Genetics suggests, and epigenetics disposes
Leading specialist of the University of Geneva Ariane Giacobino
about why genetics turned out to be wrong
Recently, the journal Translational Psychiatry published the results of his new study on the direct link between violence, physical and mental injuries and mutations at the gene level. And the journal Science is about the influence of epigenetic processes on male infertility. The lead author of these studies is Professor Ariane Giacobino. With her, "VD" talked about how the world around us changes a person from the inside.
"VD" In the scientific world, many are skeptical about epigenetics.
A.D. is a young science, and many processes within the framework of epigenetics either diverge from generally accepted theories, or they do not lend themselves to reasonable explanation at all. The most famous example in this regard is the vole mice, which are born with longer and thicker fur before the winter cold than in spring, although the intrauterine development of spring and autumn rodents takes place in the same conditions. Studies have shown that the signal triggering epigenetic changes (an increase in the length of the coat) is a change in the level of melatonin concentration in the blood: in spring it gradually decreases, and in autumn it increases. It turns out that adaptive changes occur even before the onset of cold weather. But exactly how such an epigenetic process occurs is unclear. From the outside, it looks as if the cells of the body have a consciousness that controls the mechanisms of adaptation.
"VD" So what is the difference between epigenetics and traditional genetics?
A.D. The classical genetic model says that a person receives genes from his mother and father, and they inherit them from their parents. These genes remain virtually identical from generation to generation, with the exception of random mutations. Epigenetic inheritance, on the other hand, suggests that human experience leads to directed molecular changes at the top of genes. And these molecular changes can, in turn, be transmitted further, affect children and grandchildren. As the English biologist, Nobel Prize winner Peter Medavar said, genetics suggests, and epigenetics disposes. Epigenetics has become the link between the outside world and genes that scientists have been looking for for so long. She finally put all the dots over the "I" in more than a century of discussion about sociogenetism and biogenetism. The question of whether we inherit all the properties or can acquire them under the influence of upbringing, culture and interaction with the external environment is no longer worth it.
"VD" By the way, it turns out that environmental pollution is also reflected at the genetic level?
A.D. Gene expression (the process by which hereditary information from a gene, a sequence of DNA nucleotides, is converted into a functional product – RNA or protein) is influenced by a variety of chemical compounds, such as pesticides, waste incineration by-products, primarily dioxin. The real scourge of the modern world is bisphenol A, which is present in any plastic products. Moreover, over the years, people become less adaptive to environmental conditions. This means that with each generation, humanity is becoming more vulnerable.
Today it is almost impossible to find a person whose body did not contain bisphenol A: it is in the blood, breast milk and umbilical cord blood of pregnant women. Any food contact with cans and plastic, even with bottled drinking water, adds a portion of bisphenol to the body. At the same time, the ability of this chemical to inhibit the maturation of the egg and thereby provoke infertility, the ability to erase the differences between the sexes and stimulate the birth of offspring with homosexual tendencies has already been established. Moreover, even small doses of bisphenol A cause persistent disorders in the brain, which may erase differences in the behavior of representatives of different sexes.
"VD" And how do pesticides affect a person?
A.D. We studied the effects of pesticides on the formation of the fetus during pregnancy, as well as how this subsequently affects the adult body. Our latest study showed that pregnant female animals, which were fed pesticides so beloved by farmers around the world, had male offspring with a sharply reduced number of sperm cells or infertile at all. The pathological effects of pesticides have been manifested for four generations. Chemicals have the same effect on people.
"VD" One of your recent studies suggests that childhood resentments are imprinted on the genes?
Indeed, the insults received in childhood not only remain in the memory and subconscious of an adult for a long time, but can also have a serious impact on his genes and cell phenotype. In this case, we observed the transformations of the NR3C1 gene, which plays an important role in the physiological response of the body to stress (affects the hypothalamic, pituitary and adrenal functions). Mutations of this gene can lead to the development of various psychopathologies, such as personality change, known as "borderline state". The study involved 200 patients who were either already depressed or approaching the "borderline state" between neurosis and psychosis. In those of them who became victims of violence in childhood, methylation (modification of the DNA molecule) of genes was more pronounced. The results of the study made it possible for the first time to establish a link between childhood maltreatment, gene methylation, mental dysfunction and, as a consequence, the appearance of a mental disorder.
