Heritable Human Genome Editing [HHGE] – South Africa Law/Regulation/Ethics Guidance
We explore below the startling inclusion of HHGE as a “matter-of-fact” topic area in the 2024 South Africa Ethics in Health Research Guidelines. We certainly paused when we encountered reference to “the best interest of prospective children” [presumably resulting from HHGE] in 4.3.2 [c]: “…Ethical oversight should especially be illuminated by the right to freedom of scientific research, the right to access to healthcare, the best interests of prospective children, and the dignity of all individuals involved…”
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South African Ethics in Health Research Guidelines: Principles, Processes and Structures
2024 Third Edition
4.3.2 Heritable human genome editing
Research on heritable human genome editing (HHGE) holds significant potential for addressing genetic diseases and improving human health. It also presents ethical challenges that require careful consideration and deliberation. A framework for analysing the protocol emphasises responsible and cautious practices.
a) Scientific and medical justification
HHGE research must have a clear and compelling scientific and medical rationale, focusing on the prevention of serious genetic disorders and immunity against serious diseases. The potential benefits to individuals and society should outweigh the risks and uncertainties associated with HHGE.
b) Transparency and informed consent
Researchers must maintain transparency throughout the research process, ensuring that participants and stakeholders are well-informed about the goals, methods, and potential implications of HHGE. Informed consent must be obtained from all parties involved, including prospective parents and individuals whose genetic material is used in the research.
c) Stringent ethical oversight
HHGE research should be subject to rigorous ethical review by health research ethics committees to evaluate its ethical implications. Ethical oversight should especially be illuminated by the right to freedom of scientific research, the right to access to healthcare, the best interests of prospective children, and the dignity of all individuals involved.
d) Ongoing ethical evaluation and adaptation
Ethical scrutiny of HHGE research projects should be a continuous process that adapts to evolving circumstances. This entails regular re-evaluation as new information emerges and as the technology progresses.
e) Safety and efficacy
Researchers must prioritize safety in all HHGE experiments, with thorough assessments of potential risks and strategies for mitigating them. The research should demonstrate a high level of scientific rigor and provide evidence of the technique’s efficacy.
f) Long-term Monitoring
Researchers should commit to ongoing monitoring of individuals born as a result of HHGE interventions to assess their health, wellbeing, and potential unforeseen consequences.
g) Legal compliance
Researchers must adhere to all relevant laws governing HHGE research. In particular, researchers must adhere to the fourteen-day rule, and must obtain the necessary ministerial permission to conduct research on embryos.
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Credit to our colleagues Françoise Baylis and Katie Hanson for bringing attention to the underlying issues and raising questions about the current legal status of such research in their article in The Conservation [24 October 2024]. A number of commentaries and articles ensued including Sarah Wild’s piece in Nature [07 Nov 2024]: Will South Africa become first country to accept controversial form of human genome editing?
ARM’s Executive Director Tim Hunt weighed in as well on LinkedIn [at least] noting:
…This misguided type of ‘research’ must not overshadow the tremendous progress being made every day by leading biotechnology companies and academic pioneers in the field of somatic cell gene editing and gene therapy. There must be a bright line between that kind of important, well-regulated, and ethical R&D that is in service to patients living with life-threatening rare disorders vs. the highly speculative and troubling world of HHGE. This development highlights the need for continued convening – with leading biotechnology companies, scientists, medical experts, patients/patient groups, bioethicists, religious leaders, regulators, and legal scholars – around the topic of HHGE.
The latest on all this appears to be a round-up article by Pete Shanks in Biopolitical Times: South Africa Does Not Allow Heritable Human Genome Editing [11.24.2024] as carried on the Center for Generic and Society website.
