And Then There’s Mitochondrial DNA….

I’ve written in the past about technologies that have been or are being developed that would allow IVF using nuclear DNA from one woman and mitochondrial DNA from another.   The idea here would be to avoid certain diseases transmitted via the mitochondrial DNA.  A woman whose mitochondrial DNA carried those traits could have the nuclear DNA from her egg transferred to a stripped-out egg provided by a different woman who did not carry those traits.   This egg–now composed of DNA from two different women–could then be fertilzed for use in IVF.

There’s been a lot of discussion in the UK of both the safety and the ethics of using mitochondrial DNA replacement.  The HFEA (the UK agency that regulates all things ART–which I thought had been defunded but obviously still exists) has been seeking consultation with various communities for some time.   And this consultation continues, as this post from Olivia’s View makes clear. 

There are several things to think about in connection with this.  First, there are the obvious concerns over whether the technique is safe (which it seems to be) and whether it is ethical (I am not troubled by it myself, but I know others will disagree.)

Second, perhaps because I’ve written recently on the expanding egg market made possible by reliable egg-freezing technology, I see now that this might be another (albeit small) outlet for the egg market.   After all, in order to do this you need a third-party egg from which you will strip the nucleus.   Given that the mitochondrial DNA ultimately contributes only a little bit to the child who may result from that process, many characteristics of the egg-provider won’t matter.   But still, you need an egg and eggs have not always been easy to get.   The rise of egg banks will change that.   (I suspect this is a small outlet for the egg market because this technique may not be widely used.  I don’t actually recall how common the occurence of flawed mitochondrial DNA is.)

Finally,  I’m struck by the Olivia’s View note that the HFEA is anxious to take into account the view of the DC Network.   This leads me to think about whether a child conceived via this new technology would consider herself/himself a donor-conceived child.   Of course, the real answer to this is probably something like “some might while some might not”  but even with such a wishy-washy answer, thinking about the question is interesting.

I think, for instance, that some–maybe many–people who understand the idea of a genetic connection between gamete provider and child might not know much about mitochondrial DNA.    It certainly doesn’t have the same place in the public discussions of DNA testing and “real” parents.   If you focus on people who ascribe great importance to genetic linkage, what will they say about the mitochondrial DNA link?    Is it equally important or less so?

Of course, if it is important, this could lead you to say that splitting the genetic connection between the two women is immoral and we ought not to use this technology.  But I don’t know if that is the only conclusion.   Could you instead include that just as it is important for a child to know/have a relationship with a gamete provider, so it is important for a child to know/have a relationship with their mitochondrial DNA provider?

In general, I assume that women who use this technique will be using their own eggs.   After all, if you are using eggs from a third party, why would you use eggs with problematic mitochondrial DNA?   So the women using this technique will have the more substantial genetic connection–the one determined via nuclear DNA–to the child.   What counselling should they receive about telling the child about the mitochondrial DNA?

I’m trying to imagine the parent/child conversation about this.  I can see how a conversation about using third-party gametes generally might go but it seems to me that the mitochondrial DNA conversation is a more technically complicated one that might need to wait until a child is older if you’re going to get even general comprehension.  But perhaps I’m wrong about this?   Maybe there are ways to explain?

All in all I’m just beginning to grapple with the issues that surround the question of how those conceived with this technology might be like/not like donor conceived children.   Unsurprisingly, there’s a lot to consider.

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20 responses to “And Then There’s Mitochondrial DNA….

  1. Just to let you know Julie that the UK Department of Health is currently running a consultation on the future of the HFEA. It seems likely, although not certain, that some functions will be devolved to other organisations, although probably not until 2015. DC Network, and many others, are concerned about the role of the HFEA in holding information about donors, recipients and children conceived via donated gametes and how access to that information will be possible, including intermediary services for donor conception families. I’ll be writing about this when DC Network have agreed their response to the consultation.
    Your speculation about the parent/child conversation in the case of mitochondrial replacement is interesting. For very young children how about something along the lines of, ‘Mummy’s (or Mommy in the US) eggs needed some help from another woman in order to make a healthy baby, so the doctor found a kind lady who was able to give part of her egg to help make you’. More explanation would of course be needed as a child grew and asked more questions, but, as with conventional gamete donation, better to start earlier than later with telling.

    • Thanks for supplying more details. It’s interesting to me that the process seems to be far more open and deliberate in the UK. Perhaps that is because there IS a regulatory body there–the HFEA. Though the FDA may do some minimal regulation here, there’s really nothing like the HFEA.

