— Evgeny Nikolayevich, you were born in the turbulent and uneasy post-war era [Evgeny Nikolaev was born in 1946 – editor’s note]. Could you please share how you decided to pursue a scientific career?
— It had nothing to do with my family. My mother, Alexandra Pankova, didn't even finish high school because her school years coincided with the war. My father, Nikolay Alekseevich, had a rather tragic fate. In the early days of the war, he was captured while en route from Brest to Kiev for sergeant's school. He spent nearly four years in German concentration camps and ended up in Stalin's camps upon his return home. Despite this, he later led a dignified and very fulfilling life.
I was born on December 21, 1946, on Stalin's birthday. Hence, the first toast at the table was always for Joseph Vissarionovich, and only then would we remember my birthday.

— Even though your father had been repressed?
— As a child, I lived with my grandfather, who believed that Stalin was not to blame. Like most people who had experienced the horrors of war, he revered Stalin as a god. My grandfather raised me like a soldier. He himself was called up for military service in 1942 at the age of 43, when almost all the youth had been wiped out, and was a senior officer responsible for the welfare and lives of soldiers and other officers. Such strong-willed individuals usually try to break you and enforce complete obedience. I learned to resist this at a very early age, which greatly helped me later in life because I knew how to deal with people like my grandfather.

— Who did you want to become when you were a kid?
— A bandit, I guess. In the post-war period, all children were somewhat homeless. Street upbringing resulted in an acute sense of justice, self-worth, and affiliation to a certain group. Our fathers returned with immense psychological trauma. They were busy rebuilding the country and generally didn't have time for us. Back then, I used my grandfather's surname, and my nickname was Pan. My grandparents lived in the small historic town of Lyskovo in the Gorky Oblast [currently Nizhny Novgorod Oblast – editor’s note]. Incidentally, this is where the famous Russian actor and director Sergey Bezrukov spent his childhood. That's why he was able to so accurately portray a person of such background in the TV series Law of the Lawless.

— How did you manage to overcome the influence of that environment?
— In primary school, I had an amazing teacher, Ada Lapshina (Khabel). She was evacuated from Leningrad during the siege of the city. I studied under her for the first four grades and then had to leave as my father, who had just graduated from the university, was assigned to Kstovo, a city near Gorky [currently Nizhny Novgorod – editor’s note] and the capital of the oil industry. Knowing this, she gave me a certificate with all 5's, despite my grades being all 3's. This put a lot of responsibility on me because I entered the new school as an honours student.

— Did it work?
— Yes. I was immediately appointed as the chairman of my pioneer detachment council. But my street upbringing couldn't tolerate disobedience. I started picking fights with everyone and was quickly stripped of my position. But in the new city, I keenly felt that somewhere nearby was Gorky with its special schools and pioneer palaces. And there I was, mostly playing cards with street kids — a round peg in a square hole. Hard sciences came very easily to me at school. For instance, reading Landsberg's physics textbook [Textbook of Elementary Physics – editor’s note] was enough for me to get into the Moscow Institute of Physics and Technology (MIPT). There, of course, I saw the level of students from special schools in Kiev and Moscow and realized that I had a lot to work on. In the first semester, I had all 3's and one 4. In the second semester, I had all 4's and one 5. In the third semester, I had all 5's and one 4. Now, I read lectures on mass spectrometry at MIPT's Programme in Molecular Medicine.

— Did you study with the former president of the Russian Academy of Sciences Vladimir Fortov?
— Fortov and I were almost the same age. He was a year senior and studied in a different department. But he, like me, worked at the Institute of Chemical Physics. Volodya was always well-informed. He immediately started attending a very important scientific seminar where major science leaders from the General Physics Institute and the Joint Institute for High Temperatures were giving talks. He very quickly made a career in a field closely related to the military. We knew each other from the Council of Young Scientists and the Komsomol Committee of the Institute of Chemical Physics of the USSR Academy of Sciences. We only collaborated once. He asked me to solve a problem related to so-called cold fusion, which the Americans claimed was possible. And we were the first to scientifically prove that it was a hoax. At that time, Volodya was close to the people involved in thermonuclear fusion, and I was, and hopefully still am, the only person in the country who could separate helium-3 and tritium on a mass spectrometer. Volodya gave me palladium, thought to be saturated with low-temperature thermonuclear fusion products, and asked me to measure the helium-3 and tritium content in the sample. We heated it and found no tritium or helium-3. For me, the issue was immediately settled. Some time later, the entire scientific community acknowledged it as well, so now no one is working on this topic anymore.

