Scientists call for public debate on altering DNA to prevent diseases
On 2nd September, a group of leading UK research funders issued a statement calling for an urgent national debate on the ethics of genetically modifying human embryos and other tissues to prevent serious diseases. The group, comprising the Wellcome Trust, the Medical Research Council, the Academy of Medical Sciences, the Association of Medical Research Charities and the Biotechnology and Biological Sciences Research Council:
- supports the continued use of CRISPR-Cas9 and other genome-editing techniques in preclinical research, which includes the use of the technology for research purposes in human reproductive cells and early embryos, where this is fully justified, scientifically and ethically, and within the confines of the law;
- states that it will continue to fund and support research of this kind, as well as studies that further progress and refine these technologies; and
- calls for widespread discussion among scientists, ethicists and the wider public about how these emerging techniques may in future be applied clinically, in human reproductive cells and early embryos, to treat or prevent serious genetic disease.
The science of genome editing is summarized on the Wellcome Trust site, here. The joint statement explains:
“Genome editing is a powerful research tool that allows sections of DNA in the genome to be precisely removed or replaced using ‘molecular scissors’. The concept of genome editing is not new, but rapid developments in the technology – namely the emergence of the CRISPR-Cas9 system – mean that targeted, highly efficient editing of DNA in cells has become relatively simple.
Our understanding of CRISPR-Cas9 is still at an early stage, and any potential treatments based on this technique are many years away. The first clinical applications of CRISPR-Cas9 are likely to involve editing the DNA in somatic (non-reproductive) cells – for example, by removing them from a patient and editing them in a lab to correct a harmful mutation before putting them back into the body. There is already some work in progress to do just this in diseases including HIV, sickle-cell disease and haemophilia, and emerging potential for cancer therapy.”
The editing of human germ cells or embryos falls within the ambit of the Human Fertilisation and Embryology Act 1990, as amended, and is regulated by the Human Fertilisation and Embryology Authority (HFEA), the UK’s independent regulator of treatment using eggs and sperm and of treatment and research involving human embryos. Under the Act, research can only be undertaken on embryos of up to 14 days of age and under the authority of a specific HFEA licence. Under the current provisions, genome editing could only be undertaken in a research context and the use of such material in humans or for treating patients is expressly prohibited.
The editing of somatic cells, (i.e. any cell of the body except sperm and egg cells) is regulated by the Human Tissue Authority (HTA), established under the Human Tissue Act 2004; the HTA regulates matters relating to human bodies, organs and tissue for research and transplantation. As an Advanced Therapy Medicinal Product (ATMP), the clinical application of somatic cell therapies would be regulated by the HTA and licensed by the Medicines and Healthcare products Regulatory Agency.
The Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015 became law earlier this year; no new primary legislation was required as the 1990 Act empowers the Secretary of State to make regulations under the affirmative resolution procedure. Following the Commons vote of 382 to 128 in favour, [3 Feb 2015 Col 160], the House of Lords approved the SI following the rejection of Lord Deben’s amendment by 280 to 48 [24 Feb 2015 Col 1569]. We reported on the House of Lords debate here.
In its response to the consultation on this technique, the Government indicated that it had adopted the working definition that “genetic modification involves the germ-line modification of nuclear DNA (in the chromosomes) that can be passed on to future generations”. On this basis, the view of Government and of the HFEA was that that the proposed mitochondrial donation techniques (as in the 2015 Regulations) would not constitute genetic modification”, [Commons Hansard Feb 2015 Col 186]. The Government argued that, on that basis, the technique could be accommodated within both UK and EU legislation.
During the debates on mitochondrial donation the applicability of the EU Clinical Trials Directive, Directive 2001/20/EC and the Clinical Trials Regulation (CTR) EU No 536/2014, (which will be effective after 28 May 2016) was discussed. Both include the provision that “[n]o gene therapy trials may be carried out which result in modifications to the subject’s germ line genetic identity”: Articles 9 and 90, respectively. In the Commons debate, the Parliamentary Under-Secretary of State for Health, Jane Ellison, asserted:
“[t]he clinical trials directive applies only to medicines. It does not apply to embryology, so it is not relevant in this case”, [3 Feb 2015 Col 163].
