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Differentiating between human and non-human interspecies embryos
  1. Calum MacKellar
  1. Correspondence to Calum MacKellar, Scottish Council on Human Bioethics, 15 Morningside Road, Edinburgh EH10 4DP, UK; Calum.MacKellar{at}schb.org.uk

Abstract

Following the debate in the UK House of Lords, in December 2012, uncertainty remains as to the manner in which human and non-human interspecies embryos are differentiated in law.

  • Animal Experimentation
  • Bills, Laws and Cases
  • Embryos and Fetuses
  • Chimeras
  • Moral Status

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Should certain human–non-human interspecies embryos come under human or animal legislation? This was a question that was discussed in the UK House of Lords, in December 2012, whereby grave ethical concerns were expressed due to the sensitivity of the general public towards the moral status of embryos considered to be human. It took place in the context of the new Animals (Scientific Procedures) Act 1986 (ASP Act 1986) Amendment Regulations 2012 transposing the European Directive 2010/63/EU on the protection of animals used for scientific purposes which had to be implemented on 1 January 2013.

The debate occurred because some human–non-human interspecies embryos, and especially chimaeras formed of both early human and non-human cells, are difficult to categorise in legislation.

In the UK, the Human Fertilisation and Embryology Act 2008 (HFE Act 2008) regulates through the Human Fertilisation and Embryology Authority (HFEA)i human admixed embryos which are embryos at the human end of the spectrum. These include (in a catch-all category) any embryo containing nuclear or mitochondrial DNA of a human and nuclear or mitochondrial DNA of an animal but in which the animal DNA is not predominant.1 All other kinds of human–non-human interspecies embryos would then either be unregulated or fall under the more permissive ASP Act 1986.

Deciding, however, how to categorise some interspecies embryos is no simple matter. It challenged the final House of Lords discussions relating to the HFE Act 2008 whereby the Government Health Minister, Lord Darzi of Denham, gave some further explanations indicating that: If it were considered that an embryo was to be created in which the human DNA would ultimately predominate, an application for an admixed research licence would have to be made to the HFEA at the outset. This is because a licence is required to bring about the creation of a human admixed embryo. If a researcher was intending to create an embryo that would at some stage be predominantly human, for however short that time might be, they would need a licence to do so.2

This means that the word ‘predominant’ covers the whole period of an entity's possible existence. In other words, any chimaeric embryos in which the animal cells first predominate but where the human cells eventually develop into a majority—for however brief a time—would be covered by the catch-all category of the HFE Act 2008. This creates a difficulty, however, since in research it may be impossible to know in advance whether a chimaeric embryo in which the non-human cells first predominate might eventually become an embryo in which the human cells predominate.

Lord Darzi also indicated on the same day that human admixed embryos include those embryos in which human ‘functionality’ may predominate stating that: In the case of an embryo in which the brain might be predominantly animal, it is worth reminding ourselves what we mean by ‘predominant’. We refer not only to the percentage of the DNA but also to its location and functionality. If that entity had a human brain, that could clearly have a predominant function so, by definition, it would be at the human end of the spectrum of human admixed embryos and would require an HFEA licence.3

In this respect, and in a reply to a question in the House of Lords asking whether this meant that even though the human cells of an interspecies embryo ended up being a minority in the brain of a non-human animal, they could still be considered to predominate in certain circumstances, Lord Darzi replied: [T]he answer is yes. If that functionality predominates being human, that embryo will be classified as being at the human end of the spectrum of human admixed embryos.4

However, this then raises the question about the definition of functionality, to which the UK House of Commons minister of health responded: The point that Lord Darzi was making is that it is not necessarily the amount of DNA that would determine predominance, but what the DNA actually does … Each case would have to be considered separately. It will be for the Human Fertilisation and Embryology Authority to apply the test in practice, and ultimately for the courts to determine in law what this test should be in any particular case.5

This means that the term ‘human functionality’ will probably remain ambiguous and it is far from clear how researchers will be able to determine, with any certainty, which legislation to follow. The same problem was raised by the non-governmental Academy of Medical Sciences' 2011 report entitled Animals Containing Human Material which indicated that ‘the UK legislative structure is such that some awkward cases may fall at the boundary of jurisdiction’,6 adding: It is a matter of expert judgement to distinguish between embryos that are ‘predominantly human’ and so come under the HFE Act [2008], and embryos that are considered to be narrowly on the other side of the boundary and so ‘predominantly animal’, and outwith the terms of the HFE Act [2008].7

