“The Power of Three”

That is the title of a news piece accessible at Nature’s website this week.  It refers to something that Steve Phillips and I posted on back in February; to wit, the potential for “three parent babies” resulting from the transfer of a nucleus (and its genetic material) from a diseased mother’s egg cell into the enucleated egg from a healthy donor.  (I am skipping important technical nuances with that description; see the Nature article for at least a partial description.) The disease(s) in view are mitochondrial diseases, rare but devastating disorders resulting from abnormal mitochondrial genes, of which there are all of 37, compared with on the order of about 20,500 human genes overall.   Human sperm transmit no mitochondria to offspring, so mitochondrial diseases are inherited from the mother.

The Nature piece, while far from complete, is a pretty good introductory discussion of the work for the general reader.  It briefly addresses some, but not all, of the implications.  The subtitle says that this work is “on the verge of clinical use” in the hope that women with mitochondrial diseases might be able to bear unaffected offspring.

I count at least 10 ethical issues raised by this work.  There may be more.  Steve and I touched on several in February, but the Nature article offers the occasion to try to list them briefly.  I don’t pretend the following list is complete, and space prevents me from trying to address them.   Also, there was an excellent piece last year in CBHD’s Dignitas, which I cannot lay hands on, and could not do justice to, here, in any event.

First is the question of risks to any immediate offspring.   It is not clear that the egg modification process will eliminate diseased mitochondria, or avoid further complications, including, conceivably (apparently based on work in mice and fruit flies) other genetic or general disorders not directly related to the mitochondrial defects.  As Steve and I commented in February, these risks are far from fully understood.

Second is the question of informed consent.  The unborn, much less the yet-to-be-conceived or yet-to-be-implanted, obviously can’t provide informed consent.  The intended mother would have to do that.  That’s not necessarily outside the pale.  Presumably a child otherwise destined to be afflicted with these disorders would be willing to take considerable risks to try to avoid them, and in any event existing regulations allow more-than-minimal risk research in pediatric populations if there is a sufficient prospect of direct benefit to the subjects.

Third is the question of whether there would be any risk of inherited disorders to the second generation—the offspring of the “treated” child.  Researchers in the US have followed two generations of monkeys after the sort of nuclear DNA transfer envisioned, and report they appear normal.  Some scientists would want to see many more generations.

Fourth is the possible strategy of sex-selective abortion to try to prevent the concern raised by the third issue.  One presumably would want to have only boys born of these procedures, to try to interdict any subsequent maternal transmission.  This assumes that the boys’ genomes are not adversely affected in the process.

Fifth is the practical fact that, to perfect the nuclear transfer technique, it would be considered advisable to do substantial practice with human eggs and sperm—i.e., create human embryos solely for research purposes, and of necessity subsequently destroy them.

Sixth is the commodification issue.  The eggs developed would be considered a form of cellular therapy, and be subject to strict manufacturing controls.  Presumably each case would be unique, so that buying and selling would be limited to compensation of the healthy egg donor.

Seventh is a form of the “slippery slope” worry—that the technique is broadened to become a treatment for infertility (already actively contemplated).  This is a concern in that it further commodifies reproductive medicine, and that it portends other ambitious extensions of the genetic modification of  humans.

Eighth, and related, are the broader twin concerns of confusions about parentage, and the wisdom of opening the door to introducing heritable changes on purpose into humans.  There is both the more consequentialist perspective on this—do we know what we are doing?—and also the concern that choices about introducing the technician so much more intimately into the outcomes of reproductive choices.

Ninth is the fact that all this is coming with relatively little discussion in the general public.

Tenth is a type of justice issue—this won’t be cheap.  Why this and not some other use of our resources?

Now, a difference of 37 mitochondrial genes is not going to make someone wonder who his mother really is.  Perhaps this would be one thing if we could be assured that we can establish a narrow scope and firm boundaries around this work, in the name of observing the “therapeutic boundary.”  But experience shows that such boundaries do not hold.

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