Still More on Gene Editing

Joe Gibes (May 9) and Steve Phillips (May 13) took up the challenge I posted last week: to address whether human germline gene editing, even in a hypothetically-narrow example case, is morally unacceptable in some intrinsic sense, and therefore something that ought never be attempted or, for that matter, pursued in the laboratory.  If you have not read their posts, please do so.

To come back briefly:  First, I agree with both Joe and Steve.  But as Steve’s commenter Carol Eblen suggested, I don’t think a majority of Americans, when pushed, would agree.  I expect the public discussion to be defined by discussions of human subject research ethics and ultimate risk-benefit projections.  As a consequence, finding some path forward, with fairly extensive regulation, will be almost an assumed conclusion, even if not stated.  I expect that what will be proposed is some sort of extension of the current regime governing human gene therapy, which is “somatic,” that is, done on fully-formed individuals.  And to the degree that gene editing could be limited to the somatic setting, that might be quite satisfactory, from an ethical standpoint.  If, to take the example I posed, a gene therapy for the Huntington’s mutation were proposed for teenagers and young adults with the mutation, that would appear in principle to be an ethical undertaking.  But I have a hard time imagining it would ever be feasible.

Steve reprised a central argument from his 2012 Ethics in Medicine paper:  the experiments necessary to accomplish clinical human gene editing could never be done ethically.  This is a powerful argument by itself, although maybe not a criticism of the technology “intrinsically.”   What I posed was, I admit, a counterfactual—a “what if?”  The problem with counterfactuals is that they are counter to the facts, divorced from reality.  As Steve reminds us, reality is not so neat.  And so my artificial example is maybe not so helpful.

Steve also argues that germline modification would change how we view children.  This is similar to the broader argument that artificial reproduction construes children as products, not gifts.  That’s the sort of argument made by Leon Kass and Michael Sandel.  The objection to it is that it’s too binary, that there are cases not so clear-cut, that prompt exceptions to the general rule.  If we were to attempt to “cure” our unborn progeny of a terrible genetic disease, we are arguably not rejecting them as defective, as we are by diagnosing them at the embryo stage and refusing to bring affected ones to birth.  But in Steve’s argument I also hear echoes of Joachim Boldt’s current caution about synthetic biology, that by allowing engineering to encroach too much on the human organism we would reclassify people from equals into classes of actors and objects. That, in turn, echoes Lewis in The Abolition of Man.

I see Steve’s arguments as a bit more consequentially-oriented, albeit not “consequentialist,” per se, than Joe’s three points.  At one point in his post Joe almost makes his first point sound like his third, but they are indeed distinct:  technologies have a life of their own, they embody an idea, and we humans can’t constrain ourselves.  All three points are powerful.  Regarding the first, a technique really dictates its applications.  Also, we should not forget Mark McQuain’s recent comments that with something as complex as the genome, we simply don’t know and cannot predict all the consequences.  Things bite back, and there are unintended consequences.  Therefore, a risk-benefit calculation is rendered meaningless, ultimately.  This was a big point in the Presidential Commission’s 2010 deliberations about synthetic biology, and has been raised by media commentators pointing out that we can’t guess the long term evolutionary implications of what looks like a simple gene edit.  (And, CRISPR is not so perfectly selective, at least as of now.)  An editorial in Nature this week makes a similar point in urging a ban on gene editing of wild animals—this from an ecological perspective.

Joe’s point that the idea behind germline modification is eugenics is hard to resist.  I would think that many would try, however.  We do argue for a “therapeutic boundary,” after all, implying that attempts to cure are not motivated by the search for human enhancement, but by mercy.  And so one could argue about germline gene therapy.  Then again, just because medical technologies may be prematurely or overly used doesn’t mean in principle that there is a place for them. 

But as Joe said, we are “incurably eugenic.”  If memory serves, when human IVF was being debated in the mid-1970’s, proponents tried to assure critics that its use would be carefully circumscribed.  Not exactly.

I do think that the public discussion of human germline editing is likely to settle on a “pragmatic” path forward in spite of objections like this, but I also think that, taken together, they form a strong set of intrinsic and consequential reasons for not even experimenting on the editing of human genes in germ cells.  The implications are so vast that they constitute a compelling “precautionary” argument, a “presumption to forebear.”

But given that the technique has been fundamentally applied, and I have suggested that its use on human somatic cells might be OK, can it be restrained at all?  Dr. Jennifer Doudna, the discoverer of CRISPR-Cas9, says that it’s too late to restrict basic research.  She’s surely right.  Check out the recent article about her from the New York Times.

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Steve Phillips
5 years ago

There is a problem with viewing germline genetic modification as therapeutic treatment of a diseased embryo. If this technique were used in the case of a couple who were carriers of a serious genetic disorder wanting to have a healthy child, any embryo with the disease would have been intentionally created with the plan to treat that embryo if the disease existed (or possibly to treat any created embryo whether the embryo was afflicted or not). The choice to have a genetically related child is being made by the potential parents because it fulfills their desire to have a genetically related child. Since any potential children do not yet exist the choice is not be made for the benefit of the nonexistent child. All the risks are born by the child and the benefit is for the parents. This is very different from an existing child being found to have a disease and then deciding to treat it which is what we eman by a treatment being therapeutic.

Mark McQuain
Mark McQuain
5 years ago

One of the side questions that this discussion brings to mind is: “How much of my genetic code can I modify and still be me?” While Steve’s point is certainly true (germline genetic modification is not a therapeutic treatment of some future, presently non-existent embryo), I am sure families would consider germline editing of their fatal genetic recessive traits “therapeutic” in eliminating the fatal trait from future genetically related offspring

There is presently medical/social pressure on families with such genetic disorders to be aware of their genetics to avoid having children with the recessive trait (Tay-Sachs is one such example of a fatal disease where heterozygous parents for the trait are encouraged not to marry to avoid such an outcome). These parents would certainly love to have a genetically related offspring, but without the specific recessive gene that causes Tay-Sachs. I think they would consider their healthy modified offspring to be just as genetically related. The big concern with all of these counterfactual hypotheticals is that we can never have all of the data a priori to run even the crude utilitarian calculation to decide if it is “worth” doing.

Tay-Sachs is one such disease that supports my concern with unintended consequences of such genetic modification. It turns out that carriers of the Tay-Sachs recessive gene (persons carrying both the healthy dominant gene and the fatal recessive gene) are somewhat protected from TB and we do not know why this is based upon the DNA sequence alone