"Children of three parents" may soon become a reality
On March 20, 2013, the British Committee on Human Fertilization and Embryology (Human Fertilization and Embryology Authority) recommended that the government of the country allow the use of new methods of in vitro fertilization, which caused a lot of controversy in the general public, developed to prevent the transmission of mitochondrial diseases to children from parents. If the government follows this recommendation, it will lead to the birth of children with genes inherited from three parents.
Let's make a reservation right away that the term that has taken root does not quite correctly reflect the essence of the method. According to Hugh Whittall, the head of the bioethics committee at Nuffield College, who analyzed the issue from an ethical point of view last year, it is "wrong, inappropriate and useless to say that children who appeared with the help of the discussed methodology will have three parents." He explains this by saying that with donor mitochondria, a child will acquire only 37 genes, whereas the number of genes he will receive from his parents will exceed 20,000. The number of genes obtained with mitochondria is negligible and cannot be compared with the number of genes obtained by a person during blood transfusion or organ transplantation.
In the UK alone, about 5,000 adults suffer from various forms of mitochondrial diseases. Mitochondria are the energy centers of a cell that have their own DNA, mutations in which can lead to mental disorders, blindness, seizures, dementia or even death. At the same time, some people have a small number of defective mitochondria, which practically does not affect their quality of life.
Defective mitochondrial DNA is transmitted from mother to child as part of the mitochondria contained in the cytoplasm of the egg. The severity of the child's disease depends on what proportion of the mitochondria of the egg contains mutant DNA. To date, women with similar pathologies have only one way out of the situation – in vitro fertilization followed by preimplantation genetic diagnosis, which allows them to choose for implantation eggs with a minimum content of mitochondria with defective DNA.
However, there are methods to guarantee the complete absence of the disease in the child. One of them was developed by Shoukhrat Mitalipov from the Oregon National Primate Research Center in Beaverton. His method involves the introduction of an egg nucleus with defective mitochondria into a donor egg, from which its own nucleus is previously removed. The second method, proposed by specialists from Newcastle University in the UK, is to transfer the nucleus of an already fertilized egg into an "empty" donor egg.
None of these technologies are approved for clinical use in either the UK or the USA. A clinical study of a similar method involving women with infertility led to a moratorium on the use of such technologies in the late 90s.
The latest recommendation to lift the moratorium is based on data obtained from the study of the safety and effectiveness of the technique, as well as the results of a recent consultation with the general public. The government is recommended to allow such manipulations, but only in clinics that have received a special license. Follow-up monitoring of the health status of children born with the help of new techniques is also recommended. At the same time, egg donors should be treated in the same way as tissue donors, that is, they should not have any rights to the child.
To date, Mitalipov's group has raised five macaques born to healthy animals as a result of artificial insemination carried out using the technique described above. Last year, scientists said they had taken the first step towards reproducing the results in a study involving humans. They removed the nuclei from 65 human eggs and replaced them with donor egg nuclei. A few days after fertilization, 48% of successfully fertilized eggs turned into full-fledged blastocysts. In 2010, Newcastle scientists demonstrated the effectiveness of their proposed technique on embryos deemed unsuitable for standard in vitro fertilization.
Both approaches still need to be optimized, since the level of successful fertilization when used does not reach 40-50%, which are considered acceptable for other types of in vitro fertilization. According to Mitalipov, he believes that he has already done everything possible in animal experiments and clinical studies are necessary to get answers to the remaining questions.
In addition to the effectiveness of the procedure, there are a number of potential problems. One of the technical nuances is that part of the defective maternal mitochondrial DNA can be transferred to the donor egg along with the nucleus. However, experiments have shown that when using both approaches, the total amount of such DNA entering the donor cell does not even reach 2%, whereas for the development of mitochondrial disease, about 60% of mitochondria must be defective. However, even single defective mitochondrial DNA can theoretically gradually "multiply" and lead to the reappearance of the disease after several generations. Therefore, the Committee on Human Fertilization and Embryology recommends conducting additional studies to study this issue.
As for the possible consequences for future generations, experts believe that, due to the limited functions of mitochondria, their risk is minimal.
Some people express concern that allowing the use of methods implying a change in mitochondrial genetic material will pave the way for approaches consisting in changing the genes contained in the nucleus.
In this regard, experts recognize the allure of the idea of preventing the occurrence of diseases transmitted to children from parents through nuclear DNA, but its exceptional complexity greatly increases the risk associated with appropriate manipulations.
Most likely, regardless of the decision taken by the UK government, the mitochondrial transfer technique will soon find clinical application in some other country in the world. According to Mitalipov, the government should realize that perseverance in this matter is pointless. He adds that if the US and the UK refuse, other countries whose governments have less prejudice will go for this.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of New Scientist: Make three-parent babies, UK government told.
22.03.2013