“Where do babies come from?” A question avoided by parents of young children for years, has now, thanks to researchers at the University of Newcastle, been given an entirely new answer.
The paper, entitled “Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease” highlights a new experimental methodology that involves the generation of what are being called “3 parent babies”. Whilst sensationally named, the protocol has potential to prevent diseases associated with mitochondria– a significant breakthrough given that all current treatment for such conditions is merely symptomatic.
Mitochondria are fascinating organelles involved in a diverse range of cellular events, the most well heard of being the conversion of energy into a chemical form usable by the cell, known as adenosine triphosphate (ATP).
What you may not know is that these organelles actually contain their own DNA distinct from nuclear DNA. This genome is tiny compared to that of the nucleus, encoding only 13 genes that are crucial for the process of ATP formation. Nevertheless, when this genome mutates it has disastrous consequences for the central nervous system and muscle tissues which are almost entirely untreatable.
This is because of a principle known as heteroplasmy. A single cell will contain thousands of mitochondria, and thus thousands of copies of the mitochondrial genome. While this may not seem like a problem, the mutation rate of the mitochondrial genome is higher than that of nuclear DNA and we as scientists have no way to manipulate mitochondrial DNA to remove these mutations. To simplify. each cell in our body has the potential to contain multiple mutated copies of the genome that we cannot treat or remove.
The elegantly simple experiment carried out at the Newcastle Institute of Ageing and Health bypasses the problem of heteroplasmy and genetic alteration altogether by cleverly avoiding the transfer of faulty mitochondria from the maternal egg to a fertilised embryo.
Reproductive cells from a woman carrying harmful mitochondrial mutations were treated with various chemicals to degrade the rigid lattice of proteins that give the cell shape; this is known as the cytoskeleton. This then allowed isolation of a pronucleus, containing half of the DNA of a normal nucleus, into small membrane vesicles called karyoplasts.
The karyoplast containing just the nuclear DNA was then inserted into a healthy fertilised zygote (a single celled embryo) containing its own complement of healthy mitochondria and the other half of the DNA required for a full genome, giving these cells all the genetic material they need to grow.
Amazingly 22% of the embryos that underwent pronuclear transfer grew to form embryos of greater than 8 cells (called a blastocyst), while this may seem tiny, forming viable cells is a huge leap, especially considering that the embryos being used in the experiment were “abnormally fertilised” and therefore less likely to survive and grow than if this technique was applied to normal cells, however far in the future.
But the good news doesn’t end there. By identifying patterns in mitochondrial DNA specific to these organelles, the amount of harmful mitochondria that transferred within the karyoplast was measured and found to be less than 2% of the total mitochondrial DNA, an excellent result given that >60% level is required for mitochondrial disease to occur.
This in essence means that harmful genetic mitochondrial mutations can be left behind while the DNA of the mother is transferred to a new healthy fertilised zygote sourced from another egg cell.
This is where the 3 parents issue arises, as many people will misunderstand and assume scientists have somehow warped the process of conception.
The truth, however, is much simpler and much less daunting. The term “parents” refers the amount of DNA donors, and while technically true, the 3rd parent in pro-nuclear transfer provides only mitochondria (and its associated genome). As mentioned previously, this genome is tiny and represents approximately 0.043% of the total genes expressed in an individual, and is involved almost exclusively in ATP production. Its role in forming phenotype – essentially what makes you, you – is less than negligible.
I should mention, I’m not ignoring the ethical and social implications of a child with 3 parents, as these clearly need to be considered. Treatment, however far down the line, will always be a choice for the parents in that respect, and should in my opinion be left as such.
The potential for misunderstanding and lobbying against this treatment is high but is by far out-shone by the potential for treating a class of disease that until recently has seemed unbeatable.
Craven L, Tuppen HA, Greggains GD, Harbottle SJ, Murphy JL, Cree LM, Murdoch AP, Chinnery PF, Taylor RW, Lightowlers RN, Herbert M, & Turnbull DM (2010). Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature, 465 (7294), 82-5 PMID: 20393463