cytoplasmic hybrid embryos created by somatic cell nuclear transfer, could be included in the new framework as soon as the Bill came into force. Finally, to provide time for the Secretary of State to decide whether to make regulations to ban a novel process, the framework could also contain a provision to enable the Secretary of State to put a stop to the procedure for a limited period while deciding whether or not to make regulations. In each case, the regulations on a particular process would be subject to the affirmative procedure, in other words they could only be made if approved by both Houses of Parliament. Figures 3a and 3b illustrate our interpretation of how such a legislative structure may work.

Figure 3a: Proposed immediate situation: Legislation agreed which covers currently understood use of human-animal chimera or hybrid embryos for research, for example in the creation of cytoplasmic hybrid embryos.

Figure 3b: Proposed mechanism for revising legislation in consideration of developments in research.

101. We recognise that it will be necessary to define within the legislative framework the potential types of embryo and process to which it would apply. The definition would need to be wide enough to encompass all known and potential forms of animal-human hybrid, chimera and cytoplasmic hybrid embryos. We expect the Government to draw on the work of the Academy of Medical Sciences in this regard.

102. We recommend that the Government proposals in the draft Bill for the regulation of the creation of animal-human chimera and hybrid embryos be based on the legislative structures outlined in paragraph 100 of this Report.

Impact of the legislative structure on UK science

103. One consideration in establishing a legislative structure for research should be the impact which it may have on UK science. As we have seen earlier, the UK's regulatory system has traditionally been viewed as an important element in the pre-eminency of the UK in this scientific field. It has been viewed with envy by researchers from countries with more restrictive regimes and it has been influential in the development of policy-making in other countries.[237] There have to be concerns that changes to the regulatory system should not harm the reputation and make-up of the UK science base but should encourage it to develop in order to realise the expectations placed on it in terms of knowledge and tackling disease.

104. The current Government proposals have led some in both Government and industry to express concerns about their impact. The Department for Trade and Industry argued that the policy "may damage the widespread international view that the UK has one of the best regulatory systems in relation to stem cell research".[238] This is supported by the BioIndustry Association who told us that the Government's proposals to prohibit the creation of human-animal chimera and hybrid embryos for research "would halt current innovative research into diseases such as Alzheimer's and motor neurone disease" and that it would "send out an incredibly negative message about the UK as a location for stem cell research and innovative biomedical research". The Association argued that "the BIA does not believe that this is compatible with the Government's aim of ensuring the UK is a world leader in this field".[239] We believe that the term 'prohibition' used in the Government proposals can be taken to imply a negative approach to research in areas such as this, as opposed to the positive connotations implied through regulation of such research practice. A ban and the prospect of a ban in draft legislation on human-animal chimera or hybrid embryos would undermine the UK's leading position in stem cell research and the international reputation of science in the UK.

105. There are also issues in respect of the current competitive advantage UK scientists have in stem cell research. The DTI reported "strong views" from industry that a regulatory ban on the use of hybrids for research may harm the climate for both company and academic research".[240] One scientist, Professor Anne McLaren of the Wellcome Trust Gurdon Institute, commented that "no doubt this research would eventually be carried out in other countries, but at present UK scientists have a competitive advantage".[241] This was echoed by Professor Colin Blakemore of the MRC who believed that "the pace of progress in this field" is "really quite extraordinary". He thought that the UK had "an advantageous position in this through a relatively liberal approach but with a very firm regulatory environment" and that this put the UK in a strong position, "but with a lead which will very, very easily be lost, given the rate of progress".[242] He considered prohibitive legislation in this area to be "a serious disadvantage in a very competitive and exciting area of science.[243] When asked if it were possible to quantify the UK lead in this area, Mr David Macauley, Chief Executive of the Stem Cell Foundation claimed that "at the moment, the analogy is we are watching this like sand running though our fingers, our competitive advantage, and this proposed ban does nothing but accelerate that".[244]

106. One further possible negative impact on future competitiveness was raised with us by Professor Martin Bobrow, Deputy Chairman of the Wellcome Trust. He was concerned that "the long-term effect of creating an unpleasant public atmosphere needlessly around issues of this sort is that it discourages very able, young researchers from entering the field, and it can take a very long time to reverse that sort of trend, if it becomes established".[245]

107. We asked the Minister for her views on the suggestions that the UK may lose its competitive advantage in stem cell research in response to a ban on the creation of human-animal chimera or hybrid embryos for research, but were unable to obtain a clear response.[246] We are concerned that a ban or a proposed ban may not only encourage researchers to leave the UK in order to undertake their research in a more permissive regulatory regime, but it may also inhibit early stage researchers entering the field. Whilst we do not believe that UK competitiveness should dictate policy in a research area, we believe that the Government should consider this as a contributory factor and we recommend that the Government ensure that it is properly briefed on potential implications from future legislation in this area.

187 Q 91 Back

188 HC (2004-05) 7, recommendation 9, www.publications.parliament.uk/pa/cm200405/cmselect/cmsctech/7/7i.pdf Back

189 Department of Health, Review of the Human Fertilisation and Embryology Act: Proposals for revised legislation (including establishment of the Regulatory Authority for Tissue and Embryos), Cm 6989, December 2006, www.hfea.gov.uk/cps/rde/xbcr/SID-3F57D79B-9E450A32/hfea/White_Paper_Dec_06_web_version.pdf Back

190 Ibid Back

191 Q 295 Back

192 Q 125 Back

193 Department of Health, Review of the Human Fertilisation and Embryology Act: Proposals for revised legislation (including establishment of the Regulatory Authority for Tissue and Embryos), Cm 6989, December 2006, para 2.85 Back

194 Ev 152 Back

195 E.g. Ev 51, 64 Back

196 e.g. "Scientists fear ban on cloned embryo research", Financial Times, 5 January 2007 and "Nobel scientists urge fertility watchdog to back hybrid embryos", The Times, 10 January 2007 Back

197 Ev 131 Back

198 Q 5 Back