—Could you name a discovery that has significantly transformed biology as a science in the past 20–30 years? Something akin to the paradigm shift that Kuhn wrote about.
— Biology studies life in all its forms. Life is incredibly diverse. There are things that are essentially the same across all life forms. I'm primarily talking about the genetic code, the central dogma of molecular biology, certain metabolic pathways, and catalysis. However, this knowledge doesn't form a universal paradigm. There will always be exceptions, and textbook knowledge can't be directly applied to rationally and purposefully modify any given organism or cell to imbue them with desired characteristics.
The theory of evolution remains central to everything. There is nothing more crucial for understanding life. It's not paradigms that are changing, but our capabilities. New, increasingly powerful methods are emerging, yielding more and more data. The sheer volume of data often makes it impossible to systematize. But perhaps there is no real need to systematize it. Life has no other principle than to simply exist, and merely describing it in all its diversity at the molecular, genetic, cellular, and organism levels leads to significant discoveries, some of which have practical applications.

— Yet today, mathematicians are widely using bioinformatics to extract new knowledge from the vast array of biodata.
— I believe that bioinformaticians greatly overestimate their own importance. It is merely one of many methods for gathering information about biological objects. I was educated in the tradition of Professor Spirin, who claimed that theoretical biology is pursued by those who are inept in practical work. Mathematicians lack biological thinking, so without a biologist to guide them, they are like a headless tool. It's not a coincidence that the world's best bioinformatician Eugene Koonin is not a mathematician at all. He graduated from the Department of Virology at Moscow State University.

— We often hear about mathematical thinking. But what constitutes biological thinking? What makes it unique?
— You need to know a great deal about everything from various sources and be capable of identifying connections and analogies where they aren't immediately obvious. This is fostered by a classical biological education that encompasses all branches of knowledge, from invertebrate zoology to molecular biology and biochemistry. It produces a comprehensive worldview that allows one to formulate non-trivial hypotheses, largely based on intuition. Upon learning some new fact, usually outside your field of expertise, you can use it to fill in missing links and approach a problem that personally interests you from a new perspective. The ability to adeptly handle new facts  and ideas, build new concepts from them, and then experimentally test them using any available methods is paramount in contemporary biology. However, you must understand that you will never achieve complete understanding. Biology is an endless, lifelong pursuit.

— You study two colossal communities, bacteria and viruses. During the pandemic, the latter garnered the attention of the entire world. What new insights have we gained about them through the lens of evolutionary theory? What's your stance on the concept that all life essentially originated from viruses?
— Indeed, some individuals, including Koonin, are promoting a somewhat crazy theory of how cells could have evolved from viruses. That seems implausible, given that today's viruses cannot survive without cells — they are intracellular parasites. On the other hand, cells are significantly more complex than the most intricate viruses, and life should have evolved from simple to complex.

— Does that mean viruses appeared before the cells they later began to parasitize?
— There must have been some form of pre-cellular proto-life, as a cell is an extremely complex structure that couldn't have spontaneously emerged from nothing. It possesses a membrane, energy consumption mechanisms, division, a system for genetic information transfer that ensures offspring cells resemble the parent cell, and so on. The question of how such a sophisticated functioning system came into existence is a fundamental one in all of biology. Because if you can create a functioning cell, the subsequent emergence of diverse life forms is merely a matter of time and chance. Everything will naturally occur through Darwinian selection and the imperfect transmission of genetic information from one generation to the next. They say that if you give a monkey a million years and a typewriter, it will eventually write War and Peace. With the evolution of life, things are much more efficient: if writing War and Peace enables the monkey and its offsprings to reproduce more rapidly, a positive feedback loop will be created, and the book will be written not by random trial and error, but through iterations that create the illusion of purposeful progression towards a goal.

