Update on Three-Parent IVF

For some time now I’ve been following a new ART technique that is being developed in the UK.   It’s back in the news again and since it fits rather nicely with a topic I raised yesterday, it seemed like a good time to revisit the topic.

You can certainly go read the explanation, but here it is in a nutshell.   A small number of women with healthy nuclear DNA carry defects in their mitochondrial DNA.  If the eggs from these women are used for reproduction there’s a chance that the offspring will have genetic disorders transmitted via the mitochondrial DNA.  (There’s a small number of those, but I gather they can be severe.)

It is possible to take the nucleus of an egg from one woman place it inside a hollowed-out egg from a different woman.   You can do this where the first woman has defective mitochondrial DNA and the second woman does not and you end up with an egg that has entirely healthy DNA.  Of course, it would also have DNA from two different women.   If it is then fertilized you could create an embryo (which may ultimately become a child) who has three genetic parents–the two women and the man.

The news now is that the HFEA (the UK regulator of ART) has concluded that more work needs to be done with the techniques used here before they can be approved for clinical use.   The concerns of the HFEA expressed here seem to have less to do with the ethical issues raised, which will not be addressed by more testing and experimentation, than with the safety issues.   Given the comments of the scientists involved, it seems to me that the point at which the techniques will be approved for clinical use is not so very far off.

Like ICSI (the subject of yesterday’s post), this technique gives people a new way to become genetic parents.   Indeed, that is really its sole value—women with defective mitochondrial DNA can, at this point, only become genetic parents with some risk to the child.  If and when this technique is approved, they will be able to become genetic parents without risk to the child (or more accurately, with only whatever minimal risks the HFEA decides are acceptable.)    Thus, these women will be able to become genetic parents, just as ICSI has allowed men with inadequate sperm or inadequate supplies of sperm to become genetic parents.

Now here there is an added wrinkle.   The women who use this technology will, by definition, be people who care a good deal about genetic relationships.  If they didn’t care, they could simply buy an egg.  (I suppose I am making an assumption here that this system will have an added cost, but I think this is a fair assumption.  You still need a third-party egg and you also need to harvest an egg from the original woman and then you need to do whatever laboratory procedures are involved.)

But remember that any child that results here will have a genetic link to the woman who provides the mitochondrial DNA.   If genetic linkage is important than this one should be important as well, and so that leaves people using this technology to figure out how to give meaning to this additional genetic link.

While that’s an interesting prospect, I am drawn to the question I raised yesterday:  This research is fueled by and dependent on people’s desires for a genetically related child.   If more people were more willing to accept a genetically unrelated child, the demand for this sort of technology would weaken.   If genetics were not seen as so important, the demand might actually collapse.

Would that be a bad thing?  It seems to me that lots of research relevant to ART holds a range of benefits.  So, for instance, the ability to understand the genetic origins of various disabilities has potentially very wide use.  But for the moment at least, I don’t see that broad potential for this research.

This leads me to some questions:   For those who place great value on genetic linkage, the research should be important as it allows people to achieve that great good–the genetically linked child.   Thus, I wonder if (philosophically speaking) those people do in fact support the research.    And for those who do not place great value on genetic linkage (and that includes me), shouldn’t we question the resources devoted to this sort of research?

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27 responses to “Update on Three-Parent IVF

  1. I think it is a disaster waiting to happen. There should be limits and this crosses the line and reminds me of the evils of eugenics and we never ever want to go there again.

    Whatever happened to just accepting you would not have kids?

    • Aren’t technologies which enable people to have children with their own DNA the opposite of eugenics?

      The idea that infertile people should just accept they can’t have kids seems to be a lot more popular among people who can have kids or don’t want them, than among people who do want them but can’t.

      • what are you talking about? there are many, many single childless women who choose not to have children via donor sperm.

      • Fair point, I think. ICSI, particularly, may be the opposite of eugenics and that’s one reason why people worry about it.

