—Your last name is self-explanatory. Chumakov is a synonym for "virologist"!
— Close, but not really! My father, Academician of the Soviet Academy of Medical Sciences Mikhail Petrovich Chumakov, founded the Institute of Poliomyelitis and Viral Encephalitides, and pioneered polio vaccination. He contributed to the discovery and study of the tick-borne encephalitis virus, Crimean and Omsk hemorrhagic fevers, and many other, no less terrifying infections. My mother, Marina Konstantinovna Voroshilova, who also was a polio researcher, developed the concept of beneficial human viruses, and proposed a method that harnesses non-pathogenic viruses for non-specific protection and treatment of both viral and non-viral diseases, including cancer. All my brothers are biologists. Ilya is a molecular biologist who worked on human genome decoding in France. Petr, a corresponding member of the Russian Academy of Sciences, works at the Engelhardt Institute of Molecular Biology. The youngest, Alexei, spent most of his career studying molecular biology of cancer at the University of California in Los Angeles, and now teaches at Sechenov Medical Academy in Moscow.

— Your father was a stalwart Soviet patriot until his last breath. What was his reaction when you left the country in 1989?
— My father was a genuine patriot and a staunch communist of 1920s mintage. Unlike 1980s communists, there was no trace of cynical opportunism in him. To my regret, I never saw him again after I left in 1989. He died in 1993. But there was never a hint of reproach in our letters to each other. He saw what was happening all around him. It made him feel proud that things were really going my way where I was. But it surely would have pleased him if I had returned, sooner or later.

— Both your parents had contracted severe infections during their work that could have been lethal. But that didn't stop them, did it?
— Risk was always part of their profession, they knew what the deal was. As a young man, my father joined some pioneering expeditions to the Far East, and he participated in the discovery of the tick-borne encephalitis. My father was always a very driven person. The story of how he got infected tells a lot about him. He was so impatient that he had to perform the autopsy of the body of a person killed by tick-borne encephalitis, so he might examine the brain tissue. Not having the proper tools at hand, he cut his hand with some skull bone splinter and fell ill. He ended up losing his hearing and mobility in his right arm. But this did not hinder his work at all: my father continued his research and discovered dangerous viruses for the rest of his life.

— What about your mom?
— My mother caught polio in Sukhumi. There was a monkey colony there where scientists performed experiments to study another plague of the 20th century: poliomyelitis. I'm not really sure how my mom got infected. Most likely she was bitten by a monkey. Then my mother fell ill, and I caught polio from her. I had just learned to stand up straight on my own and was taking my first steps. I had a really high fever and forgot how to walk, but eventually I recovered. My mom, however, had to use a cane for a few years.

— Were you ever afraid of getting infected?
— I have never dealt with dangerous viruses in my life. My current research interest is the development of new vaccines. I'm part of the Bill & Melinda Gates Foundation's novel polio vaccine project. We are working on a new, safer and genetically more stable, polio vaccine based on an optimized genome design. The vaccine is already in use and has demonstrated excellent results. I also do deep sequencing-based molecular monitoring of vaccines. It was my focus when I first moved to the U.S. The method we are working on at this time will enable us to analyze such an important virus property as genetic stability. Genetic stability is key to the safety and effectiveness of live vaccines. If the method gets approved, not only will it have many practical benefits, it will get a major ethical issue out of the way: vaccine manufacturers will no longer have to test vaccine batches on animals. As the matter stands now, some 200 monkeys or transgenic mice have to be sacrificed to assure the safety of each batch of the vaccine.

— How do live vaccines work as opposed to inactivated vaccines?
— Live vaccines create a specific immune response in the form of antibodies or cellular reactions, but they also stimulate innate immunity – the body's inherent defenses against any infection. These are entirely non-specific mechanisms discovered almost a hundred years ago. However, their molecular mechanisms are not fully understood yet. The conventional explanation is on the surface: viruses trigger the production of interferon. This protein is part of the natural immunity. It makes the body less susceptible to pathogens.

— How long does it last?
— The effect is supposed to last a couple of weeks at most. But recently, a phenomenon was discovered termed “trained innate immunity”. It turns out that when an organism is subjected to an infectious injury, a pathogen, or a live vaccine, the so-called epigenetic modifications will occur in the organism. The genes responsible for producing the components of innate immunity become activated. In this state, the gene is like a runner ready to go, ready to spring into action at any moment. This is like reading an encyclopedia: you flip through the book looking for information, and when you find the place you wanted, you highlight it with a bookmark for easy reference next time. The same thing happens here: the organism leaves a bookmark so it can promptly activate the same gene when needed. This is very likely a universal biological phenomenon: it is in the body's best interest to keep the recently used genes on high alert. What all this adds up to, is that the administration of a live polio vaccine may give you long-term protection against all infections.

