Mitochondrial Donation: The Animal Research that Paved the Way
Earlier this month Britain become the first country in the world to permit mitochondrial donation to be used in treatment and help prevent serious genetic diseases. The procedure, which allows IVF babies to be created using donor mitochondrial DNA, has the potential to help some 2,500 mother in the UK alone. Many are not only concerned with the ethics, but on how safe the procedure actually is. Previous research has used mice and rhesus monkeys, but are these animals a good indicator of human reproductive biology?
Mitochondria are small structures inside our cells that generate the energy needed. It’s important to note that mitochondrial DNA, which contains 37 genes that control the function and energy production, is different from nuclear DNA—a genetic database that determines physical appearance and some personality traits.
While mitochondrial DNA tends to be more stable than nuclear DNA, mutations can still occur. These mutations can lead to mitochondria disease. The disease manifestation can range from blindness, seizures, dementia, to early death. It can affect multiple organs, and there are currently no cures. As mitochondrial DNA is passed down from mother to child, women can choose to receive an entire donor egg, which results in having a child who is not genetically related to them, or screen their eggs for ones with low proportion of mutant mitochondrial DNA.
Jun-Ichi Hayashi, Professor of Biological Sciences at University of Tsukuba, looked into the practicality of screening for mitochondrial mutations. He found that mice with a mitochondrial mutation rate of 40% or less did not express any abnormal symptoms throughout their lifetimes. He told EARA:
“We used mice as they’re a good model for mitochondrial disease. In fact, most researchers in the world use mice as models for various human diseases,”
Unfortunately, pre-screening isn’t available to everyone. Some women either have a high proportion of abnormal mitochondrial DNA or all is abnormal and thus aren’t able to use their eggs. For these women, mitochondrial donation offers an alternative.
There are currently two IVF techniques, the first being maternal spindle transfer (MST); where the nuclear DNA is removed from the mothers egg—that contains mutated mitochondrial DNA—and is inserted and replaces the nucleus of a donor egg with healthy mitochondria. This technique differs slightly from the second as the egg is not fertilised and there is no embryo.
Research on rhesus macaques paved the way for MST to be used for clinical use.
Dr Shoukhrat Mitalipov and his research team at the Oregon National Primate Research Center were able to create three healthy baby macaques using the MST technique. Mitalipov reported that the baby macaques were developing normally after 3 years. The researchers then went on to create healthy human embryos using the MST technique.
The second proposed treatment—pro-nuclear transfer (PNT)—occurs post conception with two fertilised embryos, one from the parents, and the second from donor embryo. The pronuclei in the donor embryo is replaced with the pronuclei of the parental embryo.
Hayashi, who pioneered PNT research in mice, says:
“the procedure carries the technical risk of inducing nuclear abnormalities and prompts ethical concerns regarding the production of three- parent babies with normal mtDNA from unrelated oocyte donors.”
Though it’s been reported that the procedure will lead to ‘three parent babies’ the baby would only have 0.1% of a donor woman’s DNA, and 99.9% of its parents DNA. After three separate reviews by Human Fertilisation and Embryology Authority’s (HFEA) specially convened Expert Scientific Review panel, there was no evidence to suggest that mitochondrial donation was unsafe for clinical use. According to the Wellcome Trust, the procedures underwent the most thorough investigation before it was approved.
30 years of animal research has resulted in the development of these mitochondrial donation techniques, which will be trialled now in clinics. From the first studies in the mid-1980s on PNT in mice to MST research on rhesus macaque monkeys, animals have paved the way to help many families to conceive healthy babies.
The procedure, which might be covered by the UK National Health System, will have to be coupled with counselling services—so parents are aware of risks as well as the benefits—and children born this way will be followed up. Let’s hope other European countries provide parents with the same opportunity to raise their children without the devastating effects of mitochondrial disease.