        You may think this splitting hairs, but I am not so much saying that individuals who are infertile should just suck it up as I am saying that we should try to create social conditions where not being able to have a genetic offspring isn’t a big deal. This, then, might lead to it being less of an issue to people, which I think might be a good thing.

    • Or at least accepting that you wouldn’t have kids that were genetically related to you? I suppose one way of looking at what has happend to that is that now we have the capacity to offer a cure, at least if you can pay for it. And so we do.

      But that said, I’m not sure I see what the disaster waiting to happen is, nor do I see this as a particularly problematic instance of eugenics. They’re not going for the perfect designer baby, but rather the likely to be healthy baby. Can you elaborate?

      • perhaps the disaster is that much like other forms of ART like surrogacy, its going to take the social paradigms a long while to catch up with the new biological reality. Really we are in no way ready for this socially. Psychologically and culturally we still haven’t caught up with surrogacy.

        • I agree that we haven’t caught up with surrogacy but I wonder if this one needs to be so difficult. If you aren’t totally fixated on DNA then I think the contribution of mitochondria is relatively modest and need not require a major assessment of who gets counted as a parent. It’s only because of the small bit of DNA that will be contributed that this might be confusing–at least that’s my initial thinking on this.

  2. So you have convinced the masses that raising someone else’s offspring is just as good as raising your own offspring. How do you propose to get the offspring to believe that? You have not taken into consideration that if a person intends to bring a new child into the world its way better to bring one in that can know all his relatives than one that can’t.

    Children should not be produced for sale out of their own families and into the arms of paying customers. Its dandy that people can give up the dream of raising their own offspring and be willing to raise someone else’s offspring but its not possible to know how the offspring is going to feel about that. If someone else’s offspring is already being neglected and needs a home then fine adopt them but don’t go asking someone to create neglected offspring for your benefit hoping that child won’t grow up to feel slighted and com-modified. If the genetic link is irrelevant to you then adopt an existing child don’t fkg have another person make you a baby if you are not willing to have that person play the roll of parent right along side you. You’ve got to include the feelings of the person created into your equation.

    • First off, I don’t imagine that I’ve persuaded anyone of anything, really. I’d be happy to hear I’m wrong about that, though.

      But let’s imagine I did. Then people would accept that the genetic link isn’t all that important. And kids would grow up in that environment and they’d think it, too. And so it wouldn’t be a terribly big deal if you were adopted or conceived via third party gametes or conceived via your own parents gametes. You would know, mind you, because people would recognize the value of openness and honesty and there wouldn’t be shame or stigma attached to it anyway. (If I’m persuading people of things, I might was well have the world just as I want it, right?)

      Perhaps you’d still be curious about genetic linkages and so you’d have access to information about that as you grew up. Perhaps it would still be important for medical purposes and we could cover that ground, too. But the critical thing for me here is that just as it didn’t have so much social meaning for adults, it wouldn’t have so much social meaning for kids, either. Again, I don’t think that that kids just automatically care about genetic connections. Like the rest of us, they learn about what’s important from their families and from the larger cultures. So when I got to change the way people think above, it changes how children think, too.

      • So in Julie’s utopia people do know their genetic relatives and there is nothing concealed from them. Fine I choose your utopia over the current reality. At least in your world children don’t loose a family in order to gain another one. I’m in.

  3. I get the sense that humanity will be split into two species eventually if this takes off
    well this kind of stuff has been going on since time immemorial, since before we and the chimps split off from the same ancestry line, but it is still frightening to think about

    • This seems pretty unlikely to me. The contributions of mtDNA are both minor and (as long as it’s not flawed) hard to percieve, so I don’t think we’ll be sorting people by whether the mtDNA and the DNA come from the same person.

  4. Julie asked: But that said, I’m not sure I see what the disaster waiting to happen is, nor do I see this as a particularly problematic instance of eugenics. They’re not going for the perfect designer baby, but rather the likely to be healthy baby. Can you elaborate?

