Three Parent Babies? Should we be concerned?
Headlines including the phrase “three-parent-baby” have appeared in the UK press this week after a report in the Guardian newspaper. [i] Journalists made a Freedom of Information request to the Human Fertilisation and Embryology Authority (HFEA) asking if any babies had been born who were conceived through a novel technique called Mitochondrial Donation Treatment (MDT) which results in them having genetic material from three people. In response, the HFEA confirmed that at least one, but fewer than five, such babies have already been born in the UK. This is not a world first – that was in the USA in 2016 – but it is the first confirmation that this has happened in the UK since 2015, when the UK became the world’s first country to approve techniques for MDT after a vote in Parliament.[ii] The technology has been developed and these babies conceived with the help of a team based in Newcastle Upon Tyne led by Professor Doug Turnbull and Professor Mary Herbert. It has been hailed as a breakthrough in treating mitochondrial diseases, which are rare but can be devastating, resulting in premature death or progressive illness.
The science behind MDT is truly astounding and not a little confusing for those who are not scientifically educated. I will do my best to explain it in accessible terms. DNA is a chemical from which genes, and the chromosomes that carry them, are made. Genes are pockets of information that code for the proteins that are the building blocks of bodies. In the natural process of procreation, we all inherit two kinds of DNA: nuclear, which is contained in the nucleus of the cell, and mitochondrial, which is contained in the mitochondria. The mitochondria are one of several kinds of organelles contained within cells, which are structures that fulfil various functions. Reports about children conceived through MDT have stressed that a tiny percentage (perhaps 0.1%) of the children’s DNA comes from the third person. This refers to the fact that the mitochondrial DNA is tiny compared to the DNA contained in chromosomes in the nucleus and, therefore, a small fraction of the total genetic material in our cells. The figure is, however, somewhat misleading for reasons I will explain below.
Nuclear DNA, along with influences from our environment, determines most of our inherited characteristics, from obvious things like hair and eye colour to non-visible things like our risk of developing many diseases. Half of it is provided by the father, in a sperm cell (spermatozoon), and half from the mother, in the nucleus of an egg cell (oocyte). The sperm and egg cells combine to form a new life, initially known as an embryo (or a zygote in the very beginning). This normally happens in the body during sexual intercourse, but it can also be done in a laboratory (as it is in cases of MDT) using sperm provided by a man and eggs harvested from the ovaries of a woman surgically after she has been treated with hormones to ‘ripen’ her eggs. Some mixing and mutations happen in the process, meaning that each embryo has some new variations in its DNA (on average around 200) that differ from either parent, but we can say that around 50% of our genes come from each of our parents. The sperm cell provides nothing other than the DNA, but the egg cell provides us with everything needed to begin life – it contains all the organelles needed to sustain life and facilitate the multiplication of the cell by producing proteins.
The egg cell, like all human cells except the sperm cell, is immensely complex. It can be likened to a miniature city, with each organelle having a specific function like the various buildings in a city. The egg cell is the largest cell of the human body and the only one large enough to be, theoretically at least, visible with the naked eye, being approximately the size of a small grain of sand. The specific function of a mitochondrion (plural mitochondria – each cell contains many) is to convert energy in nutrients obtained from food into a form usable by cells (the chemical adenosine triphosphate or ATP) through a process called cellular respiration. If the cell is a city, the mitochondria are the power stations.
Because the mitochondria are found in the egg cell but not the sperm cell, the mitochondria of the new embryo come only from the mother. Whether you are male or female, these powerhouses came from your mother. If you are a man you cannot pass them on but if you are a woman all your children, male or female, will receive their mitochondria from you. This makes the mitochondrial DNA an excellent tool for tracing descent through the female line. Biologically speaking, this means mothers have a special role to play in our ability to make use of nutrition. Mothers also have a special role in providing nutrition – initially to the early embryo through her blood supply, then via the placenta and, after birth, if she chooses and is able to breastfeed, through her breast milk. Biologically, motherhood entails protection and nurture.
The difference compared with this normal pattern in babies conceived through MDT is that they have nuclear DNA from one woman and mitochondrial DNA from another. MDT can be achieved through one of two mechanisms:
Maternal spindle transfer (MST) – the woman who carries a mitochondrial disease has her eggs harvested (woman a), as does another woman whose mitochondria are healthy (woman b). The nucleus is removed from an egg from each woman. The nucleus of the egg from woman b is discarded and replaced with the nucleus from woman a’s egg. We now have an egg with woman b’s mitochondrial DNA and woman a’s nuclear DNA. It can be combined with a sperm cell from the man of woman a’s choice (her partner or a donor) to produce an embryo.
