Human gene editing involves targeted modification of the human genome. His potential applications, particularly therapeutic, are numerous. But while several achievements already exist, scientific, medical and ethical discussions are going well.
Thus, a world congress on gene editing took place in London at the beginning of March, and the first gene therapy based on targeted modifications of the genome could be validated this year by the Food and Drug Administration American. This therapy targets sickle cell disease, a “rare” genetic blood disorder that affects millions of people around the world. Where previous therapies have had little success, the new therapy may prove more effective.
Gene editing raises many issues, reminiscent of the discussions on recombinant DNA at the Asilomar conference in 1975, or those on cloning following the birth of Dolly the sheep in 1996. Let us focus on three of these issues that are particularly salient in current discussions: the question of the heritability of modifications to the human genome, that of regulation, and that of equity in access to gene therapies.
Can we edit the genome of our descendants?
Two fields must be distinguished in human genome editing. On the one hand, there is research on “somatic” cells, cells that are not hereditary. On the other, there is research on germ cells, which carry the information that is passed on to the next generation. Research on these "hereditary" cells raises other types of questions, often more complex, because they will have effects on an individual's descendants.
Indeed, with regard to the editing of the hereditary human genome, the safety and effectiveness of the techniques have not yet been demonstrated, a societal debate is lacking, as is responsible governance on the subject. The scientific community currently believes that conditions are not met to edit hereditary cells.
Genome editing of somatic cells, on the other hand, poses fewer ethical, political and technical problems and its future looks brighter. Thus, scientists explore different topics, such as heart and muscle diseases, engineering of donor cells to prevent rejection by a host's immune system, diseases such ashemophilia B, mucopolysaccharidosis or Beta-thalassemia. In all, several hundred patients are involved in experimental protocols. Gene editing has the potential to cure previously incurable diseases.
Added to this enthusiasm for applications is an enthusiasm for the technology itself. It was in 2012 that CRISPR-Cas9, the most famous gene editing technique, began to be used. Since then, its efficiency and accuracy have been continuously improved.
In addition, other techniques are now used, such as basic editing or prime-editing, which promise even more precision. Scientists hope to eventually be able to avoid so-called effects off-target (i.e. outside the targeted gene). But also those, less known, which pose problems on the target (effects on target) and show that the effects of CRISPR-Cas9 are “more chaotic than expected”.
“CRISPR babies”: a still hot controversy and a regulation that remains fragile
Despite this enthusiasm, it is difficult to forget the major troublemaker in the field of genome editing: He Jiankui. His announcement, via videos posted on YouTube at the end of November 2018, of the birth of two twin girls whose genome he had modified in the embryonic state by genome editing, had sent shock waves within and beyond the scientific community. “Irresponsible”, “illegal”, “unethical”: the condemnation of the scientific community of the experimentation was unanimous and immediate. By labeling He's experiment as such, this work of demarcation – one can even speak of excommunication – was a means for the scientific community to reaffirm and protect its moral authority, and to reassure the scientific community, as well as the public.
Five years later, the controversy caused by He Jiankui is not extinguished. At Third International Summit on Human Genome Editing, which was held in London from March 6 to 8, 2023, the scientists recalled this work, evoking a "dramatic" event and recalling how the announcement of He Jiankui "dominated" the discussions in 2018 (Robin Lovell-Badge, organizer of the summit Londoner). David Baltimore, Nobel Prize, co-organizer of the first two summits, underlined that probably "international regulation had failed", while reassuring that it was about a "singular event which has never happened again" ( note, however, that Denis Rebrikov had announced his intention to edit human embryos in 2019 and that research on surplus human embryos from in vitro fertilization clinics is ongoing).
An entire session of the summit in London was therefore dedicated to the issue of regulation in China. A member of the Chinese Academy of Sciences (Yaojin Peng) presented the laws, regulations and ethical codes in this area. While explaining that the country had “accelerated” and “improved” regulation, he pointed out that hereditary gene editing is legally prohibited and that China is basically “compliant” with international standards. The next presenter (Joy Zhang, a sociologist at the University of Kent) was less optimistic. While discussions of safety and ethics are welcome, these would only apply to medicine and public science, but not to corporations. In China, the participation of scientists in decision-making – these first requiring more transparency and public debate – remains a “fragile” process according to Zhang.
While germ cell editing is technically possible, it is ethically, politically and legally problematic, hence the current debates on its regulation. In Europe, the Oviedo convention (Convention for the protection of human rights and dignity of the human being with regard to the application of biology and medicine) prohibits it. At the World level, no country seems to authorize it, three quarters of the countries prohibit it, and only three countries have undetermined positions on the subject (Burkina Faso, Singapore, Ukraine).
At the end of the summit this year, we could still sense a certain frustration on the part of the organizers: “Remember that this summit focused a lot on somatic cell gene editing and all the enthusiasm it arouses. So where are the questions about it? asked Robin Lovell-Badge.
What access and what prices for gene therapies?
So let's get back to the use of gene editing for gene therapies.
Gene therapy is a therapeutic strategy which consists in introducing genetic material in order to treat a disease, either by taking, transforming and reinjecting cells into the patient (method ex vivo), or by introducing the vector directly into a tissue (method vitro). However, this process is complex and many clinical trials have experienced failures in the past.
The development of gene therapies requires substantial investments, which raises the question of equity and access to treatments. Many are those who point the finger at the very high prices of certain products existing ones: it is necessary to spend several million euros for certain gene therapies (such as Zolgensma ou libmeldy).
Hence the need to think about price regulation or alternative non-commercial models (philanthropy, consortia between university actors, so-called “humanitarian” licenses). Patient associations have an important role to play here, because they are not only interested in the development of these therapies, but “address their economic barriers and explore solutions they deem desirable or just for patients and society as a whole”.
The arrival on the American market of a treatment for sickle cell disease raises many questions: “I don't know how we can create prices, payments, innovations in intellectual property […]. A treatment for sickle cell disease is coming this summer, but no one is ready," said Steve Pearson, president of the Institute for Clinical and Economic Review, at the summit in London.
Too high prices for gene therapies entail the risk of a “technical eugenics”. How to avoid that the treatment is only accessible to the richest? How to ensure fairness at the international level and that the treatment is affordable in the regions of the world where the disease is frequent (sub-Saharan Africa, Antilles, Brazil, India)?
Human gene editing therefore raises a whole range of questions: scientific, ethical, political, societal, regulatory, economic and democratic.
Faced with these challenges, more concrete responses will have to be found in terms of governance and regulation. How to translate principles such as accountability, transparency, accessibility, equity, inclusion, and societal dialogue into political imperatives? How, roughly, do we take the politics of genetics seriously? The stakes are high.
Morgan Meyer, CNRS research director, sociologist, Mining Paris
Image Credit: Shutterstock / Yurchanka Siarhei