Let’s not move fast and break things: why caution is needed in our approach to heritable human genome editing (HHGE)

The possibility of South Africa being the first to allow heritable human genome editing is being presented by some legal scholars as global scientific policy leadership. But given existing safety concerns, the premature adoption of genome editing technologies like the CRISPR-Cas9 system for clinical applications will more likely lead to biomedical abuses and unintended harms due to the removal of reasonable legal and ethical safeguards.

Recent articles in Nature and The Conversation have suggested that South Africa may be the first country in the world to allow for heritable human genome editing (HHGE). This is a position championed by a group of legal scholars lead by Donrich Thaldar at the University of KwaZulu-Natal. Thaldar and his colleagues have published several papers in favour of South Africa allowing HHGE. They have recently argued that South Africa’s legislative framework makes HHGE permissible, especially in light of the third edition of the South  African  Ethics  in  Health  Research   Guidelines released in May of 2024. In a blog post, Jantina de Vries clarifies that most legal scholars in South Africa find this interpretation of the guidelines and the claim that the law allows HHGE to be unconvincing.  Even so, in a recent editorial in the South African Medical Journal, concerns have been raised about these guidelines that have led Ramsay and colleagues to call for the urgent revision of these guidelines.

Although the use of gene editing technologies for the purpose of HHGE is not legal at present, I agree with Thaldar and colleagues that there is merit to debating under what circumstances HHGE could or should become legal, and when its use could be ethically permissible. However, I disagree with these authors with what I argue to be their dismissive attitude towards the ethical questions that should govern whether HHGE should be adopted at this time. The superficiality of their engagement with the arguments of their critics and the ethical problems with these technologies are major areas of concern with their participation in this debate.

Central to these problems is that the case that Thaldar and his colleagues present in favour of HHGE depends on us taking the safety of gene editing technologies like CRISPR-Cas9 for granted. One of Thaldar and Bonginkosi Shozi’s papers ask “If the safety and efficacy issues relating to heritable genome editing can be resolved, how should liberal democratic societies regulate the use of this technology by prospective parents who wish to effect edits to the genomes of their prospective children?”—my emphasis on “if”. In another paper where they collaborated with other colleagues, they looked at whether the public agrees with policy positions that begin with the claim “Provided that it is safe and effective, our country’s laws should allow parents to choose to  use  genome  editing  before  a  child’s  birth”.

In this discussion, the presumed safety of HHGE and its associated technologies is not something that we can take for granted. This is especially true when one considers the demonstrable harms and unintended consequences that the use of the CRISPR-Cas9 system has led to in test subjects like rats and farm animals. Given that Thaldar and his colleagues go as far as to argue that this technology should be permissible for clinical interventions, it is worthwhile noting how such experiments have gone so far in test subjects before applying these methods to humans. Such concern about HHGE is not to discount the incredible strides that have been made in genetic therapies for diseases like spinal muscular atrophy; it is a caution against moving too fast and breaking things such as what happened in mice where gene editing reduced the incidence of cancer in the test subjects but also led to considerably lower life expectancy. The enduring safety and technical challenges faced by these technologies remain and are a heavily discussed topic in the scientific literature. Some of these problems are off-target effects and efficiencies in the delivery of gene edits among others.

These kinds of problems and the present inability to reasonably mitigate against serious unintended consequences has led to health professionals and particularly geneticists to call for a moratorium on heritable human genome editing. This call was made in the shadow of He Jiankui being jailed for leading the effort to produce the first two genetically modified children in China. This was widely seen as irresponsible and unethical scientific clinical practice. It is the present global consensus that before proposing any clinical applications to the use of gene editing technology like the CRISPR-Cas9 system in humans, we should make reasonable efforts to ensure that the technology is safe and that we are not putting children and all future generations at risk through an irresponsible and hubristic adoption of these technologies.

Against this global consensus, Thaldar and some of his colleagues have argued that criticisms of their favourable position for the adoption and use of HHGE in South Africa are “conservativism” and constitute ethical imperialism that impinges on the sovereignty of South Africa. This is a position he and other of his colleagues have repeated in the comments section of The Conversation. The accusation of cultural imperialism has served to silence some of their critics from abroad, but it does not deal with any of the substantive matters of ethical concern that have been raised about genetic editing in this context. The sovereignty of South Africa does not make irrelevant critiques about the risks we (South Africans and humans as a species) would face if we were to irreversibly alter the human genome in presently unpredictable ways—in ways whose safety and efficacy remains dubious. The special pleading of Thaldar and colleagues for us to overlook standard ethical concerns because of South Africa’s special cultural context and history risks exposing South Africans to exceptional harm by stripping South Africans of equal and ordinary ethical consideration. This position on the uniqueness of South Africans undermines hard-won bioethical norms in which all people, regardless of place or culture of origin, are to be given equal ethical regard and receive equitable protections in biomedical settings.

One of the strategies Thaldar and his colleagues are using to argue that the special cultural context of South Africa supposedly makes HHGE permissible and many of the ethical concerns critics are raising to be irrelevant is to rely on an expedient and liberal conception of Ubuntu. In their understanding of Ubuntu, and in their claim of a shared Ubuntu ethic in South Africa, they argue that the potential benefits of genomic editing for communities and their descendants make HHGE permissible within an Ubuntu framework. Anye Nyamnjoh argues that this kind of engagement with the philosophy of Ubuntu by Thaldar and his colleagues is “ethics washing”. This superficial engagement with the philosophy of Ubuntu in conjunction with the presumed safety of gene editing technology is the foundation upon which Thaldar and his colleagues build their case for HHGE. In this, they disregard all the various ways in which Ubuntu could lend support to the opposite conclusion they favour. If HHGE is not yet safe—a claim for which there is significant evidence to support—then what they say of Ubuntu does not follow. Moreover, if under Ubuntu we have the ethical obligation to be good ancestors by safeguarding the well-being of present and future generations, then it is all the more important for us to ensure we cause as little harm to our communities and our future descendants as we reasonably can. This would include avoiding the premature adoption of genomic editing technologies that could cause irreparable harm to present and future generations. These kinds of ethical worries are not taken seriously by Thaldar and his colleagues but they rather attempt to side-step these issues through employing their peculiar version of Ubuntu.

Another example that suggests that they do not take these ethical questions seriously is how they brush aside concerns about eugenics in respect to the use of HHGE in reproduction in South Africa. They claim that eugenics is a non-issue in South Africa and claim that worries about eugenics in relation to HHGE are only abstract ethical fears. This statement is false as eugenic practices are already a problem in the use of assisted reproductive technologies in South Africa and elsewhere. Reproductive assistive technology is one of Thaldar and colleagues’ main targets of use for HHGE, so it is both surprising and concerning that they would dismiss concerns about eugenics in relation to HHGE. Their views on eugenics ignore the long history of race-based eugenics in South Africa under colonialism and Apartheid, and the living legacies of eugenics that remain with us today in medical practice. It is advisable that they reconsider these challenges in respect to HHGE instead of denying that they exist.

Thaldar and his colleagues frame the possibility of South Africa being the first country in the world to legally allow heritable human genome editing as global scientific policy leadership. But the premature adoption of genome editing technology like the CRISPR-Cas9 system will more likely lead to biomedical abuses and unintended harms due to the removal of reasonable legal and ethical safeguards that are still available to people elsewhere. In respect to what policy positions we should take on HHGE, Thaldar and his colleagues should separate the hypothetical case where safety and efficacy issues relating to heritable genome editing have been resolved from the present-day reality where they have not been resolved and safety remains a central issue. This would help them stop to consider the strong arguments against HHGE and why its use is not permissible… at least, not yet.