Pronuclear transfer (PNT) – the difference from MST is that sperm is injected into an egg from woman a (who carries a mitochondrial disease), beginning the process of fertilisation that leads to a new embryo. The nuclei of the sperm and egg will become pronuclei – the phase before the genetic material combines together – and these pronuclei will be removed and injected into an embryo produced using woman b’s egg which has already had its nucleus removed.
The end result is the same in both cases – we now have an embryo with DNA from three people. This can be implanted into the womb of woman a so that she can carry the baby and give birth to it.
As indicated above, advocates of MDT tend to play down the significance of the combination of three people’s DNA, for example by emphasising that only a small percentage comes from woman b. The 0.1% headline is misleading, however, because it considers the mitochondrial DNA only as a percentage of the total genetic material in the cell. When we consider the nuclear DNA and mitochondrial DNA separately, we should say that these embryos will have 50% of their nuclear DNA from each of two individuals – one man and one woman – and 100% of their mitochondrial DNA from another woman. The term “Mitochondrial Donation Treatment” (MDT), although used by the HFEA,[iii] is also somewhat misleading, since what has been donated is not only the mitochondria, but the whole of the egg cell minus the nucleus. Whilst the mitochondria contain the only genetic material, which is what will be replicated and passed on to other cells and down the generations, the other organelles have been created in the body of the third person. Since they are also essential for life, she has played a crucial part in the conception of the new embryo.
The mitochondrial diseases MDT has been developed to treat result from mutations in the mitochondrial DNA. These mutations can occur in a single egg cell or the new embryo, but they are often inherited from the mother, being present in the mitochondria in all her eggs. Women who discover they are carrying a severe mitochondrial disease are often advised not to have further children as mitochondrial diseases are incurable. The new technologies of MST and PNT open the possibility that women carrying mitochondrial DNA can have children who are genetically related to them because they provide their half of the nuclear DNA. As with any new medical technology, however, we must consider the safety and ethical implications of MDT.
Perhaps the most obvious concerns about this technology relate to its safety. Will the babies conceived through MDT be healthy? Might the process create other problems not yet anticipated? As with any scientific development, the effects and side effects of MDT can only be measured accurately over a long period of time after multiple uses of the technique. As Professor Robin Lovell-Badge, from the Francis Crick Research Institute, is quoted as saying: "It will be interesting to know how well the mitochondrial replacement therapy technique worked at a practical level, whether the babies are free of mitochondrial disease, and whether there is any risk of them developing problems later in life”.[iv] We must remember that real individuals are in view here. Only as they develop to and through adulthood will we be able to tell if MDT has had a negative impact.
This risk of harmful consequences is all the more important when we remember that the embryo’s genes will be inherited by the individual’s children. Any problems arising from MDT will be passed on to future generations too. This amplifies the safety concerns and may cause some people to be wary of such new technologies, especially since they had had limited testing in non-human primate species (those whose genes share the most commonality to ours) before being used in human beings. Some medical ethicists argue that this concern alone should mean that medical scientists should never edit the DNA of embryos. Some may add that it is unacceptable to do something to an individual before a point when he or she can consent (as an embryo clearly cannot) that may have a lasting effect on his or her health. I am not convinced that we must be as restrictive as that, but we certainly should be extremely cautious, and I am not certain that enough research was done into MDT before beginning to use it in human beings.
So far, I have commented primarily on safety concerns. Some geneticists suggest those are “the only serious ethical issue” with this technology.[v] But there are other ethical considerations besides the risk of harm. Our view towards MDT will depend on what we believe to be right or wrong concerning the use of embryos and the nature of families and parenting.
Concerning the use of embryos, the key question is what the status of an embryo is. Science confirms that an embryo is a genetically unique, living, human individual. Some ethicists suggest it should not be regarded as a human person because it has no self-awareness and therefore argue that experimentation on, and destruction of, embryos is acceptable. But they have created a category of “human non-persons”, to which it could be argued that other human beings belong, for example those with severe intellectual disabilities or advanced dementia. The definition of personhood cannot be established through science. It is a philosophical or religious question.
