September 29, 2020

The Niche

Knoepfler lab stem cell blog

Myths about 3-person IVF mitochondrial transfer

It’s been somewhat of a helter-skelter time for the new technology often referred to as 3-person IVF or mitochondrial transfer as the UK considers whether to legalize this experimental technology for use in humans.

I believe that this technology is not ready now for use in humans and for more background on why as well as other opinions you can see articles here.

The admirable goal of this experimental 3-person IVF approach is to prevent transmission of mitochondrial diseases from mother to child, but it raises many complicated scientific and ethical questions. Like advocates of the use of this technology in humans, I too want to see new options for people with mitochondrial diseases to be able to have healthy families, but unfortunately this technology although well-intentioned could int reality end up doing far more harm than good, especially if implemented too soon.

The two main methods proposed for this technology are outlined in images from the UK HFEA.

3-person IVF
3-person IVF process.

Unfortunately in the fray, some myths have popped up that we now often see quoted in newspaper articles as facts.

Here are what I believe are the top myths or inaccuracies that have arisen and the facts that counter them.

Myth: This technology would cure mitochondrial diseases. Fact: The technology, even if proven successful and that’s a big ‘if’, would prevent some children from being born with mitochondrial diseases. It would not treat or cure them.

Myth: This technology has been conclusively proven safe in animals and would definitely produce healthy babies. Fact: Animal studies are mixed as to whether this approach is safe. Some that are limited in scope are encouraging, while others have raised serious warnings. More studies, particularly in primates, would be needed for a conclusive determination. As this technology is highly experimental it is unknown if the human babies produced would be healthy. In fact, it might put them at risk.

Myth: This technology would only be used for treating mitochondrial disease. Fact: One of the leading advocates of this technology in the US, Dr. Shoukhrat Mitalipov, has already asked the US FDA to approve this technology for treating infertility as well. Therefore, in addition to mitochondrial diseases this technology could well be used for infertility as well as for other purposes that even today’s backers might find not so clear-cut from a bioethical perspective.

Myth: This technology involves transfer of mitochondria. Fact: This technology does not involve moving mitochondria. Instead it involves moving entire nuclei or so-called “spindles” that are groupings of chromosomes, from one human egg or embryo to another.

Myth: This technology does not lead to human genetic modification. Fact: This technology conclusively does create genetically modified human embryos and hence it would produce human beings that are GMOs. Mitochondria have a genome including genes. Plants that only have a single added gene are definitively called GMO.

Myth: Mitochondria are just like little batteries that can be swapped out. Fact: Mitochondria are vital for energy production in cells, but there’s a whole lot more that they do as well. There is strong evidence that the mitochondrial genome, for example, “talks to” the nuclear genome, and has pervasive effects on cellular and organismal functioning. Therefore the notions that mitochondria are simply like replaceable batteries or that mitochondrial transfer would be just like transfusing blood into an anemic patient are misleading at best.

Myth: This technology would remove all diseased mitochondrial DNA. Fact: This technique is not perfect and it is essentially certain that at least some small amount of diseased mitochondria would remain. The consequences of the resulting heteroplasmy are reason for concern and it is possible that the diseased mitochondria might preferentially replicate, increasing their relative numbers.

Myth: Women with mitochondrial diseases have no other options for creating healthy families. Fact: There are several other options. One option is to utilize pre-implantation genetic diagnosis (PGD), which has proven potential to lead to healthy offspring and is an option for most women with mitochondrial diseases. PGD technology is only going to continue to improve as well, potentially expanding options further. Another possible option is to utilize an egg donor to be fertilized by the partner’s sperm, with the downside being that the mother to be would not be genetically related to the child produced. A third option is adoption.

Myth: This is not a new technology. Fact: While some unauthorized fertility experiments were conducted in the 1990s (eventually prohibited by the FDA) that have some resemblance to 3-person technology, they were different in important ways. For example, the technology used in the 1990s involved cytoplasm transfer between eggs rather than the more extreme intervention of nuclear or DNA transfer (as now proposed in the UK) and it did not involve mitochondrial disease. It is important to point out that even so the experiments in the 1990s led to some negative outcomes including chromosomal damage and developmental disorders.

Myth: IVF was a risky technique originally and was successful for the UK and the world so 3-person technology will do the same. Fact: While 3-person technology does involve IVF, it is a much more severe medical intervention and far riskier both to the children to be created and the country that allows the work. The pioneering work that the UK did on IVF was noble and successful, but the situation with 3-person technology is not quite analogous. The lesson from the success of IVF is not that 3-person technology will similarly prove to be safe, effective or bring honor to the UK. On all three accounts that optimistic perspective could be flat-out wrong.

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