— In the United States, you work at the FDA Office of Vaccine Research and Review, which issues permits to use new medicinal products. You oversee 35 labs, each working on its own virus or bacterium. Why keep working on “old”, well researched infections that are already kept at bay by reliable vaccines?
— First of all, our organizational ideology behooves us to maintain world-class expertise in all areas to be able to make regulatory decisions. Biotech companies come to us to ask for a license or market authorization for their new drugs and biological products. Our effectiveness can be best illustrated by the unprecedented speed of the authorization process for mRNA vaccines against coronavirus.
And second of all, there's no such thing as “old” infections. With the arrival of new methods, we're seeing a rapid evolution of vaccines. To give you one example, the whooping cough vaccine developed in the 1950s provided solid protection but caused serious side effects. Scientists came up with another vaccine only to discover a few years later that vaccinated children are able to transmit infection. And now we are seeing a resurgence of whooping cough in many countries. A third generation of whooping cough vaccines is now in the works.

— Is it possible for new drugs to cost less than the previous ones?
— No, they usually cost more. After all, they are developed using the latest advances in molecular biology.
When the new hepatitis C drug went on the market, it cost $70,000 per treatment cycle, even though the pills themselves cost no more than $2 apiece. The company had invested billions in development and testing of the drug. Now the company has to recover the investment, otherwise it will never be able to create new drugs.

— In that case, how come only China and Russia resorted to the old, tried, true and inexpensive knowhow of vaccine production during the pandemic? In Russia, the inactivated vaccine was developed by the Chumakov Research Center.
— Only a few manufacturers in the world are equipped to provide the high biosafety level that the production of this product requires. The other reason is that scientists find it boring to repeat old technology. At the time the pandemic hit, there was a lot of promising but untested technologies that no one was prepared to invest in. And now the pandemic opened the opportunity for them to be tested and introduced into practical use.
Another important aspect is related to the structure of the virus. SARS-CoV-2 contains S-protein that is the most important protective antigen. Similar proteins exist in certain other viruses, such as human respiratory syncytial virus. In the 1960s an inactivated vaccine was developed, but it turned out that vaccinated people had a more severe disease than those who weren't. The RSV protein, which is similar to the S-protein in SARS-CoV-2, suddenly started producing "wrong" antibodies that, instead of targeting and killing the virus, assisted it with cell entry. As a consequence, there was a general reluctance to use the same solution for this class of viruses. It's a stroke of luck that this hasn’t happened for inactivated COVID-19 vaccines.

— How often do leaks of dangerous pathogens happen in research labs?
— I believe such events are very rare. But, as the saying goes, once is enough. Authorities will never acknowledge an emergency of this nature, at least not in an authoritarian society like China. Similar leaks are known to have occurred in many different countries, including the Soviet Union. Viruses or bacteria can escape from labs due to negligence. In the 1950s, when biological weapons were developed on a mass scale, a similar emergency took place in the United States. When I moved to America in the 1980s, Fort Detrick housed the U.S. Army Medical Research Institute of Infectious Diseases. They had a building, like a massive water tower, entirely infected with anthrax. It had remained sealed off for a long time, and people walked by it with caution.

— In March 2020, Chinese authorities named Fort Detrick as the probable origin of the COVID-19 pandemic. They did it in response to similar accusations leveled at the Wuhan lab. How easy is it to construct a virus these days?
— Technically, it's really easy with the help of genetic engineering. There are streamlined methods for modifying the genome in viruses or bacteria. Not so long ago, we learned to do this using chemical synthesis alone. You design a new virus on the computer, and then you have a chemical robot to synthesize it.
It's far more difficult to pinpoint the actual spots you need to modify. Many scientists worldwide study virus pathogenicity in order to develop powerful vaccines. As part of this effort, viruses sometimes need to be adjusted and deconstructed to figure out the functional roles of their different parts. This is a standard practice of studying nature. It is likely that someone had acted irresponsibly in China. But whether there was negligence involved or not, we'll never be able to prove anything. The point to keep in mind is that biosafety is always a double-edged sword. Because on the one hand, everything must be done in the best possible measured manner. On the other hand, however, you can't tighten the screws too much and corral all research into BSL-4category. That's where it gets practically impossible to work. If you are to wear a hazmat suit all the time, maybe you can do one or two experiments, but that's it.

