Three Parent Panic

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    Chris Becker (CC / Flickr)

    Parliament is debating whether to allow mitochondrial replacement.

  • It will not help people with mitochondrial disease, but will allow women with defective mitochondria to have children who are related to them.
  • The Church of England claims the issues have not been sufficiently researched or debated.
  • How much risk is acceptable to enable a mother to be genetically related to her child?

A child with three parents is like a joke with two punchlines. Hence: Jesus had three parents and he…

…turned out OK.

…only lived to 30.

The punchline you prefer probably indicates how you feel on the issue of three-parent babies or, to give the medical procedure its proper name, mitochondrial replacement.

Britannia is in a tizzy over mitochondrial replacement

If you don’t live on this drafty little island, you probably don’t know what I’m talking about. Bear with me because it’s bound to come your way soon, probably with as much furore as it’s caused over here. Tomorrow, the House of Commons will vote on whether to change the law to allow embryos to be created by placing the nucleus, containing most of the embryo’s genes, into an egg from a donor other than the genetic parents. The embryo, and the child it would develop into, would contain genetic material from the mother, the father and the egg donor.

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Aff Photography (CC / Flickr)

If Parliament votes to change the law, the UK will be the first country to allow the technique to be used as a fertility treatment. If it is successful, We can expect other countries to carry out a similar review of their legislation.

Human genetics is an emotive subject. The tangle of issues has dominated the news over here for the last week. What reasonable person wouldn’t be concerned about babies born from an experimental procedure? This post is my tuppence worth.

What are mitochondria and why would we want to fiddle with them?

 

A billion and a half years ago, life was much simpler than it is now. I don’t just mean the lack of inflation, political parties and social media. I mean that the most complex cells were little more than a bag of biochemicals. Something dramatic happened the day a small cell took up residence inside another. There was probably a lengthy period of accommodation, as usually happens between a landlord and a new tenant, but ultimately the two cells settled into a symbiosis that has lasted ever since. The larger cell supplied the smaller cell with metabolites that the smaller cell converted into energy. After a few hundred million years of evolution, neither could survive without the other. When cells started clumping together to form plants and animals, they took their symbiosis with them. By then, the smaller cells had ceased to be cells and become mitochondria, a vital part of any plant or animal cell.

SEM_mitochondria

Jay Reimer (CC / Flickr)

There’s a better explanation here. With pictures.

While the mitochondria are fully integrated into the cells of animals like us, they never completely lost the genetic material they carried as free-living cells. We humans are derived from around 30,000 genes, of which 37 are carried by the mitochondria. While we get most of our genes from both parents, our mitochondrial genes come entirely from our mothers. When we are conceived, the sperm enters the egg and carries our father’s genes into the nucleus, but the sperm takes no mitochondria with it.

Evolution tends to come up with arrangements that are over-complicated and accident prone. Supplying our cells with energy from an accidental fusion of two cells a billion and a half years ago is the sort of thing that drives any engineer’s head into their hands.

Inevitably, it goes wrong. Mutations in the mitochondrial genes accumulate until, in one unfortunate generation, they reach the point where they are no longer viable. The result is children who are disabled and often short lived.

Mitochondrial replacement

Rather than give a dry medical description, I’ll leave it to Sharon Barnardi to describe the seven children she lost to mitochondrial defects:

https://www.youtube.com/watch?v=BmUNPPYwSIk

Pronuclear transfer is the transfer of the nucleus, containing the genetic material from the mother and father, into a donor egg. The donor egg contains the donor’s mitochondria, which contain the 37 mitochondrial genes from the donor, hence the term ‘three-parent baby’ so beloved of the media.

Whence lies the rub.

On the one hand, it defective mitochondria are not passed to the child. On the other, the mitochondria that are passed on carry 37 genes that come from a woman who is not the mother.

There are two techniques for mitochondrial replacement. Pronuclear transfer involves fertilising the mother’s egg and then transferring the pronucleus to a donor egg:

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Spindle-Chromosomal Complex Transfer involves transfer of the mother’s chromosomes before fertilisation, and then  introducing the sperm to the donor egg which now contains the mother’s genes:

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The Church of England objects

Objections to the procedure come from a number of sources, most vocally and perhaps least coherently the Church of England. It may seem strange that the church’s opinion carries any weight in a country as secular as the UK, but the CoE holds seats in the House of Lords so it has a voice in any issue coming before Parliament.