This difficulty in categorising certain human–non-human interspecies embryos was what challenged the Government Minister responsible for animal research, Lord Taylor of Holbeach, in December 2012. He admitted that this area was ‘extremely complicated’8 emphasising, however, that ‘If anything occurs outside the scope of HFEA, it must be considered by the Animals in Science Committee’ created under the new regulations, adding ‘Approval will be given only following careful consideration and in consultation with HFEA’.9 He also confirmed that the new Animals in Science Committee would have an ethical remit and would not permit contentious projects without very serious and careful consideration.9

In his presentation to the House of Lords, Lord Taylor was reflecting the conclusions of the Academy of Medical Sciences’ report, which indicated that it would be necessary for UK scientists to either10

  • hold licences for the research under both human legislation and non-human legislation from the outset of the experiment, or

  • ensure, through close monitoring, that the experiment was immediately halted if the outcome was unexpected and the experiment was being conducted solely under non-human legislation and it became evident that the human threshold had been reached. Further authorisation from the body regulating human legislation should then be sought before resuming the research.

An example of the kind of research where such concerns become relevant is revealed in the international patent application, lodged in 2000, for the production of human cells, tissues and organs using human–non-human chimaeric animals for transplantation into patients.11

In order to provide further guidance in this area, the Animal Procedures Committee, which was abolished in the new ASP Act 1986 Amendment Regulations, published a short report, in November 2012, which indicated that the Ministry responsible for animal research, HFEA and the Ministry of Health in the UK had all accepted the recommendations (which have no legal weight) presented at the end of the Academy of Medical Sciences' report.12 These proposed a number of categories in which experiments involving animals containing human material could be classified,13 namely:

  1. The great majority of experiments in which animals containing human material do not present issues beyond those of the general use of animals in research. These should be subject to the same oversight and regulation under ASP Act 1986 as other animal research.

  2. The limited number of experiments with animals containing human material which should be permissible subject to additional specialist scrutiny on a case-by-case basis by an expert body. Strong scientific justification should be provided to this expert body, which should closely consider the ethical and safety issues in addition to the potential value of the research.

  3. The very small number of experiments which should not be possible, at present, because they lack compelling scientific justification or raise very strong ethical concerns.

The UK government should be commended for seeking to address all human–non-human embryonic entities of uncertain status. However, because the new ASAP Act 1986 Amendment Regulations 2012 only address live animals who are born or who will develop past the last third of their normal gestation, and not embryos or fetuses as such, some areas remain problematic.

For example, this would happen when the research sourced biological material, without performing any regulated procedure to a living protected animal such as the use of post-mortem material removed from humanely killed animals. Eggs could be obtained from animals in an abattoir and fertilised by non-human sperm of the same species to provide a large number of early embryos without being regulated, in any way, under the ASP Act 1986. Human pluripotent stem cells could then be added to these embryos without researchers ever being certain whether these chimaeric embryos should come under the HFE Act 2008. This is because the scientists would not know whether the chimaeric embryos are able to reach a stage in which the human DNA would ultimately predominate or have a human ‘functionality’ if they are not left to develop for whatever reason.14

However, these embryos may still be considered as having a moral value (or given the benefit of the doubt) by a large section of UK society, since it is possible that they may reach an ethically sensitive stage but are not left to develop.

In summary, it may be necessary for the UK Parliament to provide additional regulatory provisions relating to certain human–non-human interspecies embryos after extensive and appropriate public discussion.ii These could then make sure that there are no regulatory gaps, overlaps or inconsistencies between human and non-human regulations in order to avoid any risks that contentious experiments may evade appropriate scrutiny.6

References

Footnotes

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • i Or any successor body.

  • ii This, unfortunately, could not be envisaged in December 2012 since the European Communities Act 1972 only enables regulations to enact the provisions of the Directive 2010/63/EU which did not address human–non-human interspecies entities.