      One thing that is interesting to me in thinking about these parent/child conversations: The scenario you describe is surely one possibility–a starting point. But all of these conversations require that the child have some grasp of the basics of human reproduction. I don’t mean anything terribly detailed, necessarily, but something beyond “the stork brings babies.”

      The reason I note that is that I think in many households (at least here in the US) discussion of human reproduction is often lacking. I’m not sure what to say beyond noting that. I suppose it means that, at least ideally, families using some of these ART techniques will set themselve apart not only by having these specific conversations, but even by opening up the topic of reproduction.

  2. If positive maternity and paternity dna tests were required as a prerequisite to state certification of birth records it would be obvious who was and was not the offspring of the people claiming to be their parents. Maternity tests are mitochondrial dna tests.
    If a woman claiming to be the mother of a person presented a failed maternity test, she could dispute the results with an autosomal dna test showing shared cm in the neighborhood of 3380cm but then should have to take second billing and share the line for mother on the certificate with the woman with the positive maternity test.
    What is at stake is accurate health records for the person who is the subject of false claim to parentage.
    A truly accurate health record would indicate which of the two women delivered that person; if neither, the name of the unrelated carrier should be entered as a third, but unrelated, party on the birth record. The carriers health can impact the persons health while in utero but is not that person’s biological mother. The person is not related to her or her relatives and should not have the right to access to her birth, marriage and death records or her family member’s birth, marriage and death records the same as they have a legal right to their actual mother’s records and her family’s records because the carrier and her relatives are not significant to the health of the person named on the certificate.

    • I’m confused about the details here and I’m not sure I understand what you say at the beginning. I’m not sure I’ve heard much about maternity tests, but you’re saying that what they test if the 1% mitochondrial DNA and not the 99% nuclear DNA? If this is so is there some technology related reason? I guess I always assumed (but without any basis) that if they did DNA testing to establish the relationship between a woman and a child they’d be looking for the nuclear DNA. You’re suggesting not, right? I didn’t know that. Can you point me somewhere I can read more?

      In any event, if we were to go down this road the social and legal meanings we ought to ascribe to the two (mitochondrial DNA and nuclear DNA) or possibly three (pregnant/birh) relationships would have to be determined. I think I’d agree that a complete medical record would include all the information. And while I can imagine a world in which we’d say all three women are legal parents (or ought to be social parents), it’s not what I’d expect to happen. And I have a hard time imagining that as a general matter, people would want to assign legal preference to the mitochondrial DNA provider over the nuclear DNA provider. (This sets aside the whole question of what to make of the pregnancy/birth relationship.)

      • Sure the FTDNA website is the one that all the donor offspring I help belong to and they got me a membership and boy am I learning a bunch. MDna is the maternal test
        Their nuclear test is what they call the FTDNA test and that you get matches based on shared genes on either side. then there is the paternity test too as you’d expect.

        http://www.familytreedna.com/

        you can poke around but I guess mitochondria is the unique thing that the mother brings to the table in terms of cell reproduction. Like when they did the maternity test to prove the body was that of laci peterson they tested the mother. I guess its less genes but it’s very specifically your maternal ancestors maternal biological make up.
        If a woman could not pass a maternity test the way a man can pass a paternity test there is the other nuclear test that would prove you were another source of a persons biology. It is a small amount but its something needed there has to be a mother or there is no kid. I wonder if they could use male genes for the other part of the nuclear dna in the egg or if they could put female genes in the males nuclear dna its all very crazy but there still has to be that one male and one female mother father source to make a person exist. Crazy.

        • Thanks. So I guess it is fair to say that we do not test for genetic maternity the same way we test for genetic paternity? Interesting.

          In this way, the new technology contemplated here separates elements out we have always related to as being inextricably bound. It seems analagous (to me, anyway) to what gestational surrogacy did, since gestational surrogacy forced us to think about genetic connection separately from birth/pregnancy. We’d always had the two together before.

          That said my guess would be that most people would see the nuclear DNA relationship as being more important than (and therefore trumping?) the mitochondrial DNA relationship. There’s something about the 99/1 and also the fact that visibly heritable characteristics are all nuclear DNA characteristics that makes me think this will seem obvious to people. Which might mean they’ll need to switch to that other DNA test, at least in cases where this technique is used.

