In-vitro genome editing: no chance for a moratorium?

A 18-strong group of scientists from seven countries, including the US, China and several European countries, published a statement on March 14th in the science journal Nature calling for a moratorium on heritable genome editing. This document highlights how heterogeneous scientists’ positions on the topic can be. Some aspects of the issue are left unsaid, and a number of “star” biologists did not sign the paper. As the shockwave created by Lulu and Nana’s birth slows down, different stakeholders’ positions are becoming clearer. Let’s try to map their current stances.

A Who’s Who of Genome Editing

The interactive data visualization below displays the main actors of the controversy on the use of nucleases on human germline cells. It can be reodered according to different criteria, such whether they have signed previous statements (HGE Summit 2015, Napa Group) on the topic, their field of origin, or mother tongue.

Comparing actors highlights how they can align (or how they don’t) each time a new facet of the controversy arises. For example, Nobel Prize laureate David Baltimore signed the 2015 statement, but recently said in an interview that he was against a moratorium.

Germline genome editing: from basic research to applications

This last call for a moratorium targets a very precise domain: implanting modified human germ cells (ovocytes, sperm or embryos) so as to trigger a pregnancy. The best tools to do that are currently nucleases, and more specifically CRISPR-Cas systems.

The context is obviously very specific. The call first argues that the birth of Lulu and Nana shows such experiments are feasible, and that American scientists who were aware of this “clinical trial” chose not to disclose its existence publicly. But then, why ask for a moratorium on such trials when the Chinese authorities judged it was against the rules? And most importantly, when the vast majority of academic and political statements on the matter were already against implanting modified embryos?

Other arguments are even weaker. Quoted are the ideas that institutional statements since 2015 would have questioned the importance of a large consensus on such matters, or that the public interest in favor of genetic augmentation would have suddenly skyrocketed. Other collateral issues are left unadressed. Some of the scientists who signed this call are still locked in a patent warfare situation to assert their intellectual property on CRISPR-Cas systems. A moratorium would delay clinical trials on in-vitro interventions, which would therefore void any risk of opening another frontline in this battle.

A wobbly device

The arguments in favor of a moratorium are therefore far from being adamantine. On the one hand, the text alternates between using the words “nations” and “governments” in order not to mention the traditional “States”, the moral entities able to sign treaties and enforce its conditions on their territory. One has to acknowledge that the UNESCO and Oviedo conventions, which have binding effects for some countries (and effectively answer to the objectives of the call for those) were not able to establish themselves as international standards. On the other hand, leaving “nations” free to build their own model would be relying on the ability of States to self-limitation, which they are notoriously bad at. While Ulysses was able to bind himself to the mast to survive the Sirens, even respectable States sometimes try to infringe on their Central Banks’ independence, which is the closest example of State self-limitation one can find.

The call for a moratorium asks for three main provisions. After a fixed five-year period during which all trials would be blocked, any country considering them would have to publicly acknowledge its intent to do so. It would then have to evaluate to what extent such trials are relevant to the therapeutic need formulated, and ultimately check that the domestic social consensus is wide enough to permit the trial.
The authors sum up their stance with the following sentence: “the common principle would be all nations agreeing to proceed deliberately and with due respect to the opinions of humankind.” It implies that the aforementioned steps would enable the “respect to the opinions of humankind” to grow insofar as to become a binding rule for all. Can we conclude that a common, “universal” sense about the possibility of editing humans would thus be created?

Finding another way

The fact that many personalities did not sign the call is another hint its proposals are far from being consensual. While being de facto impossible to enforce, it could become another weapon wielded by actors who are actively hampering research. Such actors, who existed far before the emergence of synthetic biology fought against abortion rights or GMOs and have found a new battle in opposing life science research in CRISPR.
Other institutions, such as the recently formed WHO committee, suggest creating a central registry on active research in this particular field (germline genome editing). Creating such a database might seem to be a good idea, but it doesn’t solve the issue of scientists and laboratories who decide not to abide by the rules, which means to not publicly acknowledge the actual range of their research.

Of course, building binding frameworks of rules is a tough job. Forbidding a practice in a country often results in making it a market in another. Transgressions to established rules are virtually impossible to prevent: babies have been born through IVF combined with mtDNA or CRISPR interventions before any State could detect them.

Is it therefore impossible to regulate the use of nucleases in-vitro? Maybe not. Rather than indefinitely mourning the failed international mechanisms (such as the Oviedo convention or the International Criminal Court), one should try to build with bits and pieces taken from functional institutions.

A multilateral regulation agency

One of the recurring proposals comes from the famous geneticist George Church, according to whom States should be able to track gene editors by giving them a permit. He uses the driving license metaphor: if we can be confident you won’t use your car to kill people, the same should apply with a nuclease. The comparison has obvious limits. Do we really want to give the government, politicians, the executive power, the ability to allow or disallow this or that research? To validate this or that researcher or laboratory? Are our democratic mechanisms strong enough to manage and withstand that kind of power? The trend of the last decades has been to do the exact opposite. Independent agencies build a cutting-edge expertise on the sector they regulate, and therefore ensure a relative stability of the rules on the matter, and are identified interlocutors with which actors can engage.

The FDA has shown a credible ability to keep up with the pace of biotech innovation. In Europe, the Commission’s Direction de la Concurrence (Directorate for Competition) has mustered the clout to face both the financial power of mega-corporations and States’ political interference. If levelling clinical trials is still an objective that might prove hard to reach, the EU and the USA could collaborate in creating a multilateral agency that would set the standard in tracking the tools necessary to use nucleases. Rather than tracking scientists, it would start by tracking the reagents and the machines.

That could start with the certification and registering of the companies producing those, as well as their clients. It could be also extended to sequencing capacities, which prove to be an important link in the chain. Few counties will de facto be able to opt out of such standards, which would end up being necessary to any kind of scientific or industrial collaboration.

That doesn’t solve all problems. It would still be possible for a country to develop a complete autonomy in genome editing as to pursue its own national goals. No authority could counter those developments, as sovereignty of the country would prevail. But it is worth noting no country appears to show any will to engage in such a path.

A French version of this text was originally published on The Conversation (France)

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