The news of eight babies conceived and born in the United Kingdom, each with genetic material from three parents, has reignited bioethics debates on in vitro fertilization, gene editing, and the role of DNA in human identity.
The medical community had a strong reaction last week to a groundbreaking new study published in the New England Journal of Medicine documenting that eight children conceived via a controversial artificial reproductive technology procedure have gone on to live healthy lives largely free of complications.
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The process that gave these children life, called mitochondrial transfer, has been billed in the media using the shorthand “three-parent IVF,” but the process is much less science fiction than it sounds.
At the heart of the process are the mitochondria, the organelles called the “powerhouse of the cell” because they make energy. Mothers pass their mitochondria to their children. If a mother’s egg cell has mitochondrial dysfunction, as a result of damaged mitochondrial DNA, then that will be passed to her child, likely resulting in potentially severe chronic diseases.
Mitochondrial transfer uses the IVF process to mix the gametes, or sex cells, of three parents: the egg and sperm of the biological mother and father, and the donor egg that is unaffected by mitochondrial disease.
The hope of parents is to prevent debilitating mitochondrial diseases from being passed down to their children, but opponents argue that creating a child with three genetic parents is unnatural.
Vardit Ravitsky, president of the nonpartisan bioethics group The Hastings Center, told the Washington Examiner that writing about this process, even in the scientific community, is a thorny issue.
“It’s a very significant choice, whether you say ‘three-parent babies,’ which is very emotionally loaded, versus ‘mitochondrial transfer,’ which is very technical and neutral,” Ravitsky said.
IVF has long been an ethically complicated issue, becoming a flashpoint during the 2024 election, especially the question of whether embryos created via IVF have personhood rights or can be ethically destroyed or frozen indefinitely.
But mitochondrial transfer is not a mainstream part of the IVF debate in the United States because it is not expressly legal in the country. It technically falls under the murky regulations regarding cloning procedures for the purposes of reproduction.
Nevertheless, the pioneering of the technology opens a range of ethical matters to consider, including the consequences of gene editing and the role of DNA in shaping a person’s identity.
Process of mitochondrial transfer
There are two different types of methods for mitochondrial transfer, depending on the moment of fertilization.
The first type of mitochondrial transfer occurs before the creation of the single-celled embryo, called a zygote. In this process, the nuclei are removed from both the mother and donor eggs, and then the mother’s nucleus is transferred into the donor egg cell. Fertilization then commences as it would during the traditional IVF protocols.
The second type of mitochondrial transfer occurs after the mother egg has been fertilized, with the mother’s and father’s DNA transferred into a denucleated donor egg.
Dr. Robert McFarland, a British physician-scientist and the lead author on the groundbreaking study published last week, confirmed to the Washington Examiner that, in these cases, both the mother and donor eggs were fertilized by the father’s sperm before nuclear transfer took place, technically creating two embryos.
However, the nuclear transfer in these cases occurred at a specific time in the zygote-making process before the mother’s and father’s DNA fused. At this point in the process, the mother’s and father’s so-called “pronuclei” have not joined together to make a full nucleus, the genetic blueprint of their distinct new child.
“From an ethical perspective it is worth considering that while two eggs are fertilised to create two embryos, both are manipulated at a stage prior to fusion of the pronuclei from both parents – the event which creates a new genetically unique zygote,” McFarland wrote via email.
Disease prevention or genetic manipulation?
Supporters of mitochondrial transfer see the controversial procedure as treating a patient and preventing debilitating physical conditions later in life.
An estimated 1 in 5,000 people worldwide have a mitochondrial disease, according to the Cleveland Clinic.
Mitochondrial diseases can affect neurological and musculoskeletal function as well as the heart, kidneys, liver, and pancreas. These conditions can be severely life-limiting, with symptoms ranging from muscle weakness and pain to severe gastrointestinal problems, seizures, and migraines.
Advocates of IVF and mitochondrial transfer see the procedure, either before or after conception, as a way to prevent patient suffering.
Opponents, though, view it as too close to more invasive forms of genetic manipulation of embryos, messing with a natural process.
Ravitsky told the Washington Examiner that she rejects this type of “playing God” argument against mitochondrial transfer.
“I think that if you’re concerned about playing God, then you might as well reject modern medicine,” she said.
Role of mitochondrial DNA
Ravitsky said mitochondrial transfer is “deeply different than gene editing,” such as through CRISPR technology, because mitochondrial DNA does not play the same role as cellular DNA in the nucleus for creating a personal identity.
She said conflating nuclear gene editing and mitochondrial transfer is “scientifically misguided” because the latter “has basically no consequences of that type that editing the nuclear DNA would have.”
“It’s the [nuclear] DNA that makes us who we are, that’s responsible for our entire phenotype,” Ravitsky said. “Our physical traits, or some of our personality traits, our decisive risk that we carry, everything that we are, whereas the mitochondria, as far as we know, is not responsible for any trait. It’s just a source of energy.”
Dr. Aaron Kheriaty, a psychiatrist and bioethicist at the conservative Ethics and Public Policy Center, told the Washington Examiner that he does not buy the argument that mitochondrial DNA is negligible, especially because we do not understand everything genes do for the body.
“We don’t know what most genes do, including the 37 genes in the mitochondria,” Kheriaty said. “At least, we don’t know everything they do.”
He also said mitochondrial DNA must do something more than just power the mitochondria themselves because of the way diseased mitochondria manifest in physical symptoms for a patient.
If mitochondrial DNA was insignificant, Kheriaty reasoned, there would not be advocates of the procedure “bending over backwards and going through an enormously complicated process to change the mitochondrial DNA.”
DNA and identity
Any discussion of DNA evokes the question of identity, but there is a great debate about how much of a difference mitochondrial DNA actually makes.
Kheriaty argued that, even if mitochondrial DNA only plays a small role in a person’s identity, it still may matter to the child in some fundamental, psychological way as they mature.
“We’re tinkering with something here that’s very deep,” Kheriaty said, “and, you know, for a child to discover that ‘I have a second genetic mother who contributed something to who I am,’ right, ‘maybe not most of who I am, maybe not the most important parts, maybe not the most obvious phenotypes, but something,’ you know, we don’t actually know yet what that’s going to mean to that person.”
Children conceived through conventional artificial reproductive technology using donated sperm or eggs can have problems growing up, not knowing their parentage.
A 2021 study from professors at Harvard Medical School’s Center for Bioethics found that people conceived via sperm or egg donation “experienced significant distress upon learning about the nature of their conception.”
About 85% of the 143 people surveyed reported a shift in their “sense of self” upon learning about their conception, and half sought psychological help to cope. Three in four said they thought “often or very often” of the nature of their conception.
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Kheriaty said the ethical implications of identity surrounding mitochondrial transfer “doesn’t automatically mean that it’s wrong,” but he said people must tread with caution.
“We’re touching on something and we’re tinkering with something that’s deeply human, that’s deeply embedded in our collective experience, in our society, in our laws, in our notions of identity, and selfhood,” he said.