Aligning research legislation: interspecies embryos and animals containing human material

In 2008, important changes were made to the legislation governing the use of human embryos in research, the UK Human Fertilisation and Embryology Act (HFE Act) 1990. The legislation was extended to five categories of 'human admixed embryos' containing human and animal cellular or genetic components, which were brought within the licensing regime of the HFE Act, including the regulatory purview of the Human Fertilisation and Embryology Authority (HFEA). This meant that human admixed embryos could be used in vitro for up to 14 days (or until the appearance of the primitive streak) for specific types of medical research but only with the approval of the HFEA, and in line with the other requirements of the HFE Act.

In defining these conditions, Parliament set a contemporary regulatory and ethical framework for research involving predominantly human embryos and human/animal hybrid embryos. However, the legislation did not address 'embryos at the animal end of the spectrum' and other animals containing human cellular or genetic material.

In contrast to research involving human admixed embryos, experiments involving the integration of human DNA, cells or tissues into animals have been undertaken since the 1960s. Transgenic animals (containing one or more human genes) or chimeras (with some human cells or tissues amongst their own animal tissues) are an important biomedical research approach. They can be referred to collectively as 'animals containing human material' (ACHM). Animal research conducted in the UK, including ACHM research, is regulated by the Home Office through a robust system of licensing and inspection defined under the Animals (Scientific Procedures) Act 1986 (ASPA).

ACHM are used in many fields of biomedicine to understand human bodily function or disease where it is morally or practically impossible to conduct the experiments in humans, and where alternative approaches, such as computer simulations or cell cultures, are insufficient. Some ACHM are used to determine the function of human genes. Others are used to develop or produce therapies. In reproductive research for example, small pieces of human fetal testicular tissue can be implanted into immune-deficient mice where the tissue's normal growth continues. The transplants provide a way of studying human germ cell development dynamically in vivo and are used to study the origins of disorders such as testicular cancers, as well as to inform the development of fertility treatments and contraceptives. Similar approaches are used to model the female reproductive system, using transplanted human endometrial samples to investigate normal endometrial physiology and its malfunction in disorders including endometriosis.

The use of ACHM for research in the UK since the 1960s has not provoked major ethical questions or regulatory challenges. However, research technologies are advancing rapidly. More extensive manipulation of DNA is becoming possible and methods involving the substitution of animal's tissues with human stem cells or even entire organs with human-derived equivalents are now being envisaged. The Academy of Medical Sciences' 'Interspecies Embryos'  report of 2007 (1) indicated that the increasing power and sophistication of such techniques are likely to present significant challenges — both regulatory and ethical — in the foreseeable future.

To take forward this discussion and inform future governance of ACHM, the Academy of Medical Sciences drew together a working group, chaired by Professor Martin Bobrow CBE FRS FMedSci, in late 2009. The group's aim was to consider the research use of ACHM from scientific, ethical, social and safety perspectives, and to make recommendations for its future regulation.

Over 18 months, we sought and reviewed evidence from an open consultation, experts, and published literature. We commissioned a public dialogue ('Exploring the boundaries' (2))  to seek to understand the specific concerns of the UK public around ACHM. We addressed difficult questions, such as the extent to which it would be acceptable to substitute human cells in the brains of rodents or primates to study therapies for brain repair in conditions such as stroke. We also considered where the line should be drawn to best fulfil ethical, social and scientific interests, and how effective regulation might be achieved.

Our report, 'Animals containing human material' (3), was published in July 2011. In that report we identified three areas of potential future research that we concluded would require careful consideration and oversight in the future:

• the substitution of an animal's brain cells with human cells, to a degree which might lead to human-like cognitive capacity in the animal;

• research involving human—derived reproductive cells especially where there is a possibility of fertilisation in an animal; and

• the creation of animals which in some way resemble humans in their outward appearance or characteristics.

We recommended that the Home Office put in place a national advisory body with a duty to advise on the use of ACHM in research including on experiments falling into the above categories. We also concluded that a small number of experiments (including for example, the development of human-derived germ cells in an animal where this might lead to embryo production), should not be undertaken for the moment, at least until there is greater understanding of their likely outcomes.

In September 2010 a new European Directive on the protection of animals used for experimental purposes came into force. The Directive must be transposed into UK legislation by January 2013. The transposition process provides an important opportunity to update the UK's animal research legislation to take into account (potential) scientific developments. We hope that a national expert body with a remit to provide advice on ACHM is established as part of that process.

In the course of developing our report, it became evident that the regulatory framework for research involving ACHM is complex. Notably, it involves several regulatory agencies and Government departments, as well as numerous pieces of legislation. Close alignment of the work of these regulators will be essential in securing comprehensive and functionally efficient governance of ACHM research. We therefore recommended that the Department of Health and the Home Office (and their respective regulatory bodies and advisers) work closely together to ensure there are no regulatory gaps, overlaps, or inconsistencies between their respective regulatory systems.

Whilst we focused on UK regulation, we noted that ACHM research, like biomedical research more generally, is an international activity. We observed that little, if any, international guidance relating to research involving ACHM has been developed to date. Thus, our final recommendation focussed on the importance of raising awareness and promoting consistency in research practice at an international level, including through the development of international standards and guidance for researchers.