The pioneering IVF procedure known as mitochondrial donation therapy (MDT) could prevent children from being born with devastating mitochondrial diseases. Madeleine Finlay speaks to Prof Darren Griffin, an expert in genetic diseases and reproduction, about how MDT works, the ethical considerations attached, and what techniques like it could mean for the future of reproduction. Help support our independent journalism at theguardian.com/sciencepod

This week, The Guardian broke the news of a first in the field of fertility science in the UK.

Now the first baby created from 3 genetic parents has been born in the UK.

The breakthrough is aimed at stopping a mother passing on defective genes to a child.

The pioneering technique developed by doctors at the Newcastle Fertility Centre, is known as mitochondrial donation treatment, or MDT.

Mitochondria provide energy to the cell and fuel the body.

So when these are abnormal, a person can be severely affected.

This could be anything from brain damage, muscle wasting, heart failure to blindness.

Conditions can even be fatal within days or even hours of birth.

So this new technique holds a lot of promise for those impacted.

But there are still plenty of unknowns about long-term outcomes, what these changes could mean for subsequent generations, and how the technology could be applied in the future.

From The Guardian, I'm Madeline Finlay and this is Science Weekly.

Darren Griffin, you're a professor of genetics at the University of Kent and you've done lots of research into genetic diseases and reproduction.

So I'm keen to understand how significant this news is that the first baby has been born in the UK with DNA from 3 people.

Yeah, it's worth unpacking it a little bit because it's a technology that we've known about for some time.

So I've been aware of it for about 10 years, but it was being talked about before then.

In many ways, it's a very obvious thing to do.

The technology itself isn't a million miles from the so-called cloning technology, the nuclear transfer.

We were certainly aware from conferences that this treatment was happening.

We were certainly aware that there had been treatment licences and that patients had undergone treatment.

And the UK isn't the first country to create babies using MDT.

In 2016, a US doctor announced the world's first MDT birth.

But in each case, this technique is being used to prevent harmful mutations, abnormal mitochondrial DNA, from being passed from mothers to their children.

So just give me a sense of how this works.

Although the vast majority of our DNA resides in the nucleus, There's a tiny bit that resides in somewhere else, which is a mitochondria, which is sometimes referred to as the power packs of the cell.

Now if that DNA is compromised, if it has a mutation, then we know that it can cause some pretty severe diseases.

So the way that this works is that the patients receive the mitochondrial DNA from a donor but the vast majority is still from the biological parents.

You've got majority DNA from the parents, but you've got this part of the DNA from a third party donor.

It's not a million miles from going into an IVF clinic and having regular treatment.

And at that point, an embryo is then produced from the parents that the vast majority of the DNA is from those parents because it's in the nucleus.

That nucleus is taken out because the mitochondrial DNA might well be affected with this disease.

We take the nucleus out and put it into a donor egg that has healthy mitochondria.

So it's all done under a microscope, under micromanipulation.

When that nucleus is then inserted, it has all the DNA from the parents themselves, all the genetic traits that they would hope to pass on, but this tiny amount that has the healthy mitochondria in it that's not part of the nucleus.

And I know there's an alternative method where the nucleus of the mother's egg is swapped into the donor egg before it's fertilised with the same outcome, parent DNA with the donor mitochondria in an egg that can then be implanted into a womb.

It's quite incredible but is there any other way to prevent a baby from inheriting mutated mitochondria?

Well, 1 could of course undergo prenatal diagnosis, so establish a pregnancy and then ask the question if the child is affected, the child in the womb is affected, whether you undergo a termination.

I'm not aware at the moment of any effective treatment of children that are born with the disease, there are certain things that you possibly could do to mitigate depending on the disease to mitigate the symptoms but they would still always have the disease.

So in terms of ensuring that they're born without it, it is a very very effective treatment in that sense.

Anything else, so if it was some sort of gene editing therapy, you've got to bear in mind that there are lots of mitochondria in the cell where there's only 1 copy of the nuclear DNA, so you would have to try and be able to edit sufficient numbers of mitochondria in that cell.

And that brings a whole set of other ethical questions along with it.

