Feb 26 2016

Mitochondrial Replacement Therapies

mitochondriaAnother innovative medical technology is on the brink of being applied to actual patients, and it is spawning the typical discussion about the ethics of altering human biology. I think this will likely take the usual course.

The technology is mitochondrial replacement therapies (MRTs). Mitochondria are organelles inside every cell. They are the power plants of cells, burning fuel with oxygen to create ATP, which are molecules that provide energy for all the processes of life.

Interestingly, mitochondria probably derived from independent cells that evolved a symbiotic relationship with eukaryotic cells. They are like bacteria living inside each cell with a specialized function of making ATP.

Mitochondria still retain some of their own DNA, which is partly how we know they were once independent organisms. Mitochondria contain 17,000 base pairs and just 37 genes (compared to 20,000 genes in human nuclear DNA). Over millions of years of evolution they have also outsourced some of their DNA to the nuclear DNA of cells, but also still retain some of their own DNA. Not only does this mitochondrial DNA affect the functioning of the mitochondria itself, it has implications for overall cell function through its interaction with nuclear DNA.

There is a class of diseases known as mitochondrial disorders that result from harmful mutations of the mitochondrial DNA. These diseases can be quite devastating, which is not surprising given how critical mitochondrial function is to every cell.

Also, mitochondria are almost exclusively inherited from the mother, because eggs are large cells that contain mitochondria and other organelles, while sperm are stripped down DNA delivery systems that contain few or no mitochondria.

This situation creates an opportunity to prevent the inheritance of harmful mitochondrial mutations, and that is where MRTs comes in. Essentially these techniques involve taking mitochondria from a healthy donor and combining it with the nuclear DNA of the mother during in-vitro fertilization. This technique results in so-called “three parent babies.”

MRTs were recently approved in the UK, and the US is also considering approving human trials of MRTs. Thus begins the ethical discussions.

One concern is safety. This is, of course, a perfectly reasonable concern for any new medical technology. One interesting specific concern is mitochondrial-nuclear mismatch. Mitochondrial DNA and nuclear DNA evolve together, and they interact affecting the overall health of the cell. Some researchers have found that when certain populations of the same species are bred together the offspring are unhealthy due to a mismatch between their nuclear and mitochondrial DNA.

The question is – how much does this mismatch affect apply to humans? Will the nuclear DNA from one woman always play nice with the mitochondrial DNA of another when combined in the same cell? Not all scientists are worried this will be a problem in humans. Others feel we should match donors and recipients so that they have the same basic mitochondrial type (called a haplotype).

In any case, research will need to confirm the safety of MRTs in humans. That I consider to be completely standard.

Others have raised ethical concerns regarding some specific techniques that require destroying an embryo in the process. However, this is a generic concern for IVF, which inevitably involves destroying unused or less healthy embryos. I don’t see this as an eventual stumbling block.

Another concern is that changes to mitochondrial DNA can affect the germ line, meaning that they can be perpetuated in offspring and therefore change the genetics of future human populations. This is only a concern if the technique used damages or alters the donor mitochondrial DNA. It seems research will quell this concern. Meanwhile some have called for early research to produce only male children, who will not perpetuate the mitochondrial DNA.

The final category of ethical concerns is over the psychological and social impact of having three parents. While I would not ignore these concerns, they also don’t worry me. If history is any guide these kinds of concerns rapidly fade once the benefits of a new technology are fully realized.

I think that the history of IVF is a reliable guide to how this generally plays out. People are uncomfortable with a new medical technology that challenges our quaint notions of what is “natural” and about the “sanctity” of the human body. They will complain about putting animal parts in humans, putting machine parts in humans, altering anatomy, and seem especially squishy about altering genetics.

From my point of view these reactions all stem from a basic uncomfortableness with the reality that we are just meat machines. We are biological machines that can break down, and can be altered and manipulated without theoretical limit (the only limits are practical and related to our current technology).

People do incrementally become more comfortable with the implications of this undeniable reality when a new medical technique provides tangible benefits. When parents can have children free from mitochondrial disease, the technology will be embraced.

I think this is and will continue to be a general trend. When stem cells start curing loved-ones, everyone will forget that they were ever controversial. No one bats an eye at IVF today, and no one will bat an eye at mitochondrial therapy tomorrow.

18 responses so far

18 thoughts on “Mitochondrial Replacement Therapies”

  1. carbonUnit says:

    Interesting resonance between this post and this recent news item about aging:

    Scientists make significant anti-aging breakthrough

    “Our study shows, for the first time, in human skin that with increasing age there is a specific decrease in the activity of a key metabolic enzyme found in the batteries of the skin cells.

