The Human Fertilisation and Embryology Act was enacted in 1990 and revised in 2008 in response to two types of change: social and technological. But how responsive is it to the pace of change? In contemplating revision of the Act, how might we optimise its responsiveness to clinical need while upholding standards?
In the years between 1990 and 2008, as new attitudes to gender and parenthood emerged, so did new understanding and evaluation of the subject matter of human reproduction. Within six years of its enactment, the Act's core definition, 'embryo', had been challenged by a sheep (see BioNews 1131). Within 32 years, our understanding and ethical appraisal of embryos have been enriched by studies of their development and genomic activity. The idea of genomics, entirely absent from the mind-set of the 1990 Act, is now embedded in public thinking. So, too, is the idea of genomic intervention. Not only has the possibility of using genetic technology to relieve and prevent human suffering significantly advanced, but the rate of advance has accelerated. Clinical possibility is outpacing regulatory response.
With hindsight, this is apparent in the 2008 revision of the Act, when Parliament sanctioned the purpose of preventing 'the transmission of serious mitochondrial disease'. It was prompted by a technique for fulfilling that purpose, mitochondrial donation, which was expected to be clinic-ready within a few years. The revised Act empowered government to pass regulations to permit clinic-ready 'prescribed processes'. Seven years later, two 'prescribed processes' for preventing 'the transmission of serious mitochondrial disease' were approved. Yet, even as debate raged about 'three-person IVF, a discovery had been made that could, in principle, obviate the controversy altogether because no donor eggs would be needed: the faulty mitochondrial DNA in the mother's own egg could be corrected using a new genetic technology: CRISPR.
It's questionable whether CRISPR would actually work better than the two 'prescribed processes', but the possibility illustrates how new technologies are restricted even though their purpose is accepted at the highest level. If we wanted to add a CRISPR 'prescribed process' to the other two, it would be necessary for both Houses of Parliament to approve it: the Act prescribes that viscounts, bishops and lay MPs are required to approve technology for a use that is already lawful.
This is extraordinary. Contrast the approval of technology for preventing 'the transmission of serious mitochondrial disease' with the approval of a new diagnostic kit: Parliament does not quiz the results of performance evaluations; nor does the use of the kit require political permission. Thankfully, safety and utility are assessed according to prescribed standards by an independent, expert assessment body which confirms compliance on the basis of a non-political assessment. In both cases, Parliament has approved the purpose, but in the case of diagnostic tests, assessment is delegated to independent expert bodies; an arrangement that protects consumers while enabling innovation.
Parliament does not approve any other clinical genome editing approach. Rather, the Medicines and Healthcare products Regulatory Agency turns to criteria such as those of the European Medicines Agency guideline on quality, non-clinical and clinical aspects of medicinal products containing genetically modified cells. It's therefore not obvious why the assessment of heritable intervention technologies (of all things) should require non-expert approval.
Parliament long ago accepted that, provided the purpose is 'to prevent the transmission of serious mitochondrial disease' to a person developed from an embryo in which the mitochondrial or nuclear DNA has been altered (or to which a cell not arising from its development has been added) it will be lawful to implant it under a licence. In amending the Act, shouldn't technical and clinical matters be disentangled from statutory purpose? Shouldn't technologies for preventing 'the transmission of serious mitochondrial disease' be approved by a Clinical Technology Review Body (CTRB), rather than by Parliament?
a) participate in the International Scientific Advisory Panel (ISAP) recommended by the 2020 International Commission report (among other assemblies, including those proposed by the WHO Committee);
b) participate in the development of international standards for heritable interventions;
c) engage closely with regulators of non-heritable clinical editing technologies in other jurisdictions;
d) develop and update national technical and clinical requirements;
e) authorise clinic-ready technologies and their heritable serious disease targets nationally; and
f) be open, transparent and accountable (in line with the WHO Committee's recommendation).
Neither the HFEA's Statutory Approvals Committee (SAC), nor its Scientific and Clinical Advances Advisory Committee (SCAAC) fit the bill: SAC does not assess technology, while SCAAC has too broad a remit and lacks the power to approve new technologies. Each is poorly resourced and neither is independent of the licensing authority of which they form part. They are, nevertheless, commendably small: the specialist Committee for Advanced Therapies might appear a good model, but it would be vastly out of proportion to requirements, not least because no 'product' is to be marketed.
It would be ironic if, in freeing technology assessment from politics, the CTRB became a bureaucratic obstacle to adaptive regulation. On the contrary, it must be fleet of foot, responsive to the needs of clinicians and researchers, and prepared, with transparent justification, to approve technologies in advance of ISAP or related standards. Get it right, however, and the UK might not only set another international example in the field of embryology regulation, but effectively kick-start the ISAP. Given its role in the International Commission, perhaps the Royal Society could take the initiative here?
A CTRB would be concerned with technical processes, but human embryos are not products. Each is a potential person, the welfare of whom arises during early development and is the responsibility not of manufacturers, but of clinicians. It therefore seems wise to keep the establishment of standards and the oversight of heritable intervention technologies distinct from clinical licensing. The fact that a technology meets a requisite standard is manifestly not the same as permission to use it, a distinction reflected in the Act's approach to mitochondrial interventions: not only the process must be 'prescribed', but so must the circumstances of hereditary and pathological risk.
It falls to SAC to determine whether these circumstances arise in an application for a mitochondrial intervention licence. In principle, it could remain as adjudicator of 'prescribed circumstances' on a genome editing brief, on the basis that these circumstances provide the trigger event for licensing approval. However, by the HFEA's own admission, SAC lacks appropriate expertise. Nor is it conspicuous for its transparency. As clinical applications would be considered on a case-by-case basis, it's arguable that approval by a specialist, transparent research ethics authority would command as much public trust as a licence.
Unlike mitochondrial donation, there are many more than two potential processes for preventing the transmission of harmful gene variants. This makes the need for a CTRB inescapable, but only if Parliament answers the key social question. Given that it already permits nuclear DNA editing for the purpose of preventing 'the transmission of serious mitochondrial disease' and given the wider potential of genome editing approaches, can Parliament justify restricting access to hereditable interventions to the prevention of only mitochondrial diseases?
In legislative terms, the question becomes whether the existing statutory purpose should be widened to (something like), 'to prevent the heritable transmission of serious disease to a person developed from that embryo'? This is not a scientific question. However, to be 'properly considered' as the WHO Statement on governance and oversight of human genome editing recommends, the question not only requires legislative honesty, but the first class scientific briefing of Parliamentarians.