Now I want to get into some of the ethical questions, but first off, you said this was a really effective treatment, but I wonder if there are any risks involved in doing it.

I think the first thing we have to say is that any treatment that has the power to do good also has the power to do harm.

You can take a paracetamol, for instance, for a headache, take too many of them, it could affect your life.

So we always have to balance those things.

The 1 big unknown, of course, is that although the babies are born healthy in 20, 30, 40 years, is there some sort of knock-on effect thereafter?

On the balance of probabilities, we think not, or we think that it would be very minor, but of course we never know for sure until we've followed these children up in 20, 30, 40, 50 years.

And when we consider the alternative that the children will be born with these severe diseases and children will continue to be born, we have to consider what is a lesser of 2 evils and in my personal opinion that should be somewhat of a no-brainer.

Recent research has found that in some cases, the tiny number of abnormal mitochondria that are inevitably carried over from the mother's egg to the donor egg can multiply when the baby is in the womb.

This is called reversion or reversal and it could lead to disease in the child.

According to Dagan-Wells, a professor of reproductive genetics at the University of Oxford who took part in the research, the reason why reversal is seen in the cells of some children but not others isn't fully understood.

As Darren said, now scientists will be monitoring the babies who have been born using this technique to see what happens next.

So Darren, I'd really like to talk through some of the ethical considerations here because it seems like a no-brainer to provide this treatment to somebody who could have a very serious genetic disorder.

So what kind of things were scientists thinking about beforehand?

I think we need to look back at the UK's history in this area.

And of course, when something new comes along, it raises alarm bells, the yuck factor, if you like.

Now, you think back in 1978, the UK was the pioneer of IVF.

In the 1990s, pre-implantation genetic testing.

Then we had the whole thing surrounding savior siblings.

And in each of those cases, the science went alongside some very sensible regulation.

And that's why the HFEA was formed, the Human Fertilization and Embryology Authority.

Now I agree with you, I think that it should be a no-brainer because the alternative is children dying, being born with very severe diseases, having a very, very poor and short quality of life.

That's not to say that it doesn't raise ethical questions.

Of course, when you are considering that there is a tiny bit of someone else's DNA, do they have any legal rights to access to this child?

It's 1 of the things that you just need to consider and perhaps you can deal with through legislation.

The term three-parent IVF has never been 1 that I liked.

The parents are the biological parents in the nuclear DNA and that's it.

And safety is always an issue and my colleagues in Newcastle I know you know 1 of the best groups in the world for doing this and I know that they would do this very very safely.

But when you start rolling this out to many, many clinics across the world, you then have to have a regulatory procedure in place, a training procedure in place, a quality assessment procedure because not every 1 of those embryologists necessarily would be as highly skilled, you know, they might be relatively new to the job, as the people who are at the very top of the game in Newcastle.

Other than that, I think we start getting into arguments of people say, oh well you're messing with the germline and you say well just think about the practicalities of this for the moment this is something that's only passed down the maternal line so as soon as a male appears in that germline then this issue would would go go away you know so while ever there are female to female transition, yes, that DNA would persist.

But the first time a male is born in that line, it would go away.

So, it's always a question of benefit over risk.

And in this case, I really, really encourage people to think about what are the alternatives and to turn the ethical question another way around.

Given that we've got the abilities to do it, is it unethical not to do it in that case?

At the moment, this is being used for, as you've said, very serious diseases, but could it be used for anything else?

Are there other applications that we could see in the pipeline?

We get to the stage of considering what is a genetic disease and this applies to the whole of prenatal genetic testing as well, that when you think that there are diseases, these are not mitochondrial diseases, but diseases such as Duchenne muscular dystrophy, which is highly debilitating, has the same inheritance pattern as red-green color blindness, which affects 1 in 20 males, and everything in between.

So are there variations in the mitochondria that cause slightly milder traits?

Then yes there are, inevitably, and we then get into a philosophical question of what genetic disease is.

But that's why we have the HFEA, That's why a treatment license needs to be applied for when it is a new disease.