A number of commentaries have referenced a statement on November 8, 2024 by Professor Penelope Engel-Hills, Chairperson of the National Health Research Ethics Council , responding to The Conversation piece by Baylis and Hanson referenced above. Here is an excerpt [our text bolding]:
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…Firstly, the National Health Research Ethics Council of South Africa (NHREC) wishes to clarify that neither the National Health Act, nor the 2024 National Guidelines on Ethics in Health Research, legalise HHGE for use in therapy in any way. The prohibition in the National Health Act makes this position very clear. The “reproductive cloning of a human being” is prohibited in section 57(1) of the National Health Act, punishable as a criminal office by a fine and up to 5 years’ imprisonment. Furthermore, the same section states that the Minister may permit research on stem cells and human fertilised eggs that are less than 14 days old. We believe that “reading in” a permissive approach concerning HHGE to the guidelines is unconvincing but, nevertheless, we will address this potential confusion by clarifying the wording in the 2024 ethical guidelines.
The NHREC concedes that the wording in the guidelines may have caused some confusion and unnecessary alarm. However, it is important to note that the 2024 research ethics guidelines are grounded in a set of key principles that ensure the integrity and ethical conduct of research involving human participants. As a principle-based document, the context of the entire set of guidelines is relevant and we caution against any interpretation that fails to consider the key principles expressed in the guidelines. These ethical guidelines provide a framework for ethical reasoning and decision-making rather than a set of legal rules.
As the prohibition of HHGE is stated in the National Health Act, the 2024 research ethics guidelines stipulate with regard to HHGE that South African researchers “must adhere to all relevant laws governing HHGE research” (par 4.3.2(g)). Section 73 of the National Health Act requires every organisation that conducts “health research” to have a health research ethics committee (registered with the NHREC) or have access to a registered health research ethics committee that must review research proposals and protocols, and grant approval where research proposals and protocols meet the prescribed ethical standards; and have oversight on the approved study. The definition of “health research” is broad, meaning that HHGE research would fall within the scope of health research, making ethics approval a legal requirement…
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At this writing, [14 December 2024] we find no posted statements or comment on the relevant SA Department of Health website pages around this, so we are left, for the moment, with the not-entirely-satisfying construction in Professor Engel-Hills’ statement text above.
Two additional analyses have been published over the last week.
One is titled South Africa’s new research guidelines are not a green light for heritable human genome editing [The Conversation, December 4, 2024] by Bonginkosi Shozi. This piece explores the relevant South Africa statutory provision Section 57(1) of the South African National Health Act, the role of the national ethics guidance at issue above, and the independent role that ethics review bodies presumably enjoy in reviewing protocols that involve HHGE, utilizing that national ethics guidance. This analysis does not seem to move things forward.
The other is an editorial titled Heritable human genome editing in South Africa – time for a reality check [South Africa Medical Journal, Early Online -2024-11-29] by Michele Ramsay, Michael Pepper, Jantina de Vries, Safia Mahomed and Eleni Flack-Davison. The editorial is well structured and provides discussion of the “origins of the current controversy” and its consequences. One contextual clarification in the piece is around public consultation processes leading to the inclusion of the HHGE language in SA guideline referenced above:
“…A draft of the guidelines released for public comment in 2023 did not include text on HHGE. A subsequent draft released early in 2024 included the section on HHGE with a brief window for comment. It is unclear why the National Health Research Ethics Council (NHREC) chose not to consult widely with topic experts to ensure that the text of the guidelines was appropriate, considering the national legal context, ethical concerns and international recommendations and guidelines for HHGE. It is unfortunate that this situation has arisen. The misguided wording in the current guidelines may serve to precipitate a troubling change in opinions in favour of permitting or promoting HHGE in SA…”
More important is the editorial’s clear-thinking conclusion:
…What should happen next?
Revision of the NHREC guidelines
The NHREC must clarify its view on HHGE. We note the recent press release that was circulated to ethics committees around the country by the chair of the NHREC on 8 November 2024. But this does not sufficiently address nor resolve the controversy, and the press release has no legal standing. The current wording for HHGE for research purposes in the guidelines should be deleted in its entirety. The underlying premise of section 4.3.2 of the guidelines appears to rest on the fact that there will be prospective parents, prospective children and individuals born because of HHGE research interventions specifically, which is problematic and inconsistent with the law. In addition, this current ambiguity in wording blurs the line between HHGE research and clinical application
So…all this suggests an extremely important, troubling and still unresolved matter with global implications. We will continue to monitor for any further analysis, and, hopefully, action!
Center for Genomic Medicine Governance, Ethics & Policy 