‘The Set of Genes in the Person’s Body is Permanent’ – Pathophysiologist Vasyl Nagibin

 ‘The Set of Genes in the Person’s Body is Permanent’ – Pathophysiologist Vasyl Nagibin

Which two factor groups influence the origin and progress of diseases? Why the same environmental conditions have a different effect on human health? What are the non-coding RNAs and how could they be used in biohacking? These and other questions have been answered by pathophysiologist Vasyl Nagibin in the interview with Biohacking Conference Kyiv 2020.

Vasyl is a Candidate of Medical Sciences and a senior research associate at the Department of General and Molecular Pathophysiology at Bohomolets Institute of Physiology at the National Academy of Sciences of Ukraine.

Read more details about the role of genes in disease progressing processes, problems of gene therapy and the peculiarities of non-coding RNAs in the interview below.

The interviewer: Biohacking Conference Kyiv (BCK)

The respondent: Vasyl Nagibin (V.N.)


BCK: What factors influence the origin and progress of diseases? Can they be completely eliminated? Why?

V.N.: Two general factors affect this process: environmental factors and human traits (genetic or acquired) forming its proneness to certain diseases. Thus, all diseases can be divided by two formal groups: the ones with prevailing environmental factors (injuries, infections) and the ones with prevailing human traits (congenital pathologies). In between of these two groups are the diseases without the visible cause. Nevertheless, they are the most widespread and consume the major part of human resources: diabetes, hypertension, atherosclerosis, alcohol addiction, mental disorders, tumors, autoimmune diseases.

The experience and logic show that complete elimination of carbohydrates and wine out of the diet can barely overcome diabetes and alcohol addiction. Also, same as with fighting infections, vaccinations have proven to be really efficient, unlike simple destruction of bacteria and their carrying agents.

For some people it’s obvious that many potentially dangerous environmental factors can be avoided. But others are definitely sure that the person was just born this way. It’s important that certain traits of the person are not always inborn. They are formed under the influence of the environment the same way as the ambiance, e.g. social circle is formed by the person depending on his/her genetically defined needs.

Thus, any disease is a tightly interlaced dynamic combination of many factors of both groups. Fighting diseases by eliminating just one factor is a false way.


BCK: What factors are key for the human health?

V.N.: Human health and the possibility to preserve this health is based on the range and degree of developing reactions to environmental factors. The set of these reactions is similar for everyone: from biological reactions (typical pathological processes) to purely humane (changes in higher nervous functions).

Inanimate nature has no reactions and, as a result, can’t get sick. All reactions are possible because of complex interactions of various chemical substances, first of all, protein with their information stored in our genes.


BCK: How genes influence human health and its capabilities?

V.N.: The set of genes in the body of a certain person is similar and unchangeable. But the set of genes related to the same protein (attribute, quality, reaction) is diverse and its combination makes us different, although it features all human attributes. This diversity makes standard and typical human reactions to environmental factors different for every person, ranging in the development rate, range and other peculiarities. Thus, based on such combinations, each individual has qualities that provide benefits in certain environmental conditions but cause to diseases in other conditions. So, things that are not dangerous for you, may be a poison to me.

If we don’t consider pure genetic diseases (congenital anomalies), than health is a set of reactions to external factors, adequate to the given environment by force, speed and flexibility and having a necessary safety margin for adapting to the wide range of environmental changes. If any reaction is weak or too strong in such conditions, it may lead to development of disease. In other conditions, it doesn’t show up painfully, so we can talk about genetic predisposition.

In the case of such predisposition, as in the case of any genetically determined trait, we can talk not only about its presence, but also about its development (training). In the process of life, reactions develop or, on the contrary, degrade under the influence of the same factors of the external environment, lifestyle, ambience etc. The lifestyle and ambience, as well as the external environment factors can be changed by a person in the search for comfortable living conditions that meet his needs. And this is a loop. Thus, this process is dynamic and, as a rule, leads to a decrease of functional load on some systems and almost maximum load on others.

Genes form all the reactions necessary for existence, their functional range, the ability to change (flexibility) and the different degree of some reaction activity in comparison with others. It is impossible to go beyond the gene limits, and modern science is only on its way to developing methods for changing human genes for medical purposes.


BCK: How promising is gene therapy? What diseases can be treated with it?