Well, it's very, very akin to cloning technology and we've had that debate right from the start of Dolly the Sheep.

Cloning technology was never really there to make lots and lots of clones of human beings a la Star Wars.

It was there for specific medical reasons.

So in many ways, the technologies are similar to 1 another and could help 1 another out.

So the idea of spinal cord replacement, tissue replacement, new organs, that sort of thing, it has its applications in that area.

So this technology obviously has a lot of potential And while we need to ask ourselves the ethical questions along the way, what do you find most exciting about it?

So I think 1 of the things that will happen in the coming years is that we'll see a far greater democratisation of the IVF process.

At the moment, although you can get it on the NHS, it's very patchy and maybe just 1 or possibly 2 treatments.

So really, it's something that's only for the rich and middle classes right now.

So with this technology, with things like pre-implantation genetic testing, and indeed the whole of IVF, what we need to do is to bring the cost down such that we democratise the process and it becomes a lot more available to many, many more people.

We know that our population will grow for a little while, but now people are having babies much later because we're healthy and we're living longer.

But the biology of women's eggs is such that they are chromosomally far more fragile beyond about the age of 35 and yet people want to have children beyond the age of 35 because they're you know younger and fitter and healthier.

So after about 30 or 40, 50 years, what we may well experience is a bit of a population crash and so we need to get the science, the medicine and the social science in place so that IVF can be part of that solution.

You can read our science editor Ian Samples' exclusive on this story at theguardian.com.

Before I go, another reminder to listen to The Guardian's Cotton Capital podcast, looking at the Guardian's links to transatlantic slavery.

In the sixth and final episode of the series, Cotton Capital editor and Guardian journalist Maya Wolfe Robinson looks at the subject of reparations and how the Guardian plans to address revelations unearthed in the investigation.

If you haven't already, search for Cotton Capital wherever you get your podcasts and hit subscribe.

The producer was me, Madeline Finlay, the sound design was by Tony Onuchukwu, and the executive producer was Ellie Burey.


Speaker 0: This is The Guardian.

Speaker 1: This week, The Guardian broke the news of a first in the field of fertility science in the UK.

Speaker 2: Now the first baby created from 3 genetic parents has been born in the UK. The breakthrough is aimed at stopping a mother passing on defective genes to a child.

Speaker 1: The pioneering technique developed by doctors at the Newcastle Fertility Centre, is known as mitochondrial donation treatment, or MDT. Mitochondria provide energy to the cell and fuel the body. So when these are abnormal, a person can be severely affected. This could be anything from brain damage, muscle wasting, heart failure to blindness. Conditions can even be fatal within days or even hours of birth.

So this new technique holds a lot of promise for those impacted. But there are still plenty of unknowns about long-term outcomes, what these changes could mean for subsequent generations, and how the technology could be applied in the future. From The Guardian, I'm Madeline Finlay and this is Science Weekly. Darren Griffin, you're a professor of genetics at the University of Kent and you've done lots of research into genetic diseases and reproduction. So I'm keen to understand how significant this news is that the first baby has been born in the UK with DNA from 3 people.

Speaker 0: Yeah, it's worth unpacking it a little bit because it's a technology that we've known about for some time. So I've been aware of it for about 10 years, but it was being talked about before then. In many ways, it's a very obvious thing to do. The technology itself isn't a million miles from the so-called cloning technology, the nuclear transfer. We were certainly aware from conferences that this treatment was happening.

We were certainly aware that there had been treatment licences and that patients had undergone treatment.

Speaker 1: And the UK isn't the first country to create babies using MDT. In 2016, a US doctor announced the world's first MDT birth. But in each case, this technique is being used to prevent harmful mutations, abnormal mitochondrial DNA, from being passed from mothers to their children. So just give me a sense of how this works.

Speaker 0: Although the vast majority of our DNA resides in the nucleus, There's a tiny bit that resides in somewhere else, which is a mitochondria, which is sometimes referred to as the power packs of the cell. Now if that DNA is compromised, if it has a mutation, then we know that it can cause some pretty severe diseases. So the way that this works is that the patients receive the mitochondrial DNA from a donor but the vast majority is still from the biological parents.

