The first "child from three parents"

Mitochondrial donation: the first steps

Maxim Russo, Polit.roo

New Scientist magazine reported the birth of a child who was conceived using mitochondrial donation technology. This method, which avoids a number of hereditary diseases, has been at the center of a heated discussion since 2014, especially aggravated when the permission of mitochondrial donation was discussed in the UK Parliament. In the press, this medical technology is often called the birth of a child "from three parents."

Mitochondria are cellular organs engaged in converting incoming nutrients into ATP molecules, which serve as a universal energy reserve for all processes in the body. Mitochondria have their own DNA with 37 genes, and some of the genes that determine the work of mitochondria have been transferred to the nuclear genome. The child inherits mitochondria from the mother.

A number of mutations occurring in these 37 mitochondrial DNA genes lead to the appearance of mitochondrial diseases. Normally abnormally functioning mitochondria produce free radicals that damage the cell, disrupt a number of important processes and accelerate cell aging. In mitochondrial diseases, mitochondria with both normal and defective genomes (the so-called heteroplasmia) are often present in cells, so for a while normal mitochondria satisfy the needs of the body, but sooner or later the number of mutated mitochondria increases so much that they begin to affect the body.

Mitochondrial diseases are characterized by myopathy, hypotension, low exercise tolerance, cardiac arrhythmias, optic nerve atrophy, disorders of peristalsis and the work of the endocrine glands. The frequency of hereditary diseases associated with mutations in mitochondrial DNA is 1 per 5,000 newborns. Treatment of mitochondrial diseases is currently known only symptomatic, it is impossible to rid the patient of his pathology.

Mitochondrial donation uses a woman's egg that does not contain defective mitochondria. In such an egg, a nucleus is transplanted from the egg of another woman who wants to become a mother, but cannot because of mutations in mitochondrial DNA, or who has a high probability that the child will be seriously ill. After that, the egg is fertilized by the sperm of the future father and implanted into the uterus, as with conventional in vitro fertilization.

Initially, doctors did not want to resort to donating a whole egg and tried to do with a partial measure, when cytoplasm from the egg of a healthy woman with mitochondria was injected together with sperm into the egg of a woman with a mutation in mitochondrial DNA. But such experiments conducted in the 1990s were only partially successful. In early February 2015, mitochondrial donation was allowed in the UK.

However, the case of the birth of a child with donor mitochondria described by New Scientist magazine did not occur in the UK, but in Mexico. The egg nucleus was transplanted and fertilized by doctors from the United States, in whose homeland such manipulation is not yet allowed.

A married couple from Jordan, who decided to resort to the help of doctors, tried to give birth to a child for 20 years. Two of their children died at an early age from a genetic disease – Ley syndrome, four more pregnancies ended in the death of the embryo.

With Ley syndrome, a violation of energy metabolism in the body leads to the appearance of foci of necrosis in the brain stem and cerebellum, as well as to the replacement of dead nerve cells with neuroglia. Patients develop weakness, nausea, hypotension, tremor in the extremities, impaired coordination of movements, optic nerve atrophy and other signs of damage to the nervous system. The disease progresses rapidly. Within a couple of years after the onset of the disease, death occurs from paralysis of the respiratory center of the brain. Most often, the disease manifests itself in children from the moment of birth to three years. The cause of the disease is a mutation in mitochondrial DNA.

The boy, who received not maternal mitochondria with defective DNA, but the mitochondria of a female donor, was born in Mexico on April 6 this year. The doctors decided to notify the general public about his birth only now, when it became clear that Ley syndrome did not threaten him.

Dr. John Zhang and his colleagues who performed the donation procedure examined the mitochondria of the child and found that no more than 1% of them contain defective DNA. Doctors believe that this is not enough for the manifestation of Ley syndrome. According to previous studies, the disease develops when the number of mitochondria with defective DNA reaches 18%.

There is one difference between the mitochondrial donation technique allowed in the UK and the manipulation carried out in Mexico. In the variant offered by British doctors, the eggs of the mother and the donor woman are fertilized in vitro by the father's sperm. And then, before the first division of the fertilized cells, the nucleus from the mother's egg is transferred to the egg of the donor woman, whose own nucleus is removed. The Jordanian couple refused this option for religious reasons. They considered that an embryo that had already appeared was dying in it. In Mexico, the variant of mitochondrial donation described above was used, when first the nucleus from the mother's cell is transferred to the donor egg, and only then fertilization is performed.

Portal "Eternal youth" http://vechnayamolodost.ru  28.09.2016