V.N.: From what we’ve discussed, the prospects for gene therapy are enormous. By changing genes, we can create the widest possible range of human reactions to environmental factors, which will ensure adaptation to a variety of conditions, and will not lead to the development of diseases, ideally in any environment acceptable for life.

With the help of gene therapy, it will be possible to prevent those diseases that are most common in modern civilized countries – diseases with a hereditary predisposition. Of course, this will not protect from being attacked by a tiger for example, but such cause of illness is an accidental and excessively strong environmental factor. Fortunately, it is less and less common, especially if you adhere to traffic rules and other safety measures.

The difficulty of predicting external conditions is considered to be some limitation on the path of widespread use of gene therapy. This is because the benefits of being in one environment can be potential threats to living in another. This is especially noticeable on the example of the most flexible systems in our body – central nervous and immune systems.


BCK: What problems can happen because of gene therapy?

V.N.: One of the main problems of gene therapy is the impossibility to apply the technology for adult people. In this case, it is necessary to change the sequence of nucleotides in all cells, or at least in all stem cells, and this is impossible.

Therefore, an important goal for modern science is the development of such methods of influencing the human genetic program that will be effective for adult individuals. This eliminates the need to guess possible environmental factors that a person might encounter throughout the life. Theoretically, we could change a certain genetically determined function in some cells without affecting others, and then, when the environmental factors change, return everything to a previous state.


BCK: What role may non-coding RNAs play in disease development?

V.N.: The non-coding RNAs and other epigenetic mechanisms can be used exactly for such purposes.

Non-coding RNAs are RNA molecules that do not carry information about the primary structure of proteins, but perform auxiliary and regulatory functions. For a long time, the knowledge about their main role has been limited only to the concept of transport of amino acids to ribosomes during the synthesis of new proteins. Later, their significance was discovered in the intracellular response to viruses. And from that moment, it became obvious how they can be a powerful tool of precise regulation of their expression without gene changing. Some of them indirectly regulate the number of protein molecules formed from a given gene at a given moment, others affect the very ability of a gene to be expressed, and others regulate the amount of other noncoding RNAs or ‘activate’ the whole chromosome at once.


BCK: How can non-coding RNAs be used to diagnose, predict and treat diseases?

V.N.: Any change in the vital activity of a cell entails a change in the gene expression profile. Some will begin to actively express, others will stop. Some will express many protein molecules, while others will not. Some will be active for a long period, others – only for a very short time. These changes will inevitably affect the qualitative and quantitative composition of intracellular RNAs, including regulatory non-coding RNA molecules, which can subsequently enter the extracellular space and biological fluids by various mechanisms. There they can be found and evaluated.

At the moment, noncoding RNAs of blood, urine, excrement are already used for early and highly sensitive diagnosis of oncological diseases, in the development of methods for assessing the effectiveness of therapy and prognosis of the disease.

In addition to sensitivity, methods based on the determination of noncoding RNAs, in particular microRNAs, have such advantages as non-invasiveness, relative cheapness, the possibility of dynamic observation and the speed of observed changes over time, the individualization of the forecast, and almost inexhaustible range of parameters that can be controlled with their help.

Today, the main disadvantage of this method is the lack of study and lack of systematization of all noncoding RNAs: their number is truly impressive, and the main discoveries and work on systematization are still ahead.


BCK: Is it possible to increase longevity with the help of diets, sports, dietary supplements, microflora correction and other biohacking approaches?

V.N.: Certainly. Lifespan has never been so large as now, despite all wars and pandemics. And this is not only the result of hygiene, the invention of antibiotics and the evolution of medical devices. It is also a consequence of an increased awareness of people in such matters as personal health, conscious lifestyle changes, dietary adjustments and simply taking care of oneself.

Noncoding RNAs represent a new and very promising object for biohacking. The search for the most simple and affordable methods of influencing noncoding RNAs can become, without exaggeration, a new milestone in biohacking, along with understanding the importance of diet or understanding the possibility of correcting habits.


BCK: Is it possible to achieve immortality from a biological point of view and why?

V.N.: No, because an organism, like any matter, cannot exist forever. This will become possible if we learn how to transfer consciousness and experience from one biological body to another, but this is not exactly a biological immortality.

 

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