A paper just came out in Nature yesterday entitled: “Nuclear genome transfer in human oocytes eliminates mitochondrial DNA variants.”
It’s surely risky of me to say this, but is this paper really a clinically-relevant breakthrough for mitochondrial disease worthy of a Nature paper?
The study as science is fine and very interesting, but it seems quite questionable to me to so strongly invoke clinical relevance as they do (even if they say some stuff must be discussed first):
Before proceeding with human clinical trials on the transfer of the maternal genome, it will be important to publicly discuss patient needs, ethical considerations, and to establish appropriate guidelines for the use of oocyte nuclear genome transfer in assisted reproduction.
The abstract also ends claiming clinical relevance:
These results demonstrate the potential of nuclear genome transfer to prevent the transmission of mitochondrial disorders in humans.
Finally, the paper is also discussed in a Forbes blog piece by friend John Farrell that calls it a “breakthrough”. I like John’s blog a great deal (hi, John), but I think we differ on this paper.
The claim that this has clinical relevance in the real world is at best wishful thinking.
Why am I so skeptical?
In the hypothetical context of real-world assisted reproduction, moving one oocyte nucleus into the enucleated oocyte of another person could trigger all kinds of devastating problems (most likely through epigenetic changes) that might not manifest until you try to make a human being out of it.
Then it’s too late.
30 thoughts on “My concerns about Nature paper on Genome Transfer for mitochondrial disease”
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I understand your concerns but to say that its questionable to invoke clinical relevance doesn’t jive with me. How is this not clinically relevant? To not cite the recent paper out Oregon when discussing this doesn’t seem to make much sense to me. They have made healthy monkeys by this method so this study is clearly clinically relevant. Mitalipov even says he has appealed to the FDA. And this study seems to deal with some of the issues that Mitalipov had.
And to me it seems that the authors made a good and responsible statement to say,”Before proceeding with human clinical trials on the transfer of the maternal genome, it will be important to publicly discuss patient needs, ethical considerations, and to establish appropriate guidelines for the use of oocyte nuclear genome transfer in assisted reproduction.”
I generally enjoy reading your blog but I don’t think this post really tells the whole story.
Thanks for the comment, Larry. You are right I should have mentioned the primate paper.
However, I am strongly opposed to the use of nuclear transfer in the process of assisted human reproduction because
(A) I do not believe that we as a society are anywhere nearly wise enough and ready to decide whether to create hybrid humans even if we could be sure they are “normal”, (B) I think there is an unaccetable & difficult to define risk of abnormal human development in this situation, and (C) the FDA will never approve it in my opinion. I also would argue that even if apparently “normal” people were made this way, they would not really be normal and they could pass on the abnormality to offspring. We’d have opened a Pandora’s Box. For these reasons realistically I don’t see clinical relevance here.
I would argue that there is a fundamental difference between a clinical technology to repair or correct existing people who are suffering vs using clinical technologies to create people who would otherwise not exist.
To provide context, the number of people who could potentially have been created (in the usual way) is many orders of magnitude greater than the number that have existed. The imperative to alleviate suffering of existing people is strong — and I’d go out on a limb to explore every reasonable option. The requirement for new ways to produce people is not so clear to me.
Would your concerns apply to other techniques, which serve the same purpose:
chromosome spindle transfer –
pronuclear transfer –
video-interview with Mitalipov –
Mitalipov commented on clinical readiness of this methodology:
The method needs to be tweaked to increase efficiency and gain regulatory clearance, but it is ready for the clinic, says Mitalipov. “You can expect the first healthy child to be born [using this method] within three years.”
Arthur Caplan commented on possible ethical issues:
When you change genes in an egg, even in the mitochondria of an egg, you make a change that is inherited by every single offspring of any child created from that egg. That is called germline engineering — meaning changing inherited genetic material.
And germline engineering of mitochondria crosses the line from using genetic engineering to fix our body parts into directly engineering the traits of our children. It is a road that could lead, in the distant future, toward eugenics.”
The methods are not the problem for me. The problem is engineering human beings. I agree with Caplan. Mitalipov talking about using this to make “healthy” children is really frightening in my opinion.
Turns out if you read Art Caplan’s full article (which I just did today) he is surprisingly in favor of taking the risk of use the method to cure diseases. So in that regard I disagree with him.
Paul, did you see the similar paper in Nature October 24 from Oregon Health Sciences?
I think so…was that the one done in primates?
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