Speaker 1: So let's take a deeper dive. You've got majority DNA from the parents, but you've got this part of the DNA from a third party donor. So how is this treatment actually done?

Speaker 0: It's not a million miles from going into an IVF clinic and having regular treatment. And at that point, an embryo is then produced from the parents that the vast majority of the DNA is from those parents because it's in the nucleus. That nucleus is taken out because the mitochondrial DNA might well be affected with this disease. We take the nucleus out and put it into a donor egg that has healthy mitochondria. So it's all done under a microscope, under micromanipulation.

When that nucleus is then inserted, it has all the DNA from the parents themselves, all the genetic traits that they would hope to pass on, but this tiny amount that has the healthy mitochondria in it that's not part of the nucleus.

Speaker 1: And I know there's an alternative method where the nucleus of the mother's egg is swapped into the donor egg before it's fertilised with the same outcome, parent DNA with the donor mitochondria in an egg that can then be implanted into a womb. It's quite incredible but is there any other way to prevent a baby from inheriting mutated mitochondria?

Speaker 0: Well, 1 could of course undergo prenatal diagnosis, so establish a pregnancy and then ask the question if the child is affected, the child in the womb is affected, whether you undergo a termination. I'm not aware at the moment of any effective treatment of children that are born with the disease, there are certain things that you possibly could do to mitigate depending on the disease to mitigate the symptoms but they would still always have the disease. So in terms of ensuring that they're born without it, it is a very very effective treatment in that sense. Anything else, so if it was some sort of gene editing therapy, you've got to bear in mind that there are lots of mitochondria in the cell where there's only 1 copy of the nuclear DNA, so you would have to try and be able to edit sufficient numbers of mitochondria in that cell. And that brings a whole set of other ethical questions along with it.

Speaker 1: Now I want to get into some of the ethical questions, but first off, you said this was a really effective treatment, but I wonder if there are any risks involved in doing it.

Speaker 0: I think the first thing we have to say is that any treatment that has the power to do good also has the power to do harm. You can take a paracetamol, for instance, for a headache, take too many of them, it could affect your life. So we always have to balance those things. The 1 big unknown, of course, is that although the babies are born healthy in 20, 30, 40 years, is there some sort of knock-on effect thereafter? On the balance of probabilities, we think not, or we think that it would be very minor, but of course we never know for sure until we've followed these children up in 20, 30, 40, 50 years.

And when we consider the alternative that the children will be born with these severe diseases and children will continue to be born, we have to consider what is a lesser of 2 evils and in my personal opinion that should be somewhat of a no-brainer.

Speaker 1: Recent research has found that in some cases, the tiny number of abnormal mitochondria that are inevitably carried over from the mother's egg to the donor egg can multiply when the baby is in the womb. This is called reversion or reversal and it could lead to disease in the child. According to Dagan-Wells, a professor of reproductive genetics at the University of Oxford who took part in the research, the reason why reversal is seen in the cells of some children but not others isn't fully understood. As Darren said, now scientists will be monitoring the babies who have been born using this technique to see what happens next. So Darren, I'd really like to talk through some of the ethical considerations here because it seems like a no-brainer to provide this treatment to somebody who could have a very serious genetic disorder.

So what kind of things were scientists thinking about beforehand?

Speaker 0: I think we need to look back at the UK's history in this area. And of course, when something new comes along, it raises alarm bells, the yuck factor, if you like. Now, you think back in 1978, the UK was the pioneer of IVF. In the 1990s, pre-implantation genetic testing. Then we had the whole thing surrounding savior siblings.

And in each of those cases, the science went alongside some very sensible regulation. And that's why the HFEA was formed, the Human Fertilization and Embryology Authority. Now I agree with you, I think that it should be a no-brainer because the alternative is children dying, being born with very severe diseases, having a very, very poor and short quality of life. That's not to say that it doesn't raise ethical questions. Of course, when you are considering that there is a tiny bit of someone else's DNA, do they have any legal rights to access to this child?

