Earlier this month, a baby with DNA from three individuals—one man and two women—was born for the very first time in the UK. This procedure—known as mitochondrial donation—isn’t new but it is highly controversial and risky. It also raises an important question: should we even be doing this—just because we can?
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Wtf is a ‘three parent baby’?
The popular nickname for the procedure is actually misleading. There are only two parents but the procedure involves three individuals: mother’s egg + donor egg + father’s sperm. The primary purpose is to fix defects in a specific kind of DNA in the mom’s cells.
An intro to mtDNA: First, a Biology 101 refresher on what a human cell looks like:
As we learned in school, our DNA is primarily stored in the nucleus—a total of 20,000 genes. But around 37 are stored in the mitochondria—which float around in the cytoplasm. The mitochondria are tiny organelles that supply our cells with energy—and these genes are known as mitochondrial DNA or mtDNA. Now, mtDNA is only inherited from the mother. When the sperm and egg fuse, the father’s mtDNA is entirely removed—for reasons that scientists don’t really understand.
The problem: is that the mother’s mtDNA can sometimes contain defects—and this in turn can create two kinds of health issues. The first is mitochondrial diseases—which are rare but affect multiple organs and can be fatal. An example is Leigh syndrome—which leads to the progressive loss of mental and movement abilities—and typically results in death within two to three years of birth due to respiratory failure. There are around 300 such genetic diseases—of varying severity.
Also, infertility: A number of couples suffer from unexplained infertility—where there is no discernible cause. For reasons scientists don’t entirely understand, the mitochondria play a key role in conception—perhaps due to the energy needed by a cell to divide properly. And there is some evidence that ageing may affect our mitochondria—especially in women’s eggs.
The solution: is Mitochondrial Replacement Therapy—where the mitochondria of the mom’s egg is replaced with the mitochondria of the donor egg. Also known as mitochondrial donation.
And how in the world do they manage that?
There are two techniques—involving the unfertilised and fertilised egg, respectively.
Procedure #1: Scientists extract the nuclei from the eggs of the mom and the donor. They replace the nucleus of the donor egg with that of the mom. The result: healthy DNA in the mom’s nucleus is encompassed in the cytoplasm of the donor—which contains healthy mtDNA. This healthy egg can be fertilised by the father’s sperm.
Procedure #2: Scientists first fertilise two eggs—that of the mom and the donor—with the sperm of the father. This is called a zygote. They extract the nucleus of the mom+dad zygote and transfer it to the donor+dad zygote.
The two processes look something like this:
Point to note: The donor is not considered to be a biological parent—and remains anonymous unless the child asks for the information.
The history of MRT: We don’t really know how many babies have been born via mitochondrial donation. Many clinics do not release this information. And the procedure is not encouraged in all countries—for example, the United States.
Back in the 1990s, US researchers were the first to inject fluid from healthy eggs—including their mitochondria—into eggs of women who had been through several rounds of failed IVF. The results were dismal:
The team tried their technique 30 times in 27 people, and 17 babies were born. But two foetuses developed a genetic disorder, in which they lacked an X chromosome. One of these pregnancies resulted in a miscarriage, the other was aborted.
As a result, any MRT procedure needs special FDA approval—which is almost impossible to get.
The Mexico case: In 2016, a New York doctor travelled to Mexico to perform MRT for a Jordanian couple. The mother carried mtDNA for Leigh Syndrome. She had suffered four miscarriages and had given birth to two children who did not survive past the age of six. The baby boy was the first to be born using the spindle technique—using the unfertilised egg of the mother and donor. Point to note: the procedure took place in Mexico because—as the lead doctor acknowledged—”there are no rules.” The baby was healthy with no known issues. You can see the baby in the one-minute video report below:
The Newcastle trial: In 2015, the UK became the first country to launch a regulated trial at Newcastle University. It did not release any information about the trial until early May—when authorities finally acknowledged the first birth in the UK. In fact, they confirmed there have been five such births—but shared zero details.
Point to note: The procedure is legal in Greece, Ukraine and Australia, as well.
Ok, sounds great! What’s the problem?
The ‘reversion’ problem: New research shows that MRT is not always effective. In March, MIT Technology Review revealed two cases where the mtDNA from the mom increased over time.These were part of a study conducted in Greece—with 25 heterosexual couples suffering from infertility. The 85 fertilised eggs resulted in six successful pregnancies—with the babies being born between 2019 and 2020:
For five of the babies, the levels of their mother’s mtDNA has remained low, at less than 1%. But something strange has happened in one of the children. At the embryo stage, less than 1% of this child’s mtDNA came from the woman with “bad” mtDNA, while over 99% came from the donor. But by the time the baby was born, the balance had shifted—with between 30% and 60% of the mtDNA coming from the mother. “It’s almost 50:50,” says Wells. “That’s a huge swing.”
In another unpublished case in Ukraine, a baby boy’s mtDNA from his mother had jumped as high as 72% at birth. Oddly, his elder sister—who was born using the same procedure—stayed stable at 1%.
Why this is a big deal: Luckily, in the above cases, the problem was merely that of infertility. The mothers did not have any genetic defects in their mtDNA—in which case the risk of the babies carrying the disease would have been as high as 60%. Most scientists do not know how many babies will be affected by reversion. Some doctors estimate it may be as high as 20%—as in one in five babies. If so, are those odds acceptable when mitochondrial diseases are involved:
Heidi Mertes, a medical ethicist at Ghent University, says that it is important to think about what would-be parents would do if the technology were not available. If they would try for a baby regardless, then perhaps an 80% reduction in the risk of passing on disease-causing mtDNA is acceptable. But if they might otherwise consider using a donor egg, or adopting a child instead, then “those are better alternatives,” she says.
The importance of ‘genetic connection’: Procedures like MRT emphasise the biology rather than the experience of being a parent:
Experimental treatments like MRT also help to reinforce the idea that it’s very important for parents to have a genetic connection to their children, says Mertes. “Wouldn’t it be wiser to question whether it’s so important to have that genetic connection if the price you have to pay is a health risk for your child?” she asks.
But, but, but: Such procedures also offer same-sex couples the possibility of a biological connection with their child—which isn’t possible with surrogacy or donor sperm. A lesbian couple could use both their eggs plus donor sperm—establishing a genetic link to both the baby’s moms.
In fact, the next frontier of such technologies could make this possible for gay couples:
Scientists are working hard to turn human skin and blood cells into egg and sperm cells in the lab. They’ve already done this in mice. If they can manage to do it in people, the possibilities for biological parenthood expand even further. The first application would be to enable same-sex couples to have genetically related children. You could, for example, turn the skin of one man into an egg cell, and fertilise it with the sperm of his partner to create an embryo.
The bottomline: We are not entirely convinced that the great might of medical innovation should be focused on enabling biological parenthood—however great the odds. We leave you with this quote from a bioethicist that resonates with us: “An obsession with biological connectedness tends to make non-biological parents be seen as second-best parents, and I think that’s actually quite offensive.”
New Scientist (login required) has an excellent overview of ‘3 parent babies’. We also highly recommend MIT Technology Review’s articles (limited free views) on reversion and the definition of a parent. The Guardian has the most on the recent UK birth. Deutsche Welle has more on using gene-editing techniques to create designer babies.