Perspectives on Hinxton Human Germline Modification Statement

The international stem cell policy and ethics think tank, the Hinxton Group, weighed in yesterday on heritable human genetic modification with a new policy statement.

The Hinxton statement is in many ways in agreement with the Baltimore, et al. Nature paper proposing a “prudent path forward” for human germline genetic modification, which came out of the Napa Meeting earlier this year.

However, while several of the Napa authors have now thrown their public support behind a clinical pause or moratorium on heritable human modification (e.g. Jennifer Doudna as well as David Baltimore and Paul Berg in a later piece in the WSJ), Hinxton didn’t explicitly address either positively or negatively the question of a moratorium.Hinxton Group on human genetic modification.

My initial reading of the Hinxton statement is that I mostly agree with it. In my own proposed ABCD plan on human germline modification from earlier this year, however, I included at least a temporary clinical moratorium.

I also would have appreciated a more detailed risk-benefit analysis in the Hinxton statement. For instance, I didn’t see a discussion of specific possible risks in their statement. Via my own risk-benefit analysis, I come to the conclusion that on the whole a temporary clinical moratorium has the potential for far more benefit than harm.

What would be the specific, possible benefits of a moratorium?

If the scientific community has united behind a moratorium on clinical use not only will that discourage rogue or potentially ill-advised stabs at clinical use, but also if a few such dangerous efforts proceed anyway (which is fairly likely) and come to public light, these unfortunate events will be placed in the appropriate context of the scientific community having a moratorium in place. Therefore, a moratorium both discourages premature and dangerous clinical use as well as putting potential future human gene editing clinical mishaps into the proper context for the pubic.

Another potential benefit of a moratorium is that it could discourage lawmakers from passing reactionary, overly restrictive legislation that bans both clinical applications and important in vitro research. It would give the politicians and the public the right sense that the scientific community is handling this situation with appropriate caution. If you don’t think that a law on human germline modification is likely in the US, consider that conservative lawmakers have already proposed such a law be included as part of the pending appropriations bill and Congress a few months ago held a hearing on germline human modification.

Other benefits of a moratorium include that it would a) demonstrate to the public that the research community is capable of reaching consensus about important ethical issues and b) increase accountability within the research community. Any rogue researchers or clinicians who would violate the moratorium, even if it were not illegal for them to do so, would at least be subject to the disapproval and possible sanction of their professional peers or institutions. Without a moratorium in place, it is far less likely there would be these kinds of consequences.

What about risks to a clinical moratorium? The primary possible risk of a clinical moratorium is that it could, should human heritable genetic modification someday down the road be viewed as a wise course to pursue directly, impede clinical translation. This warrants discussion, but in my view the risk here is somewhat reduced by the possibility that continuing basic research develops a compelling case that a blanket clinical moratorium might no longer be needed.

The other risk here is that a moratorium on clinical use also might in theory discourage some potentially valuable pre-clinical research as well. In other words, some researchers may adopt the mindset that if they cannot get to their ultimate goal of making clinical impact, why do the preclinical studies? I expect that many researchers would instead go ahead and do the preclinical work with the expectation that a clinical moratorium could be lifted and in fact their own preclinical work might help build a case for moving beyond a moratorium.

I agree strongly with Hinxton on the need for continuation of basic science on CRISPR and other gene editing technologies limited to the lab. In my view, we should have a nuanced policy though, whereby we support continuation of gene editing research in human cells and even in some cases human embryos in the lab under specific conditions (see again my ABCD plan for details), but in which we also put an unambiguous hold on clinical applications at this time.

In the absence of a framework that includes a clinical moratorium, we probably do not have the luxury of a reasonably long time frame (e.g. measured in a few years) for open discussion to sort things out carefully. To be clear, open and diverse discussion is crucial, but we just do not have a whole lot of time to do it as things stand today. Why? In the mean time absent a moratorium, I believe that some will go ahead and do clinical experiments on human germline editing. This would not only put individual research subjects at risk, but also pose dangers in terms of public trust and support to the wider scientific community. In a relatively permissive environment lacking a clinical moratorium, one or two instances of rogue researchers clinically using gene editing in a heritable manner could end up leading to a backlash in which even in vitro gene editing research is stymied.