Well, that's an interesting question. It's 1 of the things that you just need to consider and perhaps you can deal with through legislation. The term three-parent IVF has never been 1 that I liked. The parents are the biological parents in the nuclear DNA and that's it. And safety is always an issue and my colleagues in Newcastle I know you know 1 of the best groups in the world for doing this and I know that they would do this very very safely.

But when you start rolling this out to many, many clinics across the world, you then have to have a regulatory procedure in place, a training procedure in place, a quality assessment procedure because not every 1 of those embryologists necessarily would be as highly skilled, you know, they might be relatively new to the job, as the people who are at the very top of the game in Newcastle. Other than that, I think we start getting into arguments of people say, oh well you're messing with the germline and you say well just think about the practicalities of this for the moment this is something that's only passed down the maternal line so as soon as a male appears in that germline then this issue would would go go away you know so while ever there are female to female transition, yes, that DNA would persist. But the first time a male is born in that line, it would go away. So, it's always a question of benefit over risk. And in this case, I really, really encourage people to think about what are the alternatives and to turn the ethical question another way around.

Given that we've got the abilities to do it, is it unethical not to do it in that case?

Speaker 1: At the moment, this is being used for, as you've said, very serious diseases, but could it be used for anything else? Are there other applications that we could see in the pipeline?

Speaker 0: We get to the stage of considering what is a genetic disease and this applies to the whole of prenatal genetic testing as well, that when you think that there are diseases, these are not mitochondrial diseases, but diseases such as Duchenne muscular dystrophy, which is highly debilitating, has the same inheritance pattern as red-green color blindness, which affects 1 in 20 males, and everything in between. So are there variations in the mitochondria that cause slightly milder traits? Then yes there are, inevitably, and we then get into a philosophical question of what genetic disease is. But that's why we have the HFEA, That's why a treatment license needs to be applied for when it is a new disease. Could we use it for other things?

Well, it's very, very akin to cloning technology and we've had that debate right from the start of Dolly the Sheep. Cloning technology was never really there to make lots and lots of clones of human beings a la Star Wars. It was there for specific medical reasons. So in many ways, the technologies are similar to 1 another and could help 1 another out. So the idea of spinal cord replacement, tissue replacement, new organs, that sort of thing, it has its applications in that area.

In that area.

Speaker 1: So this technology obviously has a lot of potential And while we need to ask ourselves the ethical questions along the way, what do you find most exciting about it?

Speaker 3: So I think 1 of the things that will happen in the coming years is that we'll see a far greater democratisation of the IVF process. At the moment, although you can get it on the NHS, it's very patchy and maybe just 1 or possibly 2 treatments. So really, it's something that's only for the rich and middle classes right now. So with this technology, with things like pre-implantation genetic testing, and indeed the whole of IVF, what we need to do is to bring the cost down such that we democratise the process and it becomes a lot more available to many, many more people. We know that our population will grow for a little while, but now people are having babies much later because we're healthy and we're living longer.

But the biology of women's eggs is such that they are chromosomally far more fragile beyond about the age of 35 and yet people want to have children beyond the age of 35 because they're you know younger and fitter and healthier. So after about 30 or 40, 50 years, what we may well experience is a bit of a population crash and so we need to get the science, the medicine and the social science in place so that IVF can be part of that solution.

Speaker 1: Thanks to Professor Darren Griffin. You can read our science editor Ian Samples' exclusive on this story at theguardian.com. Before I go, another reminder to listen to The Guardian's Cotton Capital podcast, looking at the Guardian's links to transatlantic slavery. In the sixth and final episode of the series, Cotton Capital editor and Guardian journalist Maya Wolfe Robinson looks at the subject of reparations and how the Guardian plans to address revelations unearthed in the investigation. If you haven't already, search for Cotton Capital wherever you get your podcasts and hit subscribe.

And that's it for today. The producer was me, Madeline Finlay, the sound design was by Tony Onuchukwu, and the executive producer was Ellie Burey. We'll be back on Tuesday. See you then.

Speaker 0: This is the Guardian.

See all Science Weekly transcripts on Applepodcasts

First UK baby born with DNA from three people: what happens next?