Genetics As All Important–3 Parent Reproduction

Yesterday I noted that one of my two topics was an exploration of the incompatible (?) views of the importance of genetic connection in relation to parentage apparently held by those who support ART.   You can, of course, read yesterday’s post. (And probably you should read it.)   But the idea is that people who support use of and access to ART sometimes argue that genetics is all important (and therefore ART is crucial) and sometimes argue that genetics is unimportant (and hence sale and other transfer of eggs and sperm is just fine).

Here’s an example of the former.   This morning the British Parliament approved the use of IVF employing genetic material from three people.   Apparently Britain is the first country in the world to do so.

The idea here is that you might have a woman who carries some genetically heritable disease in her mitochondrial DNA.   If she is to reproduce using her own genetic material there are only two options.  One is to pass the defect to her child.   The other is to use mitochondrial DNA from another woman who does not have the same genetic defects.   (You can read about the process in more detail in earlier posts–search for mitochondrial DNA.)

I won’t take the time just now to discuss the risks and objections to the procedure.  That’s not my current point.  My point is merely this:  approval of this must be grounded on the belief (stated or otherwise) that it is very important that a woman be able to have a child who is genetically related to her (in the main, anyway).  So important that whatever the objections are, they do not outweigh her interests.

This is one instance where the “genetics is critical” argument is used and is used to great effect.  (The vote wasn’t that close.)     But many of the same people who make and use this argument have no trouble with the transfer of genetic material (eggs and sperm).   That’s what I intend to explore so I thought I’d just toss this out to get underway.


12 responses to “Genetics As All Important–3 Parent Reproduction

  1. Welcome back! I’m still very uneasy about fiddling with an egg, seems like the potential for problems (said by someone with no qualifications). Are there any guaranteed to be passed down genetic diseases in every single egg that would require this to be done vs. genetic testing on the egg or embryo?

    • I’m not an expert either but my understanding is that there are some women who have defects in their mitochondrial DNA (if I’ve even got the name right) that would be found in every one of their eggs. The technique at issue here takes the nuclear DNA from these women (which is presumably fine, but I can see that this might be open to question in some instances) and insert it into an egg that was taken from a different woman who has no mitochondrial DNA issues. That egg would have had its nuclear DNA removed, so you’d end up with one egg with the nuclear DNA from the first woman and the mitochondrial DNA from the second.

      Certainly some of the opposition to the technique arises from lack of confidence that this can be done safely and reliably. And some arises from concerns that there may be unknown consequences. And some arises from general moral objections to this sort of engineering. And I’m sure there are other bases as well.

  2. It bothers me that this is called 3-parent reproduction. Unlike surrogacy or other forms of ART, injecting the nucleus of one of a wife’s ovum into a stranger’s denucleated ovum and then fertilizing that with the husband’s sperm does not seem to have any significant impact on the actual genetics of the embryo. The wife’s defective mitochrondria are in the cytoplasm of the ovum, outside the nuclear envelope so extracting that nucleus does not transfer any of the bad mtDNA (I’m not a geneticist so maybe I’m oversimplfying this but it doesn’t seem like many people understand much cell biology). I have a lot of empathy for this kind of reproductive choice. more so than the choice of an anonymous gamete. The woman with mutated mtDNA is often faced with a birth of a child who is not equipped to thrive, especially since the proteins created by mtDNA are related to ATP production within cells, essential to the energy needed for cellular growth. Such a child is left without a future and a painful early death. One possible trait that is inheritable from a mtDNA mutation is blindness but no egg donor who has that observable trait would be chosen for this procedure. If I understand the procedure, there is no destruction of any embryos, as opponents have suggested, only ova. Since most ova do not reproduce if unfertilized and die at the rate of one month, where is the ethical dilemma? There are only 37 genes in mtDNA, few or none of which are related to inheritable traits, mostly for the production of proteins to build new organelles, more mitochondria and the production of energy from ATP. The fertilization of the egg’s nucleus – not the mtDNA – by one sperm and the resulting embryo is the actual genesis of a new human being, a recombination of over 21,000 genes from both parents. Those chromosomes do not undergo meiosis with the mtDNA, in the mitochondria, which is a primitive self-replicating cell, much like a benevolent virus. All the character of the new embryo comes from Meiosis of the two gametes of the parents. There is certainly some risk of not knowing consequences for the child. But we do know the sad consequences of a woman with damaged mtDNA. It seems far more problematic that donor conception involves the risk of not knowing the consequences of over 21,000 unknown genes from an anonymous gamete and whatever harmful mutations or recessive traits they carry. Also, the high costs and procedural risks of egg retrieval and IVF are already undertaken all the time. How is this any different?

    • Your explanation of the technical details matches mine, and I see your point about calling it “three parent reproduction.” Perhaps the most you can say (as I understand it) is that the mtDNA would be passed along by a child to her children, and it is part of the child’s overall genetic make-up, albeit a small part.

      Reading your comment I find myself thinking that this is a place where attachment to the idea of genetics being critical maybe has lead us to an overly simplistic characterization of the process. The fact that some small part of the overall DNA is present leads to calling it “three-parent DNA” because we view genetic connection as an on/off switch–it’s there or it isn’t–and the provider of the mitochondrial DNA either is therefore a genetic parent.