Within a biblical worldview, there can be no such thing as a human non-person. Every living human being descended from the first human beings who were created in the image of God is a human person in relationship to God and bearing his image. The dignity that identity confers does not lessen due to disability or age. Every embryo is, therefore, a human individual known and loved by its creator, God, and afford embryos should be afforded the same value and dignity as any human being. If this is correct, then the PNT technique is problematic because the nucleus from one embryo is destroyed. Killing one individual to allow another individual to be conceived without disease cannot be ethical. This objection does not apply to the MST technique, in which an egg cell nucleus is discarded rather than an embryonic nucleus, but what about the ethics of family and parenthood?
A 2015 BBC headline about MDT read, “Three-person babies - not three-parent babies”.[vi] This confident declaration was apparently intended to allay fears raised by headlines that referred to “three-parent babies”, but is it correct? The article was based on comments by Professor Turnbull, who pioneered MDT. It describes those who provide the nuclear DNA as ‘parents’ and the woman who provides the mitochondrial DNA as a ‘donor’. It also introduced the misleading 0.1% figure and quoted Prof Turnbull describing “three-parent-baby” as “a catchy headline”, adding, “Do I think it's accurate? Of course I don't”. But on what basis does Turnbull make this assertion? Simply because he says that a woman who provides mitochondrial DNA to a child should not be seen as a parent? The article does not provide a definition of a parent. How can we judge if someone is a parent if we do not have a clear definition?
Parenthood is comprised of various elements – both biological and sociological. We may think of those who raised us as our parents even if we are not biologically related to them, but we still had biological parents. Normally, people have a biological father, who provided the sperm cell, and a biological mother, who provided the egg cell and bore the embryo through pregnancy and gave birth to the child. With modern medical techniques, these two aspects of biological motherhood can be separated, as an embryo formed with one woman’s egg can be implanted into the womb of another woman. So, we can speak of a genetic mother and a birth mother. Normally, people have two genetic parents as all of their genetic material comes from one man and one woman. Indeed, definitions of genetic parents tend to describe them as the man who provided the sperm and the woman who provided the egg, but such definitions are made without considering MDT. A more accurate definition of a genetic parent is a person who passes genetic material to an embryo that shapes its development. By that definition, people conceived through MDT do have three parents.
At this point, someone might accuse me of semantics. What does it matter, they might say, if the embryo has DNA from a third person? Surely such a small amount of DNA (0.1%) can make little difference and is basically negligible? To answer that objection, we need to understand more about what mitochondrial DNA does. The mitochondrial DNA contains 37 genes. [vii] In total, the human genome has somewhere between 20,000 and 25,000 genes, so the mitochondria carry at most 0.19% of our genes. Since the mitochondrial genes are, “principally concerned with the integrity of the respiratory (energy producing) chain”, some geneticists liken MDT to, “changing the batteries”.[viii] I find this analogy concerning for three reasons. Firstly, I object in principle to any parallel between human beings (or any created organism, for that matter) and machines. Changing the batteries in a device is clearly not of the same ethical significance as altering the genes of a person. Secondly, the analogy is misleading because PNT and MST do not simply change the mitochondria. The new embryo will have all the constituent elements of the egg cell of the third person, so this is a little more than simply a battery change. Thirdly, and most significantly, the suggestion that the mitochondrial DNA does not do anything other than ensure the provision of energy is wrong.
Advocates of MDT have suggested that it will have no impact on the characteristics of the resulting children other than to free them from the mitochondrial disease. In 2015, Prof Turnbull told the BBC, “Those mitochondria are not going to influence any of the characteristics of these children, they're going to provide healthy mitochondria”.[ix] This claim is in direct contradiction to findings from medical science, which is rapidly discovering more about how the mitochondrial DNA interacts with the nuclear DNA in our development. For example, Fabrizio Ghiselli and Liliana Milani write that, “Mitochondria have a central role in many fundamental processes of eukaryotic life, well beyond energy production”.[x] This is because the mitochondrial genes interact with the nuclear genes, affecting how they are expressed. Researchers have already discovered connections between variations in the mitochondrial genes and characteristics like adult height and liver and kidney function as well as certain diseases.[xi] The field of research is rapidly developing, and many more connections are likely to be discovered in coming years. Our analogy of the cell as a city may help explain this point. The parts of a city will inevitably affect one another – roadblocks in one place will create congestion elsewhere and products produced in one place will be distributed to others. If there are two sources of authority in a city (for example a mayor and a police chief), their policies will affect each other. So it is with the mitochondrial genes and the nuclear genes.