    What are the genetic implications of mixing two different peoples sets of genes – yes I know one is mtdna vs dna but they have not even figured out exactly how one persons total dna works when it comes to this gene turning on this gene or turning off this gene and that is just the basic level I can understand let alone all the really technical stuff. Until they can say they know all of it – then they should not muck with combining different parts from differnt people. I do understand they are doing it to omit a hereditary disease but they don’t know what the mtdna of one will do when mixed with the dna of another. We are so far away from having those answers it is wrong to start creating humans this way.

    • It seems to me that this is the argument–which I gather the HFEA accepted–that more testing was warranted. And perhaps you are right that more testing is warranted. But this is a little different from saying “it’s eugenics” or from saying that it is a disaster waiting to happen. What I gather is that thus far testing has not revealed much that is problematic.

  5. ml66uk – you don’t know me so please don’t assume who I am, what I want or don’t want, what I can or can’t do.

  6. I wasn’t assuming anything, but I stand by what I said. The idea of “just accepting you would not have kids” never seems to have been that popular even before the advent of medical treatments for infertility. There are stories of adoption in the Bible.

    Regardless of your personal situation, most people, especially those who want children, but are infertile themselves, seem to find it acceptable for infertile couples to use ART to help them have children. Since donor gametes, IVF, and ICSI are commonplace (and paid for by some governments), then unless there are safety issues, I don’t see why using donor mtDNA would be a problem.

    If by some freak of nature, it turned out that I had a stranger’s mtDNA, I really can’t see how it make any difference to me. The nuclear DNA is far more important.

    • But yet what a surprising blow-back you get from those same infertile couples who use ART are completely fine with their kids “never knowing where they came from”. Good for the goose but not for the gander…or in other words “my wants matter” yours not so much.

      It is very easy to assume how you would feel knowing you will never be in that position. Very much like wearing a blind-fold for a day and saying you know what it would be like being blind…the problem comes in that you know at the end of the day you can see therefore only providing you with the merest view of what it is like to know you will never see again.

      • I’m not sure I understand the argument you are making here. It is true that we are limited in our ability to understand experiences and feelings of others–and I’d say that across the board. It seems to me that if we haven’t had an experience, the best we can do is listen carefully to those who have had it and perhaps try to stretch our capacity for empathy. Indeed, even if we have had a particular experience it’s probably wise to do this since it seems human reactions vary widely and for many different reasons. This is why I am wary of broad generalizations (though I do make them from time to time) and also why I am sometimes wary of basing too much on individual anecdotes. It’s not that I think we cannot learn from them, but what we learn may not be universally true.

        But all that said, I’m not sure how it has bearing here. Is the idea that we cannot be sure how kids born of this process might feel? That’s true, I suppose, but it’s always true that we don’t know how kids are going to feel. And I think to a large extent (and maybe this is where we differ?) kids will take important cues from the adults around them. If everyone thinks it’s not a big deal, then I doubt it will be a big deal. Conversely if everyone makes it into a big deal, I’m pretty confident it will be a big deal.

        This goes back to something I wrote here yesterday–I don’t deny that the cchildren will have feelings, but I don’t think the feelings are naturally occuring and beyond our control–like the tides, say.

    • I just realized I misunderstood what you meant. There’s an ambiguity (or at least, a potential ambiguity) in saying “have kids.” It might mean (and now I think you meant it to mean) “raise kids.” But it might also mean (and I understood it this way) “create genetically related offspring.” Thus, I suspect my comments are off point. Sorry about that.

      I agree that the mtDNA probably isn’t terribly important–unless, of course, you care deeply about DNA as a marker of family. Then this is a bit confusing.

  7. Got a question! This matters to me but it won’t matter to you Julie but its a technicality that I’d like to know the answer to: Who are the resulting children related to? Like given a maternity test will it appear that the child is the offspring of both women, only one woman to a lesser degree? My gut tells me that the child still ends up being the genetic offspring of only one woman and one man but that the donated serves as a vehicle for vessel for the other woman to reproduce. If that were the case then for the first time, I would see donors as donating eggs rather than children because they would not have to agree to the production of their own offspring, nor would they have to agree to not be involved in their offspring’s lives because the process would not result in the birth of the donors genetically related offspring. They really would just be helping other people have their own children vs. giving them theirs.

