Mitochondria are the powerhouses of the cell; their function is to produce energy. (See the orange-colored structures in the figure.) These tiny cellular organs also contain a trace amount of DNA (mitochondrial DNA or mtDNA), which encodes various enzymes used in energy production and RNA molecules for protein synthesis.
Since sperm do not contribute any mitochondria to a fertilized egg, all of the mitochondria a cell contains came from the mother. Also, because mitochondria contain DNA, they are susceptible to mutations, and hence, genetic disease. Mitochondrial diseases tend to affect cells which use a lot of energy, such as muscles and neurons, and the severity of the disease depends on the type of mutation and the number of mitochondria affected.
If a woman has a mitochondrial disease, she will almost certainly pass it on to her children. But, scientists at the Oregon Health & Science University have shown that a gene therapy technique may be able to prevent the transmission of mitochondrial disease.
Researchers acquired eggs from healthy human donors and then performed reciprocal "spindle transfer." This means they swapped the egg's nuclei (the structures which contain most of a cell's DNA -- the purple blob in the picture). In other words, the nucleus of Egg #1 was transferred to Egg #2, and the nucleus from Egg #2 was transferred to Egg #1. (Note that the mitochondria were left behind.) Following that, the cells were fertilized with sperm and their fate was monitored.
Out of 64 fertilized eggs, 19 developed into blastocysts (early-stage embryos). The researchers were able to derive embryonic stem cells from some of these blastocysts.
Also, the researchers followed up on a previous experiment in which they produced monkey offspring using this "spindle transfer" procedure. The monkeys were completely healthy.
This study is what is known as a "proof-of-concept." Although the researchers used healthy human eggs and monkeys, they showed that it is theoretically possible to transfer a nucleus out of an egg with mutated mitochondria into a new egg that contains healthy mitochondria. From there, fertilization can yield a healthy blastocyst, which can then be implanted into the uterus to produce a healthy baby.
Although this technique shouldn't be controversial, it almost certainly will be. The resulting blastocysts have already been called "three parent embryos," much to the chagrin of scientists. While this is technically true, it should be pointed out that the DNA from the "third parent" (which comes from the healthy mitochondria) is miniscule (around 16k DNA base pairs) compared to the much larger amount of DNA contained in the nucleus (6 billion DNA base pairs in the diploid genome).
This technique, once perfected, will prevent genetic disease being transmitted via mitochondrial DNA. However, it may also keep bioethicists and lawyers busy for a long time.
Source: Masahito Tachibana et al. "Towards germline gene therapy of inherited mitochondrial diseases." Nature 490 (7421). 2012. doi:10.1038/nature11647
(Image: Typical animal cell via Shutterstock)
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