I do not mean to accuse Turnbull of dishonesty in 2015 when he dismissed the idea that mitochondrial DNA impacts characteristics of individuals beyond cellular energy production, since the reports I have cited in contradiction to his claim are from 2020 and 2021. Turnbull may have been ignorant of these facts when he made his statement to the BBC as the evidence may not yet have become clear. Even if that is the case, however, it is still concerning that he was ready to press on with his research and to make such an emphatic statement in the absence of any clear understanding of how mitochondrial DNMA influences development. This correction to a statement made in 2015 – the year when Parliament gave approval for the techniques Turnbull was eager to develop – shows, I suggest, that Parliament was premature in giving its approval. It should be a basic principle of medical ethics that no genetic alterations can be made to human DNA in living individuals without a very clear understanding of how the DNA that is to be altered affects the characteristics of the individuals. That is not the case with MDT.
Mitochondria are essential for life (we cannot live without them). Their provision is a vital part of parenthood. MDT separates two aspects of genetic motherhood. In nature, the mother provides both nuclear DNA (half of it) and mitochondrial DNA (100% of it). In MDT, these contributions are made by two different women. The woman who provides the egg cell with healthy mitochondria is more than a donor of something that enables two people to become parents. She is a contributor of genes that will make a significant difference to the child. She is a third parent. The provision of mitochondria, although not understood until modern times, is an essential aspect of motherhood and part of a definition of what is distinctive about mothers compared with fathers. Mothers are nurturers of life, not only when we are unborn and infants, but throughout life through the gift of the mitochondria.
Indeed, since the mitochondria are passed on from mother to child and do not change across generations of women, the woman who was the ‘third parent’ will also be a ‘fifth grandparent’ to the next generation, a ‘ninth great-grandparent’ to the third generation and so on. Strikingly, the percentage figures are worth revisiting in thinking about this. Whereas the percentage of nuclear DNA that comes from each of our forebears halves with every generation (50% from each parent, 25% from each grandparent, 12.5% from each great-grandparent etc.), the same does not happen with mitochondrial DNA. We have 100% of the mitochondrial DNA from our mothers, 100% from our maternal grandmothers, 100% from our matrilineal great-grandmothers and so on. Or, for those who want to quote the 0.1% statistic, we are saying that 0.1% of the DNA of every generation of women to come in that line will be from the woman who provided the mitochondria. This is not insignificant and should, I maintain, mean she is understood to be an ancestor of those generations and a parent to the first baby produced using her mitochondria.
I think it is indisputable that babies conceived through MDT do have three parents. This raises important questions. Will these children have a right to know this third parent? How will they feel about the fact? How does this involvement of a third person affect the woman who gives birth to and raises the child emotionally? These practical questions are significant enough, but what other ethical questions does this idea of three parent children raise? What does it say about our understanding of family? As a Christian, I believe God’s design for parenthood is that it happens in a context of a covenant commitment (marriage) between a man and a woman. For this reason, I am opposed to the idea of donation of genetic material by a third person, whether donation of gametes or of mitochondria. This action brings a third person into the relationship. I cannot agree with MDT for this reason.
The acceptance of MDT is something of a watershed for the UK. It establishes the principle that it can be acceptable to alter the genes of an embryo that will be inherited by its offspring. Will the idea of three-parent-babies become acceptable? Should couples who want to live as a threesome of one man and two women have the right to this procedure, not to overcome diseases, but to ensure they can have children genetically related to all three people? What about other changes to genes in egg cells, sperm cells and embryos? Would it be acceptable to edit other parts of the DNA to eliminate other diseases? If so, how far should that go? We might start with genes that cause disease and then move on to genes that merely increase the risk of a disease. The next step after that might be genes that enhance strength or longevity and then genes that give a preferred physical characteristic, perhaps eye, hair, or skin colour. Could we even create a genetic ‘master race’ of physically superior people? This is not simply a ‘slippery slope’ argument. It is a legitimate set of questions that follow from the advent of MDT babies. If it is acceptable to edit some human DNA, why not all?
The possibility of designer babies is very real with new medical techniques such as those used in MDT. As a Christian, I find that deeply troubling. In God’s good design, parenthood is chosen, but children are not. We choose to procreate, but we do not choose the children we receive. To introduce choice of the characteristics of our children into the equation is to undermine the unconditional love that should mark parenthood. That kind of love is only found from parents and is a vital source of security for developing children as well as a pointer to the greater fatherly love of God for his people.
