The Proposed Moratorium on Clinical Human Germline Editing

As most readers of this blog will know, last week Eric Lander and seventeen others (all seem to be biologists) published a commentary in Nature arguing for an immediate moratorium on clinical human germline editing. (For short, I will call this the Lander proposal while fully acknowledging the other authors.) The Presidents of the U.S. National Academies of Science and Medicine (Victor Dzau and Marcia McNutt) along with that of the Royal Society of London (Venki Ramakrishnan) chimed in to endorse the call. The prestigious Presidents proudly noted that their organizations “are leading an international commission to detail the scientific and ethical issues that must be considered, and to define specific criteria and standards for evaluating whether proposed clinical trials or applications that involve germline editing should be permitted.” The Presidents were very happy that the World Health Organization is carrying out a parallel effort. Al this talk. But is it necessary? And will it lead anywhere new, especially given that the U.S. academies have already held two summits in 2015 and 2017 and issued a comprehensive report on human gene editing.

There is much in the Lander propsal that I admire. It does not gloss over the complexities of predicting the consequences of gene editing, especially the many scientific difficulties that are ignored by most bioethicists of both stripes (those who would prohibit and, especially, those who support germline editing—I have Suvalescu in mind). In particular, there is a welcome realization that genes act in concert and in context. One example from the proposal will suffice. We may choose to use gene editing to introduce an allele for the SLC39A8 gene that is believed to decrease risk for hypertension and Parkinson’s disease. Yet a 2018 report points out that, because of pleiotropy, the same allele is believed to increase risk for schizophrenia, Crohn’s disease, obesity and, possibly, other diseases. When would it be beneficial to introduce this allele? Because of our relatively poor mechanistic understanding of what this allele would do, we simply don’t know. (This example also shows how the distinction between negative and positive eugenics does not map cleanly to that between genetic enhancement and correction—but I’ll say more on this in a separate entry.)

For all its contributions, I still think that there are three reasons why the Lander proposal should not form the basis for policy on human germline editing. It puts unnecessary restrictions on the use of technology that could eliminate incurable genetic diseases entirely. At the same time it is unduly permissive of what it envisions because it allows each country to modify the human gene pool as it chooses for itself in accord with its cultural preferences. Though the proposal tries to pay attention to social issues, it also ignores the most important of the structural problems that make any germline modification suspect: that choices will likely reflect social power relations rather than universal human values.

The Lander proposal calls for a five-year voluntary moratorium to be adopted by all countries during which the clinical use of germline editing would not be permitted. During that period scientific and social issues about safety, efficacy, and desirability should be worked out. After that, each country would be left to formulate its own policy so long as it gives public notice, engages in international consultation, carries out a transparent evaluation of what it proposes to do, and shows that it has widespread internal social support. The proposal recognize that the questions that must be broached may be quite different between contexts of correcting deleterious genes and those of carrying out genetic enhancement.

My first problem with the proposal is that the five-year period is both artificial and, in some cases, unnecessarily long. There is a small but not irrelevant set of diseases which are caused by single genes that have no effective treatment and have high penetrance (that is, the conditional probability of manifesting the disease given the allele is close to one). These include cystic fibrosis, Huntington’s disease, and muscular dystrophy. Unless we are unwilling to tolerate germline editing under any circumstances, there is no rational ground to deny the desirability of removing these genes from the human population, and to do so now.

Of course, that does not solve the issues of the safety and accuracy of the new gene editing technologies including the much-touted CRISPR-based ones. However, as I noted earlier, the U.S. National Academies have already published a report on theses issues in 2017. The general concerns about technological safety and efficacy are well known and it is highly unlikely that anything new will emerge from five more years of discussion. What is not known is how safe and effective each individual attempt to modify a single targeted gene will be.

So, it seems to me, a rational strategy would be to establish strict criteria to identity appropriate targets for germline modification such as the diseases mentioned earlier. Next very stringent criteria should be established to demonstrate success at meeting safety and efficacy standards. Once these conditions are met, and only then, germline gene editing  should be allowed to proceed. It may take less than five years to meet these conditions for a particular gene but it may also take a lot more. But we should not have an artificial time limit.

This is not a carte blanche for human germline editing. Rather it is a proposal to permit it now for a very limited set of genes that, acting singly, cause untreatable diseases. Of course, this proposal will not be acceptable to those who would not permit any human germline editing but that disagreement will likely remain for a long time, well beyond the five years.

But, what about those diseases in whose etiology known genes are implicated but several genes may be involved and with low penetrance? Would five years of discussion be helpful in these cases? I doubt we would get anywhere beyond the two meetings that the U.S. National Academies have already held and the report that they generated. What seems most appropriate to me is to allow germline editing in the simplest cases and use the results to frame policy of these more complex situations. We should not permit anything else until we get those results. Another round of discussion at present seems like a repetitious waste of time.

The second problem with the Lander proposal is that, in the long run, it would allow some countries to choose genetic enhancement of what is supposed to be intelligence (I have Singapore in the 1980s  in mind), or of fairer skin (I have India in mind), or of sporting ability, or whatever. The only constraint would be to consult with the international community which seems to me to be a recipe for pious irrelevance on the part of international stakeholders.

With germline editing we are talking about the future of the entire human species. We live in a world that is mingling and globalizing rapidly and will continue to do so irrespective of narcissistic wall-building (and you know whom I have in mind). Given the inevitable global future for humanity as a whole, the Lander proposal amounts to an endorsement of illegitimate cultural relativism rather than an attempt to articulate, promote, and defend putative universal human values. The proposal does not even offer any reason why countries are the appropriate normative units for these discussions or how relying on them would not endorse the worst of cultural prejudices. (Of course, focusing on countries makes sense from a policy-making perspective but what we should not forget is that, with human germline editing, we are engaging with some of the deepest ethical questions about the human future. When necessary, we should be willing to move beyond these kinds of political constraint.)

Third, the Lander proposal also does not address the issue that, especially when it comes to genetic enhancement, what may be regarded as desirable will typically reflect social power relations rather than universal human values.  In my case, I am convinced that, in general, what a culture finds desirable mostly reflects its social power relations. For instance, in India (where I am now writing), pale skin embodies the worst of prejudices promoted by the Hindu caste system. I suspect that, in an society, parents would choose genetic enhancement in their children to put them at an advantage given the power relations dominating that society.

There is an interesting side issue here that I will leave aside in this entry: genetic enhancement, in ourpresent socioeconomic context, reflects individual power asymmetries and preferences whereas gene elimination is a population goal that avoids this problem. Gene elimination is easier to defend than genetic enhancement. In any case, addressing these issues will require a global discussion that may well last longer than five years. Meanwhile, the wisest policy may be to disallow germline genetic enhancement altogether.

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