    If that were the case then I imagine the cost of egg donation would plummitt – nobody would care what the donors looked like or what their SAT scores were. Race would not matter I don’t even know that the donor’s blood type would have to match, right? If the child does not end up related to the donor in any way. It sounds like the donor’s mtdna is donated to the woman that does not have good mtdna – like say the same as if the lady had a bad kidney. The dna of the new good kidney stays just in the kidney and makes the body operate as it should. You get pregnant with that donated kidney in your body the kid will be related to you and not the kidney donor. Maybe donating good mtdna makes the womans body work right and she gets pregnant and the kid is related to her not the donor. The dna is not used to make the embryo its used to fix the bad egg right?

    • I’m not an expert here, but as I understand it, if you carefully trace the DNA you will find that the mitochondrial DNA in the embryo links back to one woman and the nuclear DNA links back to the other. Thus, I suppose you could say the embryo is related to both women–it depends, of course, on what you mean by “related to.” In general, as I understand it, the mitochondrial DNA is a tiny contribution relative to the nuclear DNA. Almost all of what we consider inherited characteristics (hair color, body type, and whatever else) is tracable to the nuclear DNA. But there is mitochondrial DNA and it does matter (that’s why you cannot use the original woman’s eggs, after all.) This is why they talk about the child having three genetic parents.

      It is an interesting point you make. The child would not share any of the characteristics from the egg donor’s nuclear DNA because that gets removed. I do think that the mtDNA ends up as a part of the child’s genetic makeup, but maybe I’m wrong about that. In that sense it isn’t quite like an organ donation. It’s just that for most of us, mtDNA doesn’t have any meaning because it doesn’t manifest itself, I think.

      I am really a little out of my depth here, though, and am surely willing to be corrected by someone with greater understanding.

      • I remember when Lacy Peterson’s body was found or they thought it was found they did a mtdna test to establish that the body was in fact Lacy’s. So in that case the MTDNA woman is the child’s mother so wow, this would complicate things. The child really would have inherited traits from 2 actual mothers good grief.

  8. would the child inherit this trait from the mother and also have to go through this process herself when she wanted to have a child?

    • I think the child would have the mtDNA of the donor and would pass that along to her children if she is a girl. If the child is a boy, then I think the mtDNA doesn’t go anywhere. It’s only inherited through the female line.

  9. I think the child would get the mtDNA from the other woman, so would not need the same process to have grandchildren. If it’s a boy, then his mtDNA wouldn’t be passed on anyway.

  10. Julie said: “It seems to me that this is the argument–which I gather the HFEA accepted–that more testing was warranted. And perhaps you are right that more testing is warranted. But this is a little different from saying “it’s eugenics” or from saying that it is a disaster waiting to happen. What I gather is that thus far testing has not revealed much that is problematic.”

    Julie, this process is eugenics which would be considered positive eugenics vs the negative eugenic practices such as forced sterilization etc. http://www.medterms.com/script/main/art.asp?articlekey=3335

    Testing may not have shown concerns but testing only shows viability unless they have produced human beings in the lab. All I am saying right now just because they can do it doesn’t mean they should. They don’t have enough knowledge of how genes work and interact and what really goes on.

    With the take off at the speed of light of ART to the masses unless there are some real controls it does have the risk of being a disaster. What happens in 50 years when suddenly they figure out that the mtdna has changed how the dna operates and now they are suffering from diseases with high levels of morbidity? If the industry was highly regulated that would be one thing – as it is here in the US – its the wild west and those with the money to lobby will do their best to not have it controlled.

    Even with the controls in pharma you find out years after release of a new drug whether or not it is really beneficial or downright harmful. The IVF/ART industry has the smallest fraction of the number of rules, oversight and ethics regulating compared to pharma and these guys are creating people.

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