— Was RNA the carrier of proto-life?
— It seems that way. RNA molecules currently hold a somewhat secondary position to DNA and proteins, but perhaps RNA "conceived" DNA to store information and proteins to effectively perform useful tasks, such as catalyzing chemical reactions. Just last week, a fascinating article was published that experimentally demonstrates that ancient RNA might have been capable of all this due to the presence of special chemical modifications that are very rarely found in modern cellular RNA.
As for viruses, the conventional viewpoint is that viruses relate to a cell in the same way a computer virus relates to a computer. This is a great analogy, as a virus is essentially a genetic program that allows the cell's resources to be reconfigured to reproduce new viruses and spam them, infecting other cells. An alternative point of view suggests that some ancient viruses teamed up to create a cell. This immediately raises the question: how did those viruses reproduce without cells? Perhaps they parasitized each other (we see similar examples in modern life), or maybe the conditions on early Earth allowed viruses to reproduce without cells. When I was at university, people told stories about a fight between two evolutionists from the evolutionary biology department. One of them allegedly grabbed the other by the throat and yelled, "Were you there during the late Silurian period?" I wasn't there, so I can't say. Ultimately, we will need experiments. Conducting them is challenging. We have a poor understanding of the conditions that existed billions of years ago.

— Does human society more closely resemble a viral or bacterial community? There are contemporary studies on the social organization of the virus universe that say viruses are capable of self-sacrifice.
— Both viruses and bacteria possess the ability to self-sacrifice. However, they lack self-awareness, so such concepts are not applicable to the way viruses behave. Generally speaking, communities of same-type bacteria and viruses somewhat resemble a caricatured version of North Korea or a dystopian novel.

— Could you explain why?
— You see, multicellular organisms have genetic differences. So, from an evolutionary perspective, it's beneficial to love your own children, not those of others. This is simply because after we die, our genes continue to live on through our offspring. Therefore, it's logical for us to strive for the success of our own progeny and, if possible, hinder others, as resources are limited (I'm obviously exaggerating here). Clearly, at least in humans, there are additional factors such as morality, religion, and coercion that animals lack and that influence how we live and interact with each other. In a grotesquely perfect dictatorship, on the other hand, individuality is irrelevant. Everyone is identical, and the primary focus is on the survival of the nation. This is pretty much how things work in bacterial and viral populations. Bacteria within a single population are almost genetically identical — they are clones of each other. So, as a bacterium, I could sacrifice myself for your offspring, and you could do the same for mine. In other words, each bacterium is like the Alexander Matrosov[1] of the microbial world. From an evolutionary standpoint, it's better for it to die along with the virus that infected it than to allow the virus's offspring to develop. Because the viral offspring will go on to infect many more cells. Overall, one could anthropocentrically view this as "altruism", but it's simply an evolutionarily advantageous strategy. Populations where individual bacteria can act like Alexander Matrosov are more adaptable than those where cells don't act that way.

— Could you please talk about your work on the Atlas of Microbial Communities? What is it going to look like and what is its purpose?
— The Atlas is an interactive map that will display microbial communities residing in various geographical points across Russia and show how the composition of those communities changes over time. Similar projects exist globally, but nothing of this sort has been done in our country yet — Russian scientists have only been involved in international consortia. Our primary focus will be on studying communities living in the seas of the Northern Sea Route. This will presumably involve participating in expeditions on research vessels and collecting and analyzing tens of thousands of samples over several years.

— How well do we understand the microbial communities living in those places?
— Marine microbial communities are generally understudied, especially in the Arctic. One of our objectives is to discover microbes capable of producing bioactive substances, such as antibiotics. Most of the antibiotics we currently use are produced by microbes that scientists isolated from the environment during the 1950-60s, a period now referred to as the "golden era of antibiotics". At that time, they primarily studied soil samples, and there was even a trend where large American and European pharmaceutical companies asked their vacationing employees to collect samples from around the world for microbial research. But the "golden era" ended because the number of cultivable microbes in soil samples turned out to be quite limited. Scientists kept discovering microbes that produced the same, already known antibiotics. This eventually led to the current crisis and the emergence of bacteria resistant to most of the antibiotics in medical use today.