  3. My parent's donor is my father

    I remember reading something a while ago about a public health concern, involving those children who are conceived with nuclear DNA from one woman and mitochondrial DNA from another, when those adults reproduce themselves and how that would effect/impact their offspring and how that becomes a public concern. I wish I could find that article. If I do I will share it.

    • I’d like to see it myself (and maybe I’ll learn that you found it when I go down the list of comments.) I did find this additional discussion, but it is rather the opposite view from the one you mention. http://www.guardian.co.uk/commentisfree/2012/sep/19/misleading-three-parent-babies-gene-therapy?newsfeed=true

      • My parent's donor is my father

        John Harris, the libertarian “bio-ethicist” from the UK writes:
        “The problem identified by the HFEA as to whether or not resulting children have a right or a need to know the identity of the mitochondria donor is really bizarre.”
        And he goes on to say that it’s true people want to know the identity of their progenators (well, thank you for THAT – but easy to say since “donor” anonymity is now banned in the UK) but ONLY(?) because of non-paternity issues??? Whaaa???
        He writes: “More importantly, access to information about progenitors implies universal paternity testing with all the mischief that this would entail. This is because of the widespread phenomenon known as non-paternity.”

        So therefore the “need to know” of the identity of the mitocondrial dna mother is a non-issue???
        He writes: “Is this a cause for concern? I doubt it, and doubt even more the wisdom of any measures to “correct” this state of affairs. More mischief and anxiety would certainly be caused by recognising a right to know, or indeed a duty to disclose all contributors to a given genome, which will include contributors in even earlier generations, and our ape ancestors”

        Wow that’s condesending. I can’t take this guy seriously. Sounds like he’s more of libertarian/biased/political agenda kind of guy than a “bio-ETHICIST” (emphasis on ethical) What a numskull.

        • Egad. People do have the right to a copy of their parents birth records marriage records death records all of which contain pertinent information about a person’s own health but if a birth record is falsified the certificates you have a right to are worthless for health purposes. Unless I’m mistaken the CDC collects only original birth records because it uses that information for medical research purposes related to the study if inherited diseases and they have no use for the ratified certificates that are created when people are adopted. If we think there is no longer a point to keeping track of the health of the countries citizens and we’ve done all we can do with studying birth defects and what not, then lets stop funding the cdc and let the chips fall where they will. Our birth certificates are becomming so mired in inaccuracy as to undermine the whole operation. To look at the CDC’s birth stats it looks like women over 40 have no fertility problems and are in fact more fertile than ever before cranking out sets of twins at record pace well into their 50’s and even 60’s.

  4. My parent's donor is my father

    This isn’t the article I was thinking of but it does make mention of this concern (http://www.guardian.co.uk/commentisfree/2012/jun/12/head-to-head-three-parent-babies)

    “Is it safe? No. Each technique involves experimental reproductive cloning techniques and germline genetic engineering (that is, it affects the genes passed on to children) – both of which are highly controversial and potentially dangerous. Cloning by nuclear transfer has so far proved ineffective in humans and unsafe in other mammals with a large number of cloned individuals spontaneously aborting, and others suffering from physical abnormalities or limited lifespans. Also, as the Guardian noted last week, any changes, or unpredicted genetic problems (mutations) will be passed to future generations. In general, the more manipulation needed, the higher the severity and frequency of problems in resulting embryos and fetuses.

    Is it ethical? No. A large number of eggs will be needed, involving risky and invasive “harvesting” for women donors. How many debt-laden students or infertile women will be exploited by the offer of money, or free IVF treatment, in return for their eggs? How many embryos will be destroyed? Then there are the issues of identity confusion for the children, who in effect will have three biological parents. Some mitochondrial diseases are much less serious than others. Once we have judged some affected babies not worthy of being conceived, where do we draw the line?

    This debate is not being handled responsibly. The research scientists involved have financial and research-based vested interests, and getting the regulatory changes and research grants to continue and extend their work is dependent on them being able to sell their case to funders, the public and decision-makers. Hence their desire for headlines and human-interest stories that are often selective about the facts they present.”

