This week’s paper describes a new technique that could be used to manipulate human oocytes (i.e. eggs) to prevent a group of diseases called mitochondrial diseases. The paper was presented by Tachibana et al. in Nature along with a similar paper by Paull et al. For the sake of brevity, I will only discuss the findings from the first paper.
So what are mitochondria? Mitochondria are little compartments in the cell that make cellular energy. They convert the energy stored in food into an energy source that the cell can use to drive chemical reactions. In other words, they are absolutely essential for our survival. The oxygen that we breathe in goes to the mitochondria to aid in this energy conversion, and we all know how vital oxygen is.
There are two other interesting facts about mitochondria that relate to our story:
1) All the mitochondria in our body are duplicates of the mitochondria that were in our mother’s egg. In other words, embryonic mitochondria are not made from our genomic DNA (gDNA) or from sperm contributions.
2) Mitochondria have their own DNA , which directs the synthesis of proteins that are necessary for their function. This DNA is known as mitochondrial DNA (mtDNA) and it is only inherited from the mother, since all mitochondria originate from the egg.
If there are mutations in the mtDNA, then this can lead to problems with the synthesis of cellular energy, which can lead to human diseases known as mitochondrial diseases. There are different types of mutations, which can affect people in different ways and with differing severities. In this paper, the authors propose a way to prevent mitochondrial diseases from being inherited from generation to generation. Let’s see how that works.
Let’s say you have a female patient with a mitochondrial disease, who wants to have a healthy child. She is guaranteed to pass this disease on to her child via the mitochondria in her oocytes. However, most of what makes the child “hers” is what lies in the mother’s genomic DNA, not in the mitochondrial DNA. What if you could take the mother’s genomic DNA (plus the DNA from the father) and stick it into a healthy “enucleated” oocyte from a donor who has good, functioning mitochondria? All the genomic DNA will have to be cleared out of the donated oocyte first, creating an enucleated egg. The embryo that results from this nuclear transplantation will have genomic DNA from its mother and father, but its mitochondria will originate from the donor oocyte. This would circumvent the mutated mtDNA that is in the real mother’s oocyte.
Tachibana et al. obtained human oocytes from volunteers and transfered the genomic DNA from one into another. They then injected these oocytes with sperm DNA (like during real fertilization) and observed what happened. Some oocytes failed to be fertilized and others died soon after, but a handful of oocytes survived into the blastula stage of development. You can’t really grow a human embryo in a dish beyond the blastula stage and they are not allowed (yet) to implant these into women, so we don’t know what would happen to a child born from this procedure.
They did carry out the above scenario with monkeys. They transplanted the genomic DNA from one oocyte into another and implanted the blastula into another female monkey who carried the embryo to term. The monkey youths are 3 years old now and doing just fine. Their maternal genomic DNA is from one mother and their mitochondria are from a different oocyte donor.
Isn’t this amazing? I seriously doubt this procedure will be approved for human use anytime soon, because it’s too much like cloning, which basically follows the same procedure of putting genomic DNA into an enucleated egg. It's a cool idea, though.