— So, do marine microbes appear more promising these days?
— They are significantly less studied, hence there is potential to discover something new and intriguing. This type of research is being actively pursued globally, but primarily in warmer seas. Such research has not been conducted in the Russian Arctic yet, due to the lack of appropriate technology. Our work has mainly followed the traditional approach where an expedition goes to a specific area, biologists collect samples, then isolate microbes from them, and cultivate them in the lab. However, it's now evident that only a tiny fraction (less than 1%) of microbes present in natural samples grow on the nutrient media we provide for them in the lab. Meaning, over 99% of microbial diversity remains a mystery, an unexplored territory in the microbial world around us. Modern genomic analysis methods are providing access to this hidden microbial diversity. We no longer need to cultivate them in the lab. Instead, we "read" their DNA and identify genes that could be of interest, such as genes responsible for the biosynthesis of new antibiotics.

— How will the work at sea be organized?
— Each watercraft operates with a large team of researchers, which includes geophysicists, oceanographers, and scientists from other fields, in addition to biologists. Our team will set up onboard microbiology labs. Ideally, we expect that they will not only collect samples and extract DNA but also perform sequencing (read DNA sequences) on portable devices right on the ship and then transmit the data to the mainland in real time, say, from the Kara Sea. Much like radio operator Krenkel, who transmitted information about Soviet polar explorer Papanin's party meetings from an ice floe. In other words, the collected data can be analyzed in real time.

— How will you choose locations for sample collection? And are there any particularities in the sampling process?
— We are obviously limited by the ship's route. One way is to collect water from different depths, filter it to remove inorganic particles or plankton, and then extract the DNA of the microorganisms living in it using standard methods. The second option is to work with bottom silt sediments, which contain a vast number of microbes and always offer something interesting to find. Thirdly, there are special locations, like methane yields on the ocean floor, which create unique ecological niches and consequently, unique microbial communities. The fourth approach involves studying the microbes residing within marine invertebrates such as sponges, worms, crayfish, and other species.

— Most of your work revolves around molecular scissors — CRISPR systems, which are used to "cut out" genome segments and insert new ones in their place. We now know that this is a strategy employed by bacteria to combat viruses and that it is part of their adaptive immunity. Do we know when and at which stage of evolution it emerged? Can it be traced in any way?
— Tracing it is quite challenging. This is the concept of LUCA, the first cell from which all present-day cells have evolved. All LUCA descendants can be split into three major groups. The first one is bacteria, cells without nuclei. The second one is nucleated cells, which eventually gave rise to multicellular organisms, all plants and animals including humans. And the third one is archaea, also non-nucleated cells, which significantly differ from bacteria and share several characteristics with nucleated cells. Interestingly, both bacteria and archaea possess CRISPR systems, but we do not. This implies that either our cells lost this ability at some point during evolution, or CRISPR systems developed after the separation of nucleated cells from non-nucleated ones.
Another difficulty is that CRISPR systems are capable of horizontal transfer, meaning their genes can hop around within the genome and between different organisms. Therefore, it's impossible to pinpoint when they first appeared, as evolutionary time is gauged by the accumulation of mutations over the course of gradual evolution. However, if someone breaks the rules by jumping around randomly, it makes age determination complicated. For instance, there are certain CRISPR systems that are strikingly similar to each other and are found in the genomes of widely separated archaea and bacteria. Conversely, closely related bacteria can possess very different CRISPR systems. It's a complex matter.

— To what extent do we know which parts of the genome can spontaneously rearrange themselves and how?
— There are numerous mobile genetic entities, viruses being one of them. The human genome contains approximately 25,000 genes, which only constitute a small fraction, a minuscule percentage of our entire genome. Our knowledge about the remaining, larger portion is quite limited. A significant part of that potential genetic "junk" consists of viral remnants that at some point integrated into our ancestors' genome, became defective, but for some reason still persist in our genome. There are hundreds of thousands of such former viruses in the human genome. Occasionally, they jump around sluggishly, altering their position within the genome in individual cells of our body. If they jump incorrectly and mess up a useful gene, it could lead to problems. For instance, we know that some forms of cancer develop that way.
I recall that the first book I read about horizontal gene transfer was titled Genome Inconstancy. It was written in 1984 by Roman Khesin from the Institute of Molecular Genetics of the USSR Academy of Sciences. Despite its dryness, the book revolutionized the beliefs of many biologists at the time. We suddenly realized that on the evolutionary tree, genes can leap from one branch to another, thereby endowing organisms with new traits that didn't evolve gradually but appeared abruptly due to transfer. However, the extent of such transfer only became clear after we learned to decode genomes and found numerous instances where genes were present where they shouldn't be. By the way, antibiotic resistance in bacteria spreads precisely through horizontal gene transfer.