    • Now I was under the impression that the MDNA donor would show up as the mother in a dna test for maternity and that the wife with the bad dna would not. It does not matter how little it is it’s the dna of the mother so she would be the one who has the maternal relationship the father with the paternal relationship and I’m not sure what relationship the wife would have being neither maternal or paternal

      • I’m not sure that is correct. I think it is more common to test regular DNA when establishing genetic parenthood, in part because family members would share virtually identical mDNA. mDNA testing is used to trace ancestry. But someone who actually knows should feel free to correct me.

        I think the language problem is there because we often use language imprecisely. Thus we often say “mother” without being specific about whether we mean genetic mother or social mother or legal mother. (Maybe we mean al of those sometimes, too.) We can describe one woman as the source of the mDNA and the other as the source of the nuclear DNA and then worry separately about resulting legal and/or social relationships, I think.

        • Well for the purpose of establishing legal kinship and for people knowing who they should not be reproducing with – should they have a kid with that mdna donor themself would that be the same risk as any parent reproducing with a child? Would the mdna donor’s kids she had who are 50% hers including the mdna be bad for these people to have kids with?

          • I think–but I probably should say THINK to emphasize that I do not know–that mDNA is not significant in terms of concerns about recessive genes and the like. You only get mDNA from one parent in any event.

          • Re: m’s question about the child mating with the mtDNA donor’s child. This is not really consanguinity since the donor’s marital child has no shared genes with the child of the couple resorting to mitochondrial spindle transfer. There is no increase of risk of these two having the same genome (they absolutely don’t have the same genome) and then creating a child with an autosomal recessive gene because having so many shared recessive genes (they wouldn’t have any at all, in all likelihood). That risk would be the same as in any mating.

      • Probably so if someone was doing just a mtDNA search on a web site like 23andme. However, the more successful kinds of searches are not mtDNA or Y-DNA but are autosomal. In an autosomal search you would be looking at all the matches from the 23 chromosomes of both parents genomes and any mtDNA showing up is miniscule compared to the full individual genome. The child’s genetic relationship with the mother remains intact as well as the father. I know you are searcher for other people so if you recommend an autosomal search on one of these sites, it would lead to many more matches. If they can afford it, searching on three different sites, like FTDNA, 23andme, and ancestry will give them a broader database for success since most people only test on one site. If they do just one, then they will be missing matches from the other two. Then combining the information with info from other traditional search sources will be amplified. That is what I did and I determined my genetic father through FTDNA and then eight half-siblings when I expanded my search to all three plus doing some genealogical data search FamilySearch (LDS genealogy site) on these matches. In that way, I was able to learn much more about some of my ancestors and extended family. Eventually, I matched with one of my genetic father’s granddaughters who gave me an entree into actually meeting my gene father’s marital family as well as two first cousins and two second cousins (who I already knew as friends but did not suspect as relatives). I also found out a great deal about my unknown relatives on my mother’s side through ……….
        As I said before here, anonymity is doomed. ART professionals, gamete donors and ART parents need to realize that the child may find out the truth no matter what everyone else does to hide it, even if the child does not suspect anything. Who would be able to stop a curious teenager who tests on one of these sites for health or genealogical information and then discovers unexpected paternity or maternity? The truth will out.

  3. I got this wrong. There is no actual nucleus in a woman’s egg. Sperm goes through meiosis and creates gametes throughout a man’s life, billions of them. They are ready to fertilize a woman ovum. Although men have mtDNA, it is not transferred by the sperm since all mtDNA come from the mother’s ovum. Females develop all the ova, around 400, that they will ever have during the first three months of existence. These primary oocytes are developed though mitosis and then all the ova begin the process of becoming gametes: meiosis. The process is suspended at the beginning of prophase I. They remain suspended in that state within the ovaries until each one is released, one at a time during ovulation but do not begin the rest of the meiotic process until a sperm fertilizes the oocyte which then completes the meiosis process. TMI, I know, but the point is that there is no nuclear membrane in an unfertilized ovum, just all the chromosomes in spindles within the cytoplasm of the cell, along with all the other organelles, including the mtDNA. However, these “maternal spindles” can be removed from an extracted ovum without extracting the mtDNA from a damaged ovum and transferred to the healthy donor egg (also retrieved) from whose spindles have also been removed. Then, in a petrie dish, the intended father’s sperm can be placed for fertilization just like any IVF, so that a zygote can then be created. Apparently they have done these processes already and have let the zygotes develop into a blastocyst and frozen, awaiting Parliamentary approval in the U.K. So no destruction of an embryo is done, and no one can complain that there is a human life destroyed. In fact, many gynecologists believe that a fertilized egg does not become an embryo until the blastocyst attaches to the endometrial walls, several days afterwards. Others claim that an embryo isn’t life until much later. This is called mitochondrial spindle transfer. An alternate is called “pronuclear” which involves fertilizing both the intended mother’s ovum and a donor ovum with the intended father’s sperm. Then when the developed nucleus occurs in both embryos, the nucleus is taken from the “bad” ovum and implanted in the healthy denucleated donor embryo. This latter is more ethically problematical to some people. In either case, the report of the Nuffield Bioethics Organization says that the egg donor cannot realistically be called a third parent, since the child will have a genome coming solely from his parents, plus some minor mtDNA that has no affect on the child’s genetic characteristics.

    Sorry for the misunderstanding.

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