  5. right! I mean how did we ever even get to the point where we thought “hey lets freeze some sperm and see what happens!” Like who gave the OK for that? That was major human experimentation was it not? Manually placing fresh sperm and egg together is not a real mental leap from the standard process but when your talking about a tissue donation that does not aid the recipient body in its own self sustaining function but rather actually ends up reproducing the body of the donor female and male and then also reproduces the third person the recipient female its very much taking a chance with someone else’s life. Gambling with other people’s chips is never never ethical. It does not matter how much we stand to gain if someone else is the one that might loose. If all we loose by not doing it is not getting what we want then tough titties for us. Putting a recently-dead guys lung into a nearly dead person’s body does not gamble with the just dead fellows life. The risk and experimentation is born by the guy who might live and it has to be his choice to do the experiment or not. Making a new person who might be physically or mentally or emotionally or legally compromised (freedom and civil liberty and access to information) is wrong on all those levels. Why? So that some broad can live out her childhood dream of raising a baby with her sweetheart? Why would we allow that? Money. The economy. Money money money. Money money.

    • Perhaps I’m less cynical than you but I don’t think it’s just about money. Some people’s empathy for those who can’t have kids is very strong, and you can’t dismiss the importance of someone’s ‘childhood dream of raising a baby with their sweetheart’ – it has a very strong emotional appeal.

      It seems to me this issue should appeal to you because at its core it’s about whether the biological parents – of whatever proportion or percentage – are important or not. If nobody thought it was an issue, we wouldn’t even be discussing it.

      • Your way less cynical than me Kris, no question about that. You have educated me to understand that labs and donors are not compensated in your country the way they are in the rest of the world. Your country is the exception – elsewhere in the world human tissue, reproductive and otherwise is a heavy hitter in the global economy .

        “It seems to me this issue should appeal to you because at its core it’s about whether the biological parents – of whatever proportion or percentage – are important or not. nobody thought it was an issue, we wouldn’t even be discussing it.”

        Yeah but it is no different than regular donor conception where the child looses half their bio family – ok so now they loose a third of their bio family. And they are loosing the only woman who can pass the standard maternity test. They are loosing their maternal relatives.

        I guess you get into a situation where some people would have their maternal and paternal line (mother and father) like normal and then I guess you’d have your additional female autosomal relatives. Maternal and Paternal Grandparents plus your Female Autosomal Grandparents. Complicated. I accept that its happening I just want people to be treated fairly and have the same rights as others when this is done to them.

        • Even though there’s obviously a lot of money in ART in the US and doubtless some are in it primarily for that reason, I have no doubt that there are people–many people–who work in the field who are motivated primarily by a desire to help others. Remember that not everyone shares your view about the appropriateness of using third-party gametes. And not everyone who disagrees with you does so for reasons of greed. While I won’t deny the influence money has, I also want to acknowledge the genuine motives that are at work in many people.

  6. I just would not go there about not being worthy of being conceived. We can’t worry about the lost lives of people who don’t exist because the law made people choose not to procreate. People decide not to reproduce for millions of reasons and we can’t have a funeral for every child never conceived. We should however have laws that protect the rights of born individuals to be treated fairly and justly upon their arrival and that means ensuring that we all have a medically accurate identity where the individuals who reproduced to create us are recorded on our birth records as our parents. Prior to birth our cells are not ours they are the cells of the people undertaking the reproductive process. I have to contemplate this more. If a person wants to tamper with their own cells in such a way that produces a mangled baby…well you don’t get arrested for drinking while pregnant and it makes you no less the mother of the resulting child. I suppose I should stick to my line of thinking that people with offspring ought to be obligated to their offspring’s care, so no hiding out if your going to do this all three of you should be permanently on the hook. No hiding out no secret donor agreements. Take responsibility for your reproductive behavior.

  7. I don’t pretend to know what is the solution for the muddled kinship lines that are bound to result from this procedure. And i don’t believe anyone else does either.

    • Agreed. If we go this route–and I’m sure some people some places will–then again we are crossing into new territory. It’s good to try to think it through in advance. To me, the fact that it is unknown territory doesn’t mean that we ought not to go there–but it does mean we ought the think first.

      • And if you think about it and realize that the person you create will loose something that other people have is it just for us to say that what they will loose is of no relevance and there fore they should suck it up and get over it? Or should we suck it up and get over it and only undertake tasks where if someone looses its us and not anyone else. If your about to make a person that has no right to know who their relatives are when its important in order to make informed health decisions then don’t do it. There is a big difference between not knowing who your relatives are due to some unfortunate turn of events like being abandoned and specifically not having the the right to that information when other people do. We are breeding a second class of individuals with fewer rights. Until they have the same legal rights moving forward knowing their freedoms are compromised is unethical.

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