— The 2020 Nobel Prize in Chemistry was awarded for the discovery of the CRISPR systems. Since then, this biotechnology has become so prevalent that you can now purchase a kit online that enables you to edit your genome right in your own kitchen.
— Well, that's just hype. It doesn't make any sense. You need both proper education and equipment to use CRISPR.

— But the volume of serious research is also incredibly large. How close are we to developing drugs that use CRISPR systems?
— There aren't any working medications yet, but there are several that are undergoing clinical trials. There are fields where CRISPR will almost certainly be effective in the future, such as treating certain types of blood cancer. If the genetic cause of the disease is known, we can extract cells with the genetic defect from the patient's bone marrow. We can then cure the defect, restoring the DNA sequence to normal using CRISPR molecular scissors. And finally, we can multiply the edited cells and reintroduce them to the patient after first destroying their damaged blood-forming cells. The main breakthrough here is that the issue of immunological compatibility is completely resolved, as the patient is implanted with their own cells.
In Japan, where there is a high percentage of elderly people, scientists are conducting experiments to halt age-related retinal degeneration and prevent vision loss. Many countries are studying the use of genetic editing to fight muscular dystrophies.

— What does it look like in practice? How does the drug get to where it's needed?
— The range of diseases that could potentially be treated with gene editing in the future is likely limited precisely by the ease of delivering the editor to the damaged cells. For instance, in the case of Duchenne muscular dystrophy, you can inject a protein — a genetic editor — into the muscle and hope that a certain number of cells will be edited and become normal. From there, the disease will, in a way, start working for you. The damaged cells will gradually die off, and healthy, edited cells will proliferate and replace the lost damaged cells. But as soon as we start treating, for example, solid tumors of the liver, kidneys, brain, etc., it becomes clear that a genetic editor is powerless. The fundamental problem of all modern medicine is targeted drug delivery. Until we can deliver the necessary CRISPR system to where it's needed, and not just to one but to most of the damaged cells in an organ, its use in medicine remains limited.

— Okay, so how extensively is this already being used on living organisms — pigs, horses, etc.? Even embryonic modifications using CRISPR systems are not banned to perform in animals.
— Yes, since a pig doesn't have an immortal soul, you can do whatever you want. The only question is why. Real-world application requires solving a specific commercial problem. For instance, a few years ago genetically edited mushrooms started appearing in U.S. stores. Regular mushrooms darken when cut, quickly losing their presentable look and ending up being thrown away in large quantities. This issue was resolved using genetic scissors — they removed the gene that produces the coloring substance. Now unsuspecting housewives are buying old mushrooms, and everyone is happy.

— Was it worth the effort?
— I suspect that the mushroom market is worth billions. They're cultivated on manure, which is produced by cows that also generate methane, and so on. By prolonging the shelf life of mushrooms in supermarkets, substantial benefits can be reaped throughout the entire chain. If the market embraces it, that's fantastic.

— Other intriguing research involves using CRISPR technology to create new animal breeds and plant varieties. Should we anticipate super horses and super apples?
— Yes, there is so much work being done in that area today that the term "CRISPRing" has emerged. Everyone is CRISPRing everything... But in reality, there is not much progress when it comes to livestock. The truth is, super horses and super apples have already been developed. All animals possess growth factors, proteins encoded by specific genes. They work while we grow and then stop working, halting growth. Naturally, any entrepreneurial individual would be tempted to prolong the activity of that gene to get perpetually growing pigs. But it appears that it doesn't work, simply because pig breeders of the past worked hard for centuries to select pigs that were most profitable for breeding, that is, those that grew quickly. It seems that the existing breeds have exhausted their biological potential. The "Pig Project" has reached its limit, and additional growth hormone production has been futile.

