In April last year, the world's first child was born, conceived by three parents. His cells contain DNA from three people - two women and one man. But not so long ago, an article appeared, in which the procedure performed the year before last was described in detail, and its possible consequences were described. This experiment, it is worth noting, caused serious controversy in the scientific community.
The boy was born as a result of the work and great efforts of doctors at the New Hope Fertility Center (New York). They underwent mitochondrial replacement therapy, which is also known as the “three-parenting method.” In this way, doctors helped a couple from Jordan, whose two children had previously died at an early age (from eight months to 6 years) as a result of Leigh's syndrome - a dangerous genetic disease.
Subacute necrotizing encephalomyopathy or Leigh syndrome is an incurable disease that affects the central nervous system. As a rule, the first symptoms begin to appear in one-year-old children and are expressed in vomiting, diarrhea, dysfunction of swallowing, as a result of which the child quickly loses weight. As the disease progresses, the work of muscles (in particular, of the eye) is disrupted, because the brain is deprived of the ability to control the process of their contraction. The most common cause of death is respiratory failure.
Leigh syndrome occurs as a result of mutations in genes that are associated with the work of mitochondria. Many of them are contained in the mitochondrial genome, despite the fact that more than three dozen nuclear genes have been described in science, which may also be involved in the development of the disease. About a quarter of all known cases of the disease are associated with mutations that develop in mitochondrial DNA. These mutations can provoke disruptions in the work of ATPase, an enzyme that catalyzes the breakdown of the ATP molecule and releases energy that is used by many vital processes in the body.
Very often it happens that defective (without normal ATPase) and normal mitochondria coexist in the same cell - this condition is called heteroplasmy. Symptoms of the disease appear depending on the number of defective mitochondria, which determines the mutational load.
According to research, Leigh's syndrome is most likely to appear when the level of hereroplasmia reaches 6070 percent. A Jordanian woman who went to a New York center for help had a mutation load of 24.5 percent. Thus, she was only carriers of "damaged" mitochondria, but she herself did not suffer from the disease. At the same time, in two of her dead children, the level of heteroplasmy reached 95 percent. To protect the unborn child from this genetic disease, doctors decided to resort to a desperate step: to replace all possible mitochondria in her egg that could be passed on to her child.
When information appeared about the birth of a child, scientists criticized the experiment, although they recognized its enormous importance. At that time, the details of the experiment were very little known, so many scientists expected explanations from the authors of the experiment.
In early April, an article appeared in one of the specialized publications, in which doctors spoke in detail about the methods that were used in the process of creating an embryo.
Promotional video:
The experiment was led by US surgeon John Zhang. The ovarian stimulation procedure and oocyte collection were performed at the Fertility Center. In the same way, all the necessary manipulations with biological material were carried out there. Scientists acted with a laser beam on a section of the mother's egg membrane, thanks to which they managed to accurately insert a microinjection pipette and remove the nucleus. The nucleus was surrounded by a membrane, it was fused with a donor healthy egg. For this purpose, the electrofusion method was applied, during which the cells were exposed to small electrical impulses.
The resulting egg was fertilized with the father's sperm, after which the resulting embryo was frozen and transported to Mexico, to an affiliated clinic. It was there that the operation was carried out to implant a fertilized egg into the uterus, because American law prohibits the use of this technique for conception. The baby was born at the 37th week.
Some experts reacted favorably to the publication. So, in particular, according to the American researcher of stem cells Dietrich Egli, this study is a historical scientific work.
At the same time, the experimenters themselves admitted that some of the defective DNA from the mother was randomly transferred to the donor cell. According to scientists, this can provoke unpredictable consequences for the child's body, because some of the mitochondria in its cells will not work normally. The number of defective mitochondria differs among tissues. Only two percent of the mother's mitochondrial DNA was detected in the urine sediment; nine percent was already detected in the cells of the foreskin. At the same time, it is impossible to determine how much of it is contained in the cells of the brain or heart without surgical intervention. It is likely that the mutational load in these tissues may be much greater. However, in general, scientists assess the child's chances of living a healthy life very positively.
As Egli points out, human experimentation can help researchers learn something completely new. However, in this case, we are not talking about an already born child, since his parents refused any further research, unless there is an urgent medical need. In addition, Zhang did not answer a question from reporters whether his colleagues secured parental consent to conduct long-term medical monitoring.
If scientists are prevented from observing the development of a unique patient, the value of their work will be greatly reduced. Scientists believe that it is too early to apply such a technique for treatment, since it is not known what the long-term consequences may be for children born in this way.