Mitochondrial Donors in IVF

I want to revisit the article I posted about "three-parent babies." It's vaguely related to my research, but also I just find it plain fascinating (I do, after all, have something of a bias for mitochondrial research.)

The article describes a new technology that would allow people with mitochondrial diseases to avoid passing it on to their children. This technology involves the use of a mitochondrial donor for in-vitro fertilization. Let me start by explaining how this works.

Mitochondria have their own DNA, separate from the nuclear genome. When you think about your genes, you traditionally picture your 46 chromosomes, housed in the nucleus. You get half of it from your mother, half from your father. The mitochondrial genome is different in many respects, but for my purposes right now, I'll say just this: it's entirely maternally inherited. You don't have any mtDNA from your father, at all.

This means that if your mother carries genes for a mitochondrial disorder, you have a 100% chance of inheriting it. If your father has it, you have a 0% chance.

This is where IVF comes in. In mitochondrial research there is a technique called cybridization. This is a process where you take the nucleus from one cell and the mitochondria from another cell and combine them for a "cybrid" (cytoplasmic hybrid) cell containing two different sets of DNA. This is something that my lab does routinely, and it's great for screening for the effects of mitochondrial mutations without any "background" nuclear mutations confounding your results.

Image from nydailynews.com

In this context, rather than eliminating confounding variables, cybridization would eliminate the disease genes by using a mitochondrial donor. So, in essence, the IVF would go like this: take sperm and egg from the couple seeking IVF, and another egg from a mitochondrial donor. Fertilize the mother-to-be's egg with the sperm, then remove the nucleus from the now fertilized embryo, and move it over to the mitochondrial donor's egg (removing the donor egg's nucleus first). In this manner, you have now created an embryo with nuclear DNA from the two parents-to-be, and mitochondrial DNA from a third donor.

What this means for women with a family history of mitochondrial disease is that there is some hope that they will not have to pass on that disease to their children. While these diseases are rare, they are often severe, and it can be devastating to people trying to start a family. But this therapy has broader implications scientifically, socially and ethically.

On one level, the idea of the "three-parent baby" is completely accurate, but at the same time it is extremely misleading. All of your physical traits are encoded in the nuclear genome. Everything that makes you your parents' child is there. The nuclear genome encodes for something on the order of 30,000 proteins, while the mitochondrial genome encodes for 14. Why, then, can a mutation there have such a profound impact on a person's health? Well, those 14 proteins are very important. They make all the energy your cells need to run. Without them, your body shuts down. But again: they don't have anything to do with your physical characteristics.

Image from Nature.com

One thing that would absolutely change, and this is something I find fascinating, is your haplogroup. Haplogroups are genetic categories that define where your ancestors came from. They trace migration patterns of early humans all the way back to the original Homo Sapiens that lived in Africa. The DNA that is used to determine your haplogroup is mitochondrial DNA, entirely. All of human migration patterns are traced through maternal lineage, and the fastest way to do that is by looking at the mitochondria. At the moment, this is a useful technique: mitochondria are maternally inherited, so it's safe to assume that your mitochondrial DNA reflects your maternal lineage. But once this technology becomes available, there will suddenly be a small portion of the population for which this assumption is not true. Their mtDNA would reflect the haplogroup of the mitochondrial donor, not their mother.

I think another issue that the idea of the "three-parent baby" brings up, which is something of a red herring, is that suddenly we will have groups of three people caring for and being responsible for children. I don't think this will happen. Just as sperm donors are not held to any kind of parental responsibility, a mitochondrial donor would be free of any obligation. Does this raise ethical problems for custody, parental status, etc.etc.? No, I don't think so. Instead of trying to shoe-horn a completely new technology into existing definitions, I think it would be simpler and more accurate to adjust our ideas about what assumptions we make about someone's DNA, and what it means for their personal identity. A child who had a mitochondrial donor is just that; their parents are still their two (nuclear) parents. But, and I'm sure this is predictable coming from me, it's still really, really cool.