— The biggest buzz was about genetically altered Chinese babies. By the way, He Jiankui has already been released from prison.
— Naturally. He spent long enough there as it is.

— How easy is it to perform such a manipulation today? What does it take? And how much does it cost?
— If you know what you're doing, it's not complicated. You need an IVF clinic, access to fertilized human eggs, a functional method to introduce a genetic editor into those eggs, the gene you wish to edit, and mothers willing to carry the edited embryos. Roughly speaking, you add a genetic editor aimed at a specific gene to a test tube with a fertilized egg, and the process begins. When the egg starts dividing, you can take some of the embryo cells and check if there has indeed been a change in the DNA. Then, If you're so inclined, you can implant that embryo into the mother. If you don't tell her anything, she won't know about the editing and will carry the baby to term.
So technically, there is nothing difficult about it. However, there is an insurmountable issue in that we don't know exactly what needs to be altered. You need to have some sort of idea or goal. As of now, no scientist knows what needs to be changed to, say, alter the shape of a child's nose or make them smarter, more attractive, or healthier. Undoubtedly, there are many inherited genetic diseases, but they can be prevented without any editing through genetic analysis, counseling for prospective parents, and IVF.

— You were appointed as the director of the country's largest genetic center a year and a half ago. What's its current status?
— We're talking about a major genome sequencing center being established by Rosneft[1] in collaboration with the state, under the genetic technologies development program. We plan to identify up to a hundred thousand Russian genomes and establish a modern human genetic data repository. The analysis of this database will allow us to more efficiently identify genetic diseases and come up with ways to treat them. The center's facilities are all set up, and we're currently busy procuring equipment.

— There are several ongoing projects worldwide aimed at establishing large national genetic databases. What sets them apart?
— There are dozens of such initiatives globally. The first one was in Iceland, followed by projects in the UK, Denmark, Estonia, China, and so on. There are also several large international projects. In the UK, they initially had a project for 100,000 genomes, which started in 2013 and was successfully completed in five years, and now they're working on a project for five million genomes. These projects are spearheaded by the Genomics England consortium, with support from the Department of Health and participation from private companies that manufacture DNA sequencers, devices for reading DNA sequences.

— The British selected genomes based on specific diagnoses. Are there other criteria for genome selection?
—They were interested in genetic diseases and cancer. There are also projects with an ethnic focus. For instance, the genomic initiative in Estonia did not include research on the Russian-speaking population. It was more like an attempt to discover the elusive Estonian "soul". The thing is, for many native Estonians, there is different information available, such as records in church books that have been preserved for centuries. This allows for fascinating retrospective studies to understand how certain traits have been inherited across generations. Iceland has an even better situation in this regard. In Russia, unless we're talking about indigenous peoples, this is unfeasible due to the extensive mix of ethnicities, making it impossible to verify anything for certain.

— How important are genetic differences among ethnic groups for contemporary medicine?
— Historically isolated groups of people do indeed exhibit genetic differences, in the sense that certain DNA sequences are more prevalent within a group than outside it. The existence of ethnic-specific genetic markers can influence the likelihood of certain diseases or the effectiveness of specific drugs on an individual. One of our center's objectives is to obtain reference genomes, or the genetic "portrait", of our country's peoples.

— How does this work in real practice? Where will all this data be stored? How much does an informationally sequenced genome weigh? About six kilobytes?
— Each person's genome is a six billion letter text split into 46 chromosome volumes. The data storage we're building will be among the largest in Russia. The center is physically situated at the Institute of Bioorganic Chemistry and is called the Biotech Campus.

— How is information security structured around such projects globally? Do individuals who provide biomaterial have the right to access information about their genome?
— The project's participants are volunteers. They provide informed consent for personal data processing and for their blood-derived DNA to be sequenced, analyzed for research purposes, and stored in a database. Meanwhile, the data is anonymized. Therefore, if a scientist plans to analyze a set of genomes from the database, they won't know which specific individuals they are associated with.

