The UK parliamentarians voted, Tuesday, February 3, in favor of medically assisted procreation project intended to prevent the transmission of genetic diseases of maternal origin. Colloquially called IVF "three parents", she is to replace in the bud small structures called mitochondria, present in all cells in which they provide the energy they need. Some diseases are indeed linked to mutations in mitochondrial DNA. All embryo mitochondria are maternally derived.
• What are mitochondrial diseases?
Constituting power plants for the synthesis of proteins and other molecules, mitochondria are structures found in cells, outside the nucleus, in the cytoplasm. They have their own DNA, always inherited from the mother. The mutations of the mitochondrial DNA (mtDNA) are responsible for a set of more than 700 non-treatable metabolic diseases to date and some potentially fatal in childhood. They can manifest themselves neurologically, neuromuscular, ophthalmic disorders (optic neuropathy Leiber), anemia, deafness ...
According to the British Office of the Human Fertilisation and Embryology (HFEA), about one birth in 5000, and probably a higher proportion of fetus has a mutation in mtDNA. Also according to the HFEA, it is possible to have recourse to pre-implantation diagnosis, selecting embryos with only very few mtDNA mutations, but this provided he has previously identified the mutation in question.
• What is the mitochondria replacement technique?
If the problem is related to mitochondria, have said British researchers from the University of Newcastle, replace them rather than using a conventional oocyte donation from a donor. The idea was to preserve the mother's genetic heritage, carried by the chromosomes found in the cell nucleus. For this, the researchers used the technique of nuclear transfer.
The process consists of an egg from the mother, so mitochondrial carriers containing the offending mutation. The oocyte is fertilized by a sperm father, and then, the resulting egg's nucleus is removed. An egg from a donor, disease-free, has also been fertilized before being stripped of its nucleus. The core comprising from genetic heritage of maternal origin is then transferred into the egg from the donor.
The resultant egg therefore has a core concealing the genetic heritage of the mother and father, whose cytoplasm and mitochondria contain DNA from the donor free of mutations. So three DNA, one of the donor being ultra-minority.
Another technique exists, where the transfer is made from oocytes, one maternal and one of the donor, the egg is then fertilized resulting in a paternal sperm.
In the US, an application for authorization of a clinical trial using this technique was submitted in February to the US Food and Drug Administration. The FDA has not yet rendered a decision.
• A safe technique?
In a statement of 22 July 2014, announcing the government bill authorizing the use of mitochondrial replacement technique, the HFEA said its expert panel, chaired by Dr Andy Greenfield, had clearly indicated in its report of June in 2014 he "had found no evidence suggesting that the mitochondrial replacement is not sure and that good progress had been made scientifically. "Studying the animal and human data over several years, the panel took into account the safety aspects related to the transfer itself, reagents used for this technique and the interactions between the nucleus and the mitochondria.
On this occasion, Dr. Greenfield said: "Getting from research to clinical practice always involves a degree of uncertainty. If parliament actually changes the law, the regulatory procedure required by the HFEA before treatment is proposed guarantee, as much as possible to do the replacement of the mitochondria works and is safe enough to be offered to people with severe mitochondrial diseases. "
• What are the ethical issues raised?
Although the British Parliament has adopted the amendment to the 2008 law on medically assisted procreation to allow overwriting of mitochondria, the technique will not be provided immediately proposed. Like any technology at the cutting edge of science, it must be supervised by the HFEA regulations must develop. The regulatory authority must design and implement a process, including defining a specification for institutions would be allowed to practice it.
Ethical issues are also raised about this new technique. Firstly, that it causes a change in the so called germline, ie cells involved in fertilization (as opposed to the somatic lineage that gives the other cells of the body). Therefore, this means that mtDNA from the donor will be transmitted to progeny in addition to that of the two parents.
From this point of view, there may be a difference between the two techniques. In that where the transfer occurs after fertilization, the embryo of the future genetic identity will have been established by the paternal and maternal chromosomes before treatment. In that the transfer is performed on oocyte before fertilization, the mitochondrial DNA of the donor and the individual preexists created will be different from what it would have been with only two parents.
Earnings - non-transmission of the mutation - is obvious, but it can raise questions. In particular the anonymity or not mitochondria donation (the gamete donation is not anonymous). At the World Congress of Bioethics, June 25, 2014 in Mexico City, Dr. John Appleby, of the ethics center and medical law at King's College (London), referred to the fact that the mitochondria of donation is not likely influence significantly on the identity and the physical traits of the descendants, which would therefore be reticent to inquire about the identity of the donor mitochondria. But on the other hand, why deny access to such information, he asked.
Of eugenics charges have also been advanced as in other techniques to avoid the birth of children carriers of serious diseases. But in the case of replacement of mitochondria by nuclear transfer, there is no selection of embryos, with the elimination of those carriers of the mutation of the mtDNA.
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