"VD" But if epigenetics says that upbringing and lifestyle are reflected at the genetic level, then can the person himself correct the inherited negative epigenetic mutations?
A.D. The more research is carried out in this area, the more obvious it is that fate is shaped mostly by the behavior of the person himself. This is also confirmed by the fact that over the course of life, twins have pronounced external differences. Twin brothers and sisters, initially similar in appearance and having an identical genetic code, have a different epigenetic profile, which is formed under the influence of an individually lived life. With age, DNA methylation increases, which explains the different facial features, different complexion, which can be observed in adult twins. Moreover, it is noted that these differences are greater the greater the distance between their places of residence, that is, the more their living conditions differ.
"VD" It turns out that by changing habits, we change our destiny?
A.D. You can change everything: your constitution, your metabolism, your personality. Unlike relatively stable genetic information, epigenetic "tags" can be reversible under certain conditions. Contrary to the claims of biofatalists, our life is not completely predetermined by heredity. Yes, there is a biological destiny, a genetic program that controls the body and psyche, but to a large extent it is all in our hands. A change in lifestyle becomes the beginning of biochemical transformations that radically change both a person and his descendants.
"VD" Well, for the lazy, is it possible to improve yourself by contacting doctors?
A.D. This sphere has very great prospects, but it is just beginning to develop. Usually epigenome editing strategies involve the use of CRISPR or TALE systems. Both of them consist of components of bacterial cells and can be programmed to deliver an epigenome-modifying enzyme to certain genes. An enzyme such as DNA methyltransferase is used to inactivate the target gene. On the other hand, the target gene can be activated by delivering histone acetyltransferase to it. Optoepigenetics is actively developing, with the help of which epigenetic changes can be made. The light-activated protein cryptochrome-2 (Cry2) is used for this. Under the influence of light, its molecule changes shape and binds to the auxiliary protein CIB1, delivering an enzyme to the target gene using the TALE system. This procedure takes no more than 30 minutes.
New high-precision techniques allow you to add and remove epigenetic labels on specific target genes. But all these tools are not yet used in humans – they are still undergoing laboratory tests.
"VD" Will it be possible in the future, by removing negative genetic "marks", to stop aging and increase life expectancy?
A.D. I am sure that the secret of centenarians lies precisely in the epigenomes of their cells. Molecular biological switches affect the so-called life extension program, which practically all organisms have, from yeast to humans. These programs, if they are included, allow some of us to maintain health and vigor until old age. Now this topic is being actively studied. As for the prolongation of life, there is an illustrative example: a working bee lives for six weeks, while a queen bee lives for six years. With full genetic identity, they differ only in that the future queen bee is fed royal jelly for several days more during development than an ordinary worker bee. As a result, they form different epigenotypes and get such a huge difference in life expectancy. The epigenetic nature of diseases (for example, cancer, diabetes, etc.) is also being investigated and new methods of their prevention and treatment are being sought. If it is possible to study the molecular epigenetic mechanisms of age-related diseases, it will be possible to successfully counteract their development.
"VD" What prospects does epigenetics open for humanity?
A.D. The time of the dominance of genetics is over. We are on the threshold of the formation of a new biological thinking, in the process of transition to a post-genomic society. All cell genomes are the same, having studied one of them, you can understand everything. But each person has thousands of different epigenomes. When all their diversity is studied, unprecedented prospects will open up for new research and treatment methods for a variety of diseases, ranging from mental disorders to HIV and oncology. In the end, epigenetics will be able to accomplish what genetics failed to do – complete the biomedical revolution of the XXI century. Preventive medicine, oncology, pedagogy, psychology, psychiatry, gerontology, evolutionary biology – all these branches are strongly influenced by the laws of epigenetics, and their development directly depends on discoveries in this area.
DossierAriane Giacobino
Leading geneticist at the University of Geneva
Head of the research group at the Swiss Center for Applied Human Toxicology (SCAHT)
Graduated from the University of Geneva
Associate Professor at the University of Pittsburgh Medical Center (Pennsylvania, USA), Faculty of Molecular Genetics, from 2003 to 2006
Conducts medical consultations for patients with genetic disorders, and in parallel – studies in the field of epigenetics, designed to determine the influence of the environment on gene expression and human diseases.
Member of the American, European and Swiss Society for Human Genetics.
Portal "Eternal youth" http://vechnayamolodost.ru06.04.2015