    Techniques were used to measure the activities of the key enzymes within mitochondria that are involved in producing the skin cell’s energy, a type of mitochondrial gym or skin physical. This was applied to cells derived from the upper (epidermis) and lower (dermis) levels of skin.

    It was found that complex II activity significantly declined with age, per unit of mitochondria, in the cells derived from the lower rather than the upper levels, an observation not previously reported for human skin.

    Initially, I would expect that this is something that would be treated on adults, not as an IVF thing. In the long term it could be come a “designer” criteria. I wonder if this is what’s behind those kids that age so fast they look like old people.

    (The whooshing sound you hear is the alt-med crowd preparing to create treatments that claim to be based on this…)

  2. RC says:

    I still think that the majority of the time the phrase “the ethics of human biology” or its ilk are used, it just boils down to religious people getting unspecifically upset that the technology threatens their beliefs.

    There’s nothing unethical about gene therapy, IVF, or altering human biology. There is absolutely nothing unethical about improving the quality of someone’s life, or rescuing them from some horrific disease present in their genetics. There’s nothing intrinsically good about flawed genes.

    We need to stop being slaves to uncomfortable, regressive religious people, and the naturalistic fallacy.

  3. BenE says:

    To be fair, about a third of the US population still has ethical concerns with IVF (Pew Research, 2013). You’re right about the cause. Some people believe humans have souls and thus IVF is murder. This is a particularly hard delusion to dislodge. It’s why opinion of abortion has been so slow to change and is still a major political issue.

  4. RC says:

    33 Percent of Parents of children under the age of 18 surveyed in the US in 2014 (Harris) thought that vaccines caused Autism, and shouldn’t be administered.

    I don’t think we should use Polling data to decide what’s ethical.

  5. Andreas says:

    I do think that valid ethical concerns into play where the freedom or dignity of other individuals are being infringed for the benefit of some people (as in the movie The Island). This doesn’t seem to be the case here though.


  6. mumadadd says:


    “I still think that the majority of the time the phrase “the ethics of human biology” or its ilk are used, it just boils down to religious people getting unspecifically upset that the technology threatens their beliefs.”

    I agree, but worse can be found here:


  7. BillyJoe7 says:


    The man with a deaf ear and a muscle disorder that makes him limp would not have wanted to have these imperfections corrected becuase those imperfections are part of who he is. Does he not understand that if those imperfections were prevented he would then be a man without deaf ear and a limp? And what about those born totally deaf or totally blind or with cerebral palsy committing them to life in a chair? Do we not treat these people because then they would be different people. Do we not treat them because then we are descriminating against those who are disabled?

    Religion causes people to talk absolute nonsense sometimes.

  8. BillyJoe7 says:

    …and a collection of fifteen cells is a child!
    Have you ever heard anything more ridiculous?

  9. mumadadd says:


    Who are we norms to tell people with Huntington’s that that they’d be better off without their fatal degenerative disorder? Essentially if you correct this disorder you are killing the person who could have been and substituting somebody who fits your privileged preconception of “better off”. FFS….

  10. BillyJoe7 says:

    I know someone with huntingtons and she would give everything not to have this progressively disabling disease. It’s soul destroying. There absolutely nothing character building about having this disease. It is just completely and progressively demoralising. If there was a prenatal test and cure for this disease it would unethical not to use it, even against the wishes of a parent. Yes she would have been a different person from the one she is now. She would be a person without huntingtons disease and so much the better for it. Let this man tell us how character building his deaf ear and limp have been and made him the person he is today. To me he is just an idiot with nothing to say to a person with huntingtons.

  11. BillyJoe7 says:

    …sorry, I have no time for someone who talks absolute bv//$h!+ built on an evidence-free dogmatic religious (or political) belief.

  12. Damlowet says:

    I have come to know a little about some of the regulars here that contribute good and positive information around Steve’s core articles, I appreciate and respect most of their points of view. But this comments section has gone close to a nerve with me, so I feel I must respond.

    First things first, as Skeptic’s we should be looking a little deeper than our own base level understanding of how ‘grey’ this issue can be, and realize that although potentially polarizing, there is a good chance that if someone disagrees with your point of view, you are missing what they are intending to get across.

    I agree with you mumadadd, I hate it when people place appon me and my family what is best for us as if we are less than anyone else who needs to be corrected against our will, and that having a child without a special need is something which is ‘normal’ and must be pursued at all cost.

    I think people should be given all the facts about whatever the disorder is before anyone is compelled by social pressure to abort/test/modify/change, or even try to love their child unconditionally.

    For those of you who want ‘typical’ children, what happens when you crash your car on the way home with your new baby, and they end up a cripple? Do you terminate them then?


