Three in a boat

On the legalization of mitochondrial replacement

Danila Bredikhin, "Biomolecule"

Recently, there was hope that children in the United Kingdom will be able to have three parents: members of the House of Commons of the UK Parliament voted to legalize the procedure for replacing mitochondria. The idea of the approved technology is in vitro fertilization, which involves material from three different donors, which prevents the transmission of hereditary mitochondrial diseases from mother to child.

Mitochondrial DNA and its "breakdowns" As you know, mitochondria – the organelles responsible for the energy supply of the cell – carry their own genetic information recorded in mitochondrial DNA (mtDNA).

(Despite the long co-evolution, this molecule is still a bit of a stranger to our body: "Mitochondrial DNA as an immunogen" [2]. She never even learned how to read and copy "humanly": "The switch of transcription and replication processes in mitochondria has been investigated" [3] – Ed.)

The number of genes in mtDNA is usually much smaller than in the "main" DNA of the cell. Thus, in humans, mtDNA contains sequences of 37 genes, of which 13 are protein-coding (the remaining sequences encode ribosomal and transport RNAs) [1].

Of course, like any other, mitochondrial DNA is subject to the accumulation of mutations, which can eventually lead to serious diseases. As a rule, first of all, the functions of the tissues that consume the greatest amount of energy – the brain, heart, muscles - are disrupted. Barth syndrome, Ley syndrome, mitochondrial encephalomyopathy, and special myoclonic epilepsy are only a small part of a long list of diseases caused by mitochondrial damage [4].

During fertilization, it is the maternal mitochondria (egg mitochondria) that are transferred to the individuals of the next generation. This means that the mutations accumulated in the mother's mtDNA will be transferred to the child. It is estimated that 1 in 5,000 children are born with diseases caused by such mutations [5]. And very often the "family boats" are broken about the hardest life associated with the upbringing of a sick child.

Mitochondrial replacement: destroying the disease in the bud It is possible to prevent the inheritance of destructive mutations with the help of an uncomplicated – in words – procedure, which is based on the use of mitochondria from the "third parent".

Of course, this can only be done during in vitro fertilization (IVF) [6]. First, two sets of cells are prepared: the mother's eggs containing defective mitochondria, and the donor woman's eggs with mitochondria whose DNA does not carry dangerous mutations. The researchers then extract the nuclei of the maternal eggs and replace them with the nuclei of the mtDNA donor eggs. An alternative method is the transplantation of pronuclei – male and female – from a fertilized egg. Both genomic transplantation technologies are presented in the form of infographics (from [5], adapted for the Russian-speaking audience).

Final wordOn January 28, 2015, a letter from researchers from Newcastle University was published in The New England Journal of Medicine, in which the authors noted that the mitochondrial replacement procedure could help more than two thousand British women – according to scientists, that is how many representatives of the fair sex in the United Kingdom carry dangerous mtDNA mutations [7].

The decision taken can undoubtedly be considered a triumph of scientists, because it was possible to change the law allowing experiments on genomic transplantation exclusively for research purposes.

However, an unconditional victory is still far away: the House of Lords will have to make its decision on the issue of legalizing the use of technology in clinical practice. If the law is approved by the House of Lords, it will enter into force only in October of this year. Moreover, clinics wishing to provide the type of gene therapy under discussion will need to obtain special permission from the UK Human Fertilization and Embryology Authority (HFEA). And yet it is likely that the path of the new technology to the clinic and public recognition will not be as thorny as it happened with the IVF method, the developers of which have been fighting off "God-worshippers" for decades [6].

The researchers hope that the decision adopted by the House of Commons of the UK Parliament will serve as an impetus for the adoption of similar decisions by governments of other countries.

LiteratureLarsson N. and Clayton D.A. (1995).

1. Molecular genetic aspects of human mitochondrial disorders. Annu. Rev. Genet. 29, 151–178;
2. Biomolecule: "Mitochondrial DNA as an immunogen";
3. Biomolecule: "The switch of transcription and replication processes in mitochondria has been investigated";
4. Stockton N. How It’s Possible for a Baby to Have Three Parents. Wired. 04-02-2015;
5. Callaway E. Scientists cheer vote to allow three-person embryos. Nature News. 03-02-2015;
6. Biomolecule: ""For in vitro fertilization" is not a toast, but a Nobel Prize!";
7. Gorman G.S., Grady J.P., Ng Yi, Schaefer A.M., McNally R.J., Chinnery P.F. et al. (2015). Mitochondrial donation – how many women could benefit? N. Engl. J. Med. doi: 10.1056/NEJMc1500960.

Portal "Eternal youth" http://vechnayamolodost.ru12.02.2015