We must not objectify children by designing the children we want to have or designing out the traits we do not want. Nor should we treat parenthood as a right. We must recognise the deep pain that comes from realising one is unable to have children or from having a child with a life-limiting condition. People in such situations need support and compassionate care and Christians should be at the forefront of providing it. But we must think twice before going to all and any lengths to ensure that people can have children. We must consider whether a specific technique is ethical. Couples facing issues with fertility must also consider how pursuing a particular path of treatment will affect them emotionally. For Christian couples, the key questions will be: (a) is this technique acceptable to God; and (b) can we keep trusting God together as we follow this path.
Recognising the risk of turning children into an object to be obtained at any price leads to another concern with new techniques like MDT – their immense cost. These techniques may become cheaper over time, but the need for high standards and close involvement of highly skilled people means it is unlikely to become affordable for everyone, at least in the foreseeable future. That means they will be the preserve of wealthy nations and, most likely, rich people. Is it right to put so much money and time into this kind of development when so many people live in poverty and so many other diseases are under-researched? I do not want to suggest we can neglect mitochondrial diseases altogether, but there are other, less problematic ways to counter them. We could focus instead on editing the mitochondrial DNA of the mother so she can pass on healthy mitochondria along with her nuclear DNA. We still need to consider safety, but we can avoid bringing a third parent into the equation.
A final thought is important as I round off this article. Many children in the world need loving parents to raise them. Adoption is an alternative possibility for couples who discover the woman is carrying a mitochondrial disease or any other inherited disease. I realise it is not the same as having their own children, but it does put both parents in the same position in relation to the child (this is not true of another potential solution for these couples, where they have an egg cell donated by another woman) and does not bring a third parent into the picture. It is also an act of compassion and is profoundly God-like, adoption being one of the images of salvation in the New Testament. In a world where many embryos are destroyed because couples have them produced for In Vitro Fertilisation (IVF) but then choose not to or are unable to have them implanted, it is also possible for such couples to adopt an embryo. [xii] The woman can have it implanted and carry it to term and give birth to it. That embryo will be saved from destruction.
We cannot undo what has already happened. The children conceived through MDT are precious individuals loved by God and with the same right to life as every person. I do hope, however, that the government and the scientific community might reconsider the ethics of this technology. I, for one, am in agreement with my friend Peter Saunders, who has described MDT as “unnecessary, (potentially) unsafe and unethical”.
[i] Sample, Ian (9th May 2023) ‘First UK baby with DNA from three people born after new IVF procedure’, The Guardian. Available: https://bit.ly/41rcCCQ [ii] Kmietowicz, Zosia (2015) ‘UK becomes first country to allow mitochondrial donation’, BMJ, 350: h1103. Available: https://bit.ly/3nNSgpJ [iii] Human Fertilisation and Embryology Authority, ‘MJitochondrial Donation Treatment’. Available: https://bit.ly/44NYcj8 [iv] Gallagher, James (10th May 2023) ‘Baby born from three people’s DNA in UK first’, BBC News. Available: https://bit.ly/41q9FTh [v] See the comment by Peter Turnpenny and Alan Fryer in response to a Christian Medical Fellowship article here: https://bit.ly/44OANOE [vi] Gallagher, James (1st Feb 2015) ‘'Three-person babies - not three-parent babies', BBC. Available: https://bit.ly/3NZiTmh [vii] Garcia, Iraselia et al. (2017) ‘The little big genome: the organization of mitochondrial DNA’, Front Biosci (Landmark Ed), 22: 710–721. Available: https://bit.ly/3Mftrwf [viii] Peter Turnpenny and Alan Fryer again from: https://bit.ly/44OANOE [ix] Gallagher, James (1st Feb 2015) ‘'Three-person babies - not three-parent babies', BBC. Available: https://bit.ly/3NZiTmh [x] Ghiselli, Fabrizio, and Milani, Liliana (2020) ‘Linking the mitochondrial genotype to phenotype: a complex endeavour’, Philosophical Transactions of the Royal Society B: Biological Sciences, 375(1790) Available: https://bit.ly/42qo6YC [xi] Yonova-Doing, Ekaterina et al. (2021) ‘An atlas of mitochondrial DNA genotype–phenotype associations in the UK Biobank’, Nature Genetics, 53: 982-993. Available: https://www.nature.com/articles/s41588-021-00868-1 [xii] Human Fertilisation and Embryology Authority, ‘Donating Your Embryos’. Available: https://bit.ly/3W85met