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05/08/2015

Gene Editing—Trying to Get Specific

In a comment last week, Mark McQuain pointed out the article “Engineering the Perfect Baby” in the MIT Technology Review.  Freely accessible online, it describes, in non-technical terms, several of the routes that genetic editing may follow.  Perhaps the most explosive:  adult skin cell transformed into an induced pleuripotent stem cell that then is used to give rise to germ cells that are then genetically edited.  (Note that a treatment for infertility can be envisioned by this route, possibly not requiring any gene editing.)  Nearly everyone speaking publicly is calling for a moratorium on attempts to bring a genetically-edited human to birth.  Some expand that to call for a moratorium on the basic research into altering germline cells.  Reasons for their positions vary, but there are enough committed enthusiasts that basic research is likely to go forward.  Read the article.

Courtney Thiele and Steve Phillips commented insightfully on Lewis’s The Abolition of Man.  Steve’s 2012 article in Ethics and Medicine is a reminder of how much has already been written about the ethics of germline modification.  Read it if you can get it.  (Steve sent me a copy directly.) 

But there is a risk in focusing too much on “enhancement,” rather than on germline modifications to prevent/treat/eliminate certain genetic diseases.   And that risk is this: the technology can no longer be easily dismissed by virtue of its being far off in the future.  It is pretty much here.  So the question is:  is it everywhere and in all cases morally impermissible, in principle, to alter the human germline, or would a general moral prohibition admit of exceptions?  Were it possible to safely and truly selectively edit out the Huntington’s disease mutation, for example, in sperm, eggs, or intact human embryos, and make the process available to all who need it without regard to ability to pay, would we not embrace that?

I readily admit the counterfactual here.  From the standpoint of human subject research alone, any attempt to do what I just suggested would make for a lively IRB discussion for the foreseeable future.  But such objections were the most prominent ones posed against human IVF in the 1970’s.  Then Louise Brown was born.  Were the safety issues ironed out, would we fundamentally object to any inheritable alteration of the human genome (as one might hold that IVF is, by its nature, morally suspect)?  Or, does it depend?  And if it depends, how many “indications,” to use the pharmaceutical term, make the list?

Some proposing caution about human gene editing make this argument:  There is another, safer way—preimplantation genetic diagnosis, or prenatal diagnosis, with non-implantation or abortion of affected individuals, bringing only the healthy to birth.  Many conservative ethicists object to this alternative on the grounds of sanctity of human life.  I suppose one might ask whether gamete selection with regard to the gene in question might become possible.  I don’t know if that could ever be feasible.  It is tempting to think so, if it is possible to identify and correct a genetic defect with CRISPR, and verify that the repair had succeeded.  But again, I don’t know.

I think the “unknown unknowns” objection is a powerful argument.  (See Mark McQuain’s comment to my April 30 post.)  But what data would be needed to lay it sufficiently to rest to support some limited clinical applications?  In principle, could those data be obtained? 

Is there some short list of modifications that, if adhered to, would absolve the biotechnologist from the charge that she is one of Lewis’s “conditioners?”  Do any and all germline modifications in principle constitute “Nature’s conquest of Man?” I could imagine a “no” answer to that question being affirmed at some point in the future by many if not most “social conservatives.”

If some germline modifications could be embraced on moral grounds, then there would be no reason to presume to try to put a full-on moratorium on the basic research.  Regulation would be called for, after appropriate “public discussion.”  The editors of Nature called for such discussion this week.  They said last year’s WHO discussion about Ebola clinical research was a good example.  I’m not so sure; the report took a while to become public, was not all that detailed, and the detailed discussion was not all that well-covered by media.  The PCSBI’s process is admirably public, but how many people pay attention?

If, however, no heritable germline modification is acceptable in principle, then we could argue that even the basic research should not be permitted (assuming it could be stopped in practice).  Or, if no ethical experiment can be designed, the research should not go forward.  (Consider human neural stem cells in mice, or Hubertus Strughold, for example.)

I realize I am rambling here.  But I worry that fear of a dystopian future with engineered superintelligent kids of rich people, based either on Lewis or on what I understand to be the Continental concern about destroying human equality by subjecting human biology to engineering, is insufficient to address the renewed task that the current developments pose.

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