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Jack Pease (CC / Flickr)

The CoE’s influence makes it unfortunate that the statement by Brendan McCarthy, the CoE’s adviser on medical ethics, is so confused and self-contradictory. He summarises the CoE’s position in an interview with the BBC.

McCarthy states that ‘changing the human germline represents an ethical watershed’, but goes on to say, ‘we… are not opposed in principle to mitochondrial replacement’. Whether mitochondrial DNA should be characterised as part of the germ line is debatable, but the lack of opposition in principal shows that not even the CoE thinks it matters.

McCarthy goes on to say, ‘the law should not be changed until there has been further scientific study and informed debate’. However, he also says, ‘the Church has participated in the debate at every stage’ and mentions the public consultations held by the Department of Health, the Nuffield Council on Bioethics  and the Human Fertilisation and Embryology Authority. If McCarthy’s view is that something has been lacking from the years of debate and discussion that he has participated in, he should say what it is.

Similarly, he calls for more scientific study. His objections oppose the views of a great many scientists, notably the 40 scientists from around the world who signed an open letter supporting pronuclear transfer. If McCarthy thinks he knows something they don’t, I would like to know what it is. If the CoE’s objection is not on principal, we can infer that there are particular points it wants addressed by research. In that case, McCarthy should be able to tell us what research he would want carried out for the CoE to support mitochondrial replacement. Simply saying ‘more research’ amounts to waving his hands around and hoping we accept his opinion on authority.

In fairness to McCarthy, the Nuffield Council on Bioethics is similarly vague in that it states ‘if these novel techniques are adequately proven to be acceptably safe and effective as treatments, it would be ethical for families to use’ without stating what proof it regards as acceptable.

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ynse (CC / Flickr)

The Catholic church of England and Wales issues a similar statement which covered much of the same ground but with a little less internal contradiction. Unlike the CoE, the Catholic church objects to any destruction of an embryo, which it regards as a human life. Its concern does not extend to the half of embryos are spontaneously aborted without the mother even knowing about it, but I’m in danger of digressing.

The Catholic statement does at least recognise that further research would involve actually trying out the technique, and follows its own logic to far enough to object to that research being carried out.

 

Mitochondrial replacement protects genetic heritage rather than lives

A more detailed objection comes from the secular pressure group, Human Genetics Alert, who are more concerned that pronuclear transfer amounts to genetic engineering of human beings. They go on to suggest alternative paths to motherhood for women with mitochondrial disorders, including egg donation and adoption. HGA do not explain why they regard it as unacceptable to select 37 mitochondrial genes from a donor but are perfectly happy to select all 30,000 genes from the nucleus, but they do point up an issue that has been missing from much of the discussion:

The aim of mitochondrial replacement is not to save lives. It is to allow women with defective mitochondrial genes to pass on their own genes to their children.

As mitochondrial replacement is not a treatment for anyone currently alive, HGA describe it as ‘a social rather than a medical benefit’. This point is key to the ethical decision:

How important is it for women to have children that carry their own genes?

The key question of safety

Which brings us to the safety argument. A person born following mitochondrial replacement will have to live with any complications that arise from the procedure. Healthy cynomalgus macaques have been born following mitochondrial replacement, but there’s simply no way to know whether a human born by the same technique would be as healthy until it is tried.

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Louish Pixel (CC / Flickr)

Risk is relative, and the comparison we need to make is not with a normal, healthy child but with a child with mitochondrial disease. For a woman with defective mitochondria, reproducing the traditional way is far from safe and the evidence available at the moment is that mitochondrial transfer would make that woman’s child more likely to be healthy than simply hoping for the best.

If you’re still with me, you’re probably wondering what my own view is. I hope Parliament vote to approve mitochondrial transfer because legislation should only prevent people from doing something when there are much more compelling arguments than have been advanced against mitochondrial transfer. It should be up to the parents in question to decide whether the continuation of the mother’s gene line is important enough for them to undergo the technique.

For all that, I would not be the first parent to sign up.

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