— Can an individual access their own analysis? Suppose they want to find out if they're a born hockey player.
— In general, anyone can pay to have a full genomic analysis of their DNA and receive some information about themselves. This includes data about ancestry and potential medical predispositions, often resembling a genetic horoscope. In Russia, several companies like Atlas Biomed and Genotek offer such services. We will provide this information to our volunteers for free. However, the results of these analyses shouldn't be interpreted as a diagnosis or a call to medical intervention. And certainly not as a reason to become a hockey player or not.

— Aside from the medical aspect, the perennial question is how the genome encodes personality traits, perhaps even genes of genius.
— The question is incorrect because it's phrased wrongly. Our personality is a combination of genetic predispositions, upbringing, time frames, society, the place we live in, chance (like a brick suddenly falling on your head), and, very importantly, luck. If you're trying to find traits in the genome that define essentially indefinable concepts like beauty, talent, and genius, you're destined to fail or, more accurately, to mislead the public. The same applies to the concept of a national genome. For instance, there is no such thing as a "Russian genome". People become Russians not because they possess a specific gene but because they were raised in this country. So attempts to work with the genome as a whole to find something beyond medical aspects are bound to fail.

— Not long ago, during the pandemic, we observed a remarkable phenomenon where belief in science and medicine coexisted with total distrust in science, manifested in the anti-vaccination movement. How can these coexist?
— I believe there is a contradiction in the phrase "belief in science". Although, perhaps "belief" isn't entirely incorrect here since we're talking about people who aren't professional scientists but have a scientific, rational worldview. And some people don't have that. Science is often seen as a governmental matter, so those who distrust the government tend to also distrust science.
I had the opportunity to talk to a woman who was researching a unique roadside ritual culture in the U.S., where wreaths are hung at accident sites along the road. I was under the impression that such a thing didn't exist in the States, as I had never seen it before. However, it turns out that it doesn't exist in the States I'm familiar with, but it's quite prevalent in the less prosperous Spanish-speaking parts of America. The researcher hypothesized that citizens who don't feel integrated into society at large tend to create their own rituals and subcultures. In other words, a subculture arises when its members don't feel they are part of the overall national process. This is referred to as being disenfranchised. I believe that health activists, anti-vaxxers, those who believe in a unique Russian way, in Cthulhu, homeopathy, and the like are also essentially just unhappy and disadvantaged people.

— So, it's essentially two different countries.
— Yes. But it's not just two. There are many different non-intersecting countries.

— In Russia, trust in scientists has nearly halved over the past five years according to sociological research.
— I'm not familiar with such data. It could be an unexpected result of efforts to elevate the status of scientists by officially stipulating that they should earn significantly more than the regional average salary. If this leads to the perception that there is a lot of money but no improvement in science, how can there be trust?

— Do you believe in progress and the idea that the world is changing for the better?
— Yes, absolutely. I definitely wouldn't want to live in the Middle Ages, Tsarist Russia, or the Soviet Union. But I believe more in personal progress.

— How do you raise your children? Do you follow any specific rules? Do they have any inclination towards natural sciences?
— The older I become, the less faith I have in parenting rules. I have three children, each remarkable in their own way. My eldest son is a political scientist and social philosopher by education. But in reality, he is an unemployed anarchist. He greatly admires Machiavelli's The Prince and uses it as a source of inspiration when interacting with others. And he wonders why no one likes him. My other son graduated from one of the top physics and math schools in the Midwest. He is about to graduate from university and will be working in IT. My youngest daughter was born in Russia and still lives with me. Her favorite book is Lord of the Flies, and she has a rather noir perspective of the world. She is 17 years old, has been accepted into university, and will be studying art design. In other words, none of them are involved in science, and thankfully so.

— Many believe that the current generation is better and more honest than us.
— I wouldn't call them superior, but they are significantly more open. It's simply a different species.