— And if we look at Murmansk Oblast as it is now, what would the proportions be?
— Certainly not equal. We may not be using that much intensively: there are cities, mining sites, a few fields… But last century, logging was very active there, and severe fires followed the logging and forest roads. We cut down and triggered fires on much more than a third of the forested areas we used, and these areas are now in recovery. Ideally, we should have as much protected land as we logged, but currently, it’s only 13 percent.

— To what extent is contemporary virology different from the traditional one? It seems like virologists can do a lot more today than their predecessors ever could. Or does BSL-4 get in the way?
— It's a bit of both. Grad student papers these days are top quality: each would have merited a Nobel Prize in the past. But sometimes young scientists are unsure what field of science they're in, as the boundary between virology and general cellular biology becomes increasingly blurred. One day you are studying a virus, the next day, it's a cell, and the day after it's the entire immune system. This approach carries certain risks: researchers may be well versed in the minute details of gene functionality, but ultimately fail to grasp the big picture of how it affects human health. There are very few “old-school”, “classic” virologists left who know all viruses and their effects on the human organism.

— Is the scientific community making any effort to maintain this broad-based level of expertise?
— In a sense, yes. In 2011, a group of globally recognized “classiс” virologists set up The Global Virus Network (GVN) in an attempt to salvage the integrity of the science. The network is led by the legendary Robert Gallo, director of the Institute of Human Virology at the University of Maryland and discoverer of HIV, William Hall of the Centre for Research in Infectious Diseases in Dublin, and Reinhard Kutz, director of The Robert Koch Institute. They invited top scientists from 30 countries to join them in their initiative. From Russia, they invited the esteemed virologist Vadim Agol, who is 93 but still active. Already then Robert Gallo warned that soon there would be no young people in virology with a holistic view of the science, and that's extremely dangerous as the world is on the brink of a new epidemic. Humanity has a short memory, it turns to scientists once every 30-40 years or so, which is the time interval between pandemics. The Great Flu (aka Spanish flu) was the 20th century's first pandemic during World War I. Then there was the polio epidemic in the 1940s-50s, and then came HIV in the 1980s.
Today, the Global Virus Network is an advisory board of scientists who are not affiliated with governments, and thus are in a position to provide an unbiased assessment of the situation to any organization on request. The GVN is a network of Centers of Excellence across the globe. It hosts seminars and advises medical professionals and scientists. That would be the function that WHO would have to perform, but unfortunately this organization has long since degenerated into a bureaucratic quagmire. This became patently clear at the onset of the pandemic, when the rules were changed and changed again many times to appease certain governments.

— Is it possible to explain why a particular pandemic occurs at a specific point in history? Some theories suggest that deadly epidemics hit a population when it becomes too numerous.
— I'm sure there are objective factors at work, associated with explosive population growth and globalization of life. But there also another factor at work here. Pandemics occur when humans invade areas where it had never set foot before. We stepped up exploration of the Far East in the 1930s, invading the depths of the taiga forests, and we ended up with a new disease, tick-borne encephalitis. Apparently, something similar happened with HIV in the 1980s. Some hunters in Africa must have killed and eaten infected monkeys. The crossing of yet another line gave us kuru disease. It turns out the disease stemmed from cannibalistic practices among the tribes of New Guinea. Kuru was transmitted in a ritual that involved eating the brain of a deceased relative at the funeral feast. As the practice of cannibalism faded away, so did the disease. Therefore, unless we learn our lessons from the current pandemic and adopt more prudent ways, we risk continued periodic recurrence of devastating tragedies.

— It sounds like an environmentalist-religious believer's view of the world.
— I'm not religious. I wasn't brought up in a religious household. Most scientists call themselves either atheists or agnostics, very few would admit they believe in God. However, many intuitively acknowledge the possibility of higher powers in the universe. When young scientists are at the outset of their intellectual evolution, they are basically a highly skilled technicians who know how to split atoms, recombine viruses, etc. At this stage it is typical for them to flirt with atheism. They may harbor the illusion that science is omnipotent. Only gradually does it dawn on them that there are things beyond the limits of the knowable, and those things are the foundation of everything. Scientists don't talk about religion, although many of them are believers, if not overly religious or church-goers. Let me give you an example from my family. It involves my wife's uncle Ilya Frank, Member of the Soviet Academy of Sciences and Nobel Prize winner in Physics. This was a world-class scientist who nonetheless believed in God and was a practicing Christian. Science and religion are not alternatives to each other, they are two different methods to study the Universe. There are three distinct concepts: faith, religion and church. You can believe in God and not be a religious person, and never go to church. Over the past two or three hundred years, the triumph of science and technology, and burgeoning belief in the seeming omnipotence of humankind have cast doubt on the existence of a higher power, promoting the rise of atheism. But if you think about it, atheism is also a religion — a religion for godelss. Some religions are polytheistic, with multiple gods, others monotheistic, with just one god, and then there are those with zero gods. There have been religious wars in which massive numbers of people died, but wars started by atheists killed even more people.