“[t]he clinical trials directive is … part of a suite of EU measures that set out common rules across Europe to ensure the free movement of safe medicines in the EU. Mitochondrial donation is not a medicine, so those provisions do not apply. The follow-up assessment of the treatment’s efficacy is part of good clinical practice”, [3 Feb 2015 Col 186].
In the Upper House, Lord Mackay of Clashfern (Con) gave his analysis of the legality of the draft UK Regulation, [24 Feb 2015 Col 1600] as follows:
“So far as I have understood the European treaties, they do not confer an authority as yet to interfere in the medical procedures within the member states. That is basic, and means that they cannot interfere or render unlawful a medical procedure such as the one proposed in these Regulations … no challenge, so far as I know, has been offered by the European Commission to the provisions in the 2008 Act—which of course would be the right place to challenge this, if it were unlawful …”
On the basis that mitochondrial donation techniques do not constitute genetic modification, these exchanges in the Lords and Commons were not relevant. However, these issues will need to be revisited in relation to genome editing both of human germ cells or embryos and of somatic cells. With regard to the latter, the funders’ statement acknowledges that somatic cells are regarded as an Advanced Therapy Medicinal Product, (ATMP), i.e. they fall within the definition of “medicinal products” within the meaning of Annex I to Directive 2001/83/EC of 6 November 2001, as amended by Regulation 1394/2007 of 13 November 2007. By extension, they fall within the ambit of the EU clinical trials provisions.
To date, framework primary legislation in UK has been in place in anticipation of scientific developments in this area: the preamble to the Human Fertilisation and Embryology Act of 1990 states inter alia: it is “[a]n Act to make provision in connection with human embryos and any subsequent development of such embryos”; and the introduction of a new section 35A via the 2008 Act empowered ministers to introduce legislation relating to mitochondrial donation which has only this year been introduced through the Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015.
Part 1 of the 2008 Act takes account of scientific developments to reflect changes in social attitudes and updates the regulatory provisions relating to the HFEA; Part 2 introduces a new concept of “parenthood” for a mother’s female partner in certain circumstances, making equivalent provision to that for opposite-sex couples. Part 3, inter alia, amends the Surrogacy Arrangements Act 1985.
With regard to the recent joint statement on genome editing by the consortium led by the Wellcome Trust, existing legislation permits the present use of gene editing for non-clinical research purposes in germ cells, including human embryos up to 14 days old. However, the joint statement calls for “this type of research to be allowed to continue and … a broad and inclusive discussion about genome editing and its future implications”. With regard to the continuation of the current type of research,
“[o]ur understanding of CRISPR-Cas9 is still at an early stage, and any potential treatments based on this technique are many years away. The first clinical applications of CRISPR-Cas9 are likely to involve editing the DNA in somatic (non-reproductive) cells – for example, by removing them from a patient and editing them in a lab to correct a harmful mutation before putting them back into the body. There is already some work in progress to do just this in diseases including HIV, sickle-cell disease and haemophilia, and emerging potential for cancer therapy”.
In terms of future applications, it states:
“[t]here has also been some suggestion that genome editing could be used clinically in the future to edit the DNA of human eggs and sperm, or early embryos (known as germline editing). The difference here is that any changes made would be passed on to future generations. This is prohibited under UK law and is unlikely to be allowed in any European jurisdiction at present”.
As in the case of the Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015, no new primary legislation would be required in the UK; the 1990 and 2004 Acts empower the Secretary of State to make regulations under the affirmative resolution procedure. However, in view of the difference between genome editing and mitochondrial donation, such techniques are likely to attract much greater opposition.