  13. mumadadd says:


    I was being sarcastic, and I think BJ7 was aware of that and actually referring to one of the people in the video I linked to, which is what my comment was also in reference to.

    “For those of you who want ‘typical’ children, what happens when you crash your car on the way home with your new baby, and they end up a cripple? Do you terminate them then?”

    Nobody’s talking about termination, but about fixing genetic disorders so that individuals don’t have to suffer them. I feel pretty sure that I would love my child whether disabled, or with Huntington’s, but if the options were available to fix these problems (and they are problems) and I didn’t take it, what would I tell my child? I can’t imagine any ‘typical’ person feeling cheated when they are told that they would have had a disability, or a fatal neurodegenerative condition, had some procedure not been carried out before they were even a foetus.

    None of this is to suggest that people with genetic disorders or disabilities are somehow of less worth than those without.

  14. mumadadd says:

    Yep — fourteen and a half minutes in, there is a guy talking about his “deaf ear and limp”, and how it was character building. I think it’s the Catholic who suggests that if these problems are fixed before birth, you’ve essentially removed from existence the person who would have been.

  15. BillyJoe7 says:

    Damien, a more apt analogy would be doing all you can so that you don’t have the crash that results in your child becoming disabled. Similarly you would do all you can to prevent your child being born disabled. None of this means that you are decriminating against disabled children. None of this means that you will reject your child if these preventative measures fail.

  16. Damlowet says:

    Sorry guys, I have done it again! An early morning read has lead me to miss critical nuanced points of the conversation. My bad.

    So, I have re-read and watched the vid.

    I don’t have an issue with any of the research that is being done on the pre 2 week lumps of cells. ( I used to hold the view that life starts at conception, but that has been pushed back to when ‘we’ have a brain,heart and nervous system), but I still have issue with people choosing abortion after this stage for no other reason than it ‘feels’ unethical to me.

    If we can (through this tech) fix issues pre birth such as hearing issues, sight issues and other quality of life issues, I tentatively think there shouldn’t be a drama with it.

    Within the same ballpark, but slightly OT, where do you guys sit on screening for something like Autism or Down’s Syndrome?

    As I have a vested interest directly in this question, I would like to gauge how far from center I sit ethically.


  17. mumadadd says:


    “I used to hold the view that life starts at conception, but that has been pushed back to when ‘we’ have a brain,heart and nervous system”

    Aside from biology, when trying to determine whether an unborn child is yet a ‘person’, or what rights should be afforded to them, I would also consider what kind of psychological existence they have; so if you have a braindead newborn vs a 6 month old foetus that can dream, I’d afford more rights to the foetus. It’s really tricky, if not impossible, to nail down a point at which an unborn child has reached a sufficient point of ‘personhood’ for their right to life to trump the mother’s right to biological self-determination, but I think abortion law (in the UK — CBA to check everywhere) does a reasonable job of tracking our evolving scientific understanding and balancing the respective rights of the mother and offspring: up to 24 weeks is elective, though you will encounter reluctance after 16 weeks; after 24 weeks then some other specific criteria have to be met, such as danger to the mother’s life.

    “Within the same ballpark, but slightly OT, where do you guys sit on screening for something like Autism or Down’s Syndrome?”

    I think I understand what you’re asking (but apologies if I’m going off on an unnecessary tangent) — what about screening for conditions for which there is no fix, and termination may be considered as an option? I think it’s up to the parents to make an informed choice, so all available relevant information should be considered. Everyone is entitled to make their own choice as to what they do based on this information; e.g. it would be helpful to know if your child will have any special care requirements, or maybe some adaptations need to be carried out to your property, maybe you need to find some amount of money from somewhere to pay for all this, or maybe you learn about the prognosis for your child and decide that you aren’t willing to put yourself through that. These decisions should be made on a case-by-case basis and balanced with the rights of the unborn child, with greater consideration to the rights of the child after a certain fuzzy point in the pregnancy.

    Surprisingly, I think I’m more or less describing what does happen a lot of the time, and the intent of the law on these issues.

    PS: I don’t think there is a prenatal test for autism as yet.

  18. BillyJoe7 says:


    My short reply is that is that a new life begins at conception. I think that is undeniable. But the important question is when we consider this new life to be a person. An absolute requirement for personhood is consciousness, which is considered to begin at about 24 weeks and pain perception begins at about 30 weeks. Most abortions are carried out at 8-12 weeks so pain and personhood are not even considerations.

    The decision to terminate a Downs Syndrome foetus should be that of the mother in consultation with the father and the attending physician. She is the person who has to carry to term and, together with the father, raise the child.

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