— Let's leave the pandemic alone for a while and talk about the science per se. What do you find especially interesting in virology today?
— Virology has changed dramatically since we entered this millennium, let alone the time, 50 years ago, when I first came into science. Back then, we knew very little about the genomic organization of viruses, and we had just begun to unravel their structure. We know it pretty well now. The research that has recently come to the fore looks at how viruses interact with cells, and what mechanisms they employ to invade the cell and subvert it to their ends. When new concepts emerged that provided connectivity between virology on the one side, and cellular biology and immunology on the other, followed by new physicochemical research methods, all this was tantamount to a revolution. One of the new methods, deep sequencing, has opened up incredible opportunities in virology, allowing us to study not just the full genomes of viruses, but also their subtle population structure, discovering subtle differences between seemingly identical viruses. Virus populations are a lot like a roaring crowd at a stadium. From a distance, all crowds look more or less the same. However, on closer inspection it may turn out that one crowd consists mostly of old ladies congregated to exchange houseplants, while the other is a crowd of aggressive hooligans. By examining the molecular composition of a virus population, we can make informed assumptions about its further behavior.

— How different are the "hooligans" and the "old ladies"?
— In essence, we're dealing with a cloud of very similar strains with only minor genetic differences. Yet these slight differences can dramatically affect the biological properties of the virus. Studying the genetic structure of populations offers tremendously valuable insights for understanding virus behavior.
It is often stated RNA viruses exist as quasispecies, a collection of close but genetically distinct variants. RNA viruses are a class of viruses whose genetic material is represented by an RNA molecule; Coronaviruses belong to this virus class. Once inside the human body, the SARS-CoV-2 virus that causes COVID 19 will form its own quasispecies that differs from that of the patient on the bed next to you. Sometimes subpopulations with different genome variants may occur in the same body. Molecular profiling of a viral population represents the cutting edge of science, born at the intersection of virology, molecular biology, and bioinformatics.

— But besides this, aren't viruses also studied to explore the distant past and answer questions about the origin of life? Which came first: the virus inside the cells, or the cell?
— Truth be told, no one knows how life began. One of the more widely accepted theories claims that life arose at RNA level. It is likely that at first, RNA learned to replicate itself, and then learned to create some other molecules that assisted in this process, like proteins. What would you call this primal RNA that could do nothing except replicate itself? It's nothing other than a virus. It's plausible that viruses later invented cells when they "figured" it would be a good idea to encapsulate themselves in a lipid envelope. RNA molecules learned to "live" inside this bubble, which then evolved into a cell, and then the cell began to evolve into increasingly complex structures. As a virologist, I like to think of viruses as the earliest life form. You could say that viruses were the cradle of life.
It is now a proven fact that viruses exist everywhere. Paradoxically, the biomass of all viruses on Earth is greater than the biomass of all other life forms combined, including elephants and whales. When deep sequencing and metagenomic analysis were applied to the study of seawater, it was discovered that every milliliter of water contains a vast number of viruses we never knew existed. There isn't a single organism without viruses.
Some of them travel from one body to another causing diseases, but the vast majority of them coexist peacefully with us, playing a critically important role in our physiology and evolution overall. There is no better vehicle than viruses to transmit information horizontally, body-to-body.

— Which area of virology would you personally expect to explode with new discoveries in the next 10 to 20 years?
— Niels Bohr put it this way, "It is difficult to make predictions, especially about the future". A late 19th century futurology book posed a similar question: what will be the greatest challenge for humanity in the 20th century? And gave an incredible answer: "Removal of horse manure from the streets of vastly expanded cities". Naturally, I look forward to the moment when the sheer quantity of new technology elevates virology to a new level. The emerging innovative experimental methods and the merger between disciplines, IT, and other fields will propel us to a new level where we will be equipped to elucidate some prohibitively complex biological systems and, among others, understand how the human brain works. But these are incredibly complicated matters. It makes me uneasy to discuss things I cannot fully grasp. No wonder I've devoted my whole life to viruses, which are so remarkably simple.