— How did you end up at the Institute of Chemical Physics after MIPT? Were you fortunate enough to be assigned there right away?
— In my second year, I married my fellow student. She and I both wanted to go to MIPT's Specialized Chemical Physics Department, but we got assigned to the Institute of Current Sources. Since we were not at all interested in such work, I went to the dean, Victor Talrose, and asked to join him at the Chemical Physics Institute. He asked me what my GPA was. I was almost an honours student with a 4.8 GPA. He asked me what my field of interest was, and I said physics. So he offered to study the interaction of atomic particles with solids. When I asked about other subjects, he replied that I didn't get to pick and choose. That's how things worked back then...

— You ended up working there your entire life.
— Yes. I joined his lab, spent my entire career there, became Victor Talrose’s student and later his friend, attended his funeral in San Francisco... He had a remarkable life. He voluntarily left the chemistry department to fight in the war and returned wounded... After university, he was placed under the guidance of the renowned scientist and future academician Voevodsky at the Chemical Physics Institute. During that period, the institute was tasked with conducting measurements at nuclear test sites. Talrose, for instance, was involved in the hydrogen bomb tests on Novaya Zemlya where he met Zeldovich and Khariton and formed lifelong friendships with them. In Voevodsky's lab, Talrose specialized in mass spectrometry, elevating its standards significantly throughout the country. His mentor was the great scientist and Nobel laureate Nikolay Semyonov, who developed the first mass spectrometer in the Soviet Union. Carrying on his mentor's legacy, Victor Lvovich designed several generations of mass spectrometers for chemical reaction studies, which were highly acclaimed at international exhibitions.
Upon arriving at the Chemical Physics Institute, Talrose was eager to continue the development of a radical mass spectrometer. It was a project previously overseen by George Eltenton, an English researcher invited by Semyonov. In the early 1950s, Talrose delved into methane mass spectrometry and discovered an unusual ion with a mass of 17 daltons. Then he had the audacity, as the scientific community saw it, to declare that this was a CH ₅ ⁺ ion, the existence of which contradicts the rules of valency. Nobody believed him. Fred McLafferty, an American chemist specializing in mass spectrometry, dismissed it as utter nonsense, claiming that the Russians were incapable of accurate mass measurement. However, once everyone actually saw that Talrose was right, McLafferty became his primary contact in America, introducing him to various universities and forming a lifelong friendship. Through Talrose, I also became friends with McLafferty. Fred passed away last year at the age of 98.

— Can you describe what the institute was like when you first joined it?
— It was the largest institute within the Academy of Sciences, employing 5,000 staff members. Talrose's laboratory was considered the most "physical" within the Chemical Physics Institute. In 1981, I developed an interest in ion cyclotron resonance. In 1983, we conducted a significant study at the request of Yakov Zeldovich, accurately measuring the mass differences between helium-3 and tritium. The Institute for Theoretical and Experimental Physics claimed that neutrinos had a rest mass not of zero, as Enrico Fermi had asserted, but of nearly 50 electron-volts. This intrigued Zeldovich as it could potentially explain the hidden mass of the universe, a topic he had turned to after the atomic project. Talrose then sent me in his place to a meeting with Velikhov and Zeldovich, where I pledged to separate helium-3 and tritium. We were fortunate that the Science-83 exhibition took place in 1983. There, we purchased a chemical mass spectrometer and converted it into a physical one for small masses within a month.

— Now we're getting to the crux of the matter. What exactly is mass spectrometry? And why is it so prevalent and recognized with Nobel prizes?
— It's because its application allows us to explore fundamental questions about the universe, and, most importantly, it provides answers to these questions. Since ancient times, people have been curious about the composition of the objects around us, such as water, air, fire, food, and so on. The ancient Greeks and Romans theorized that everything is made up of particles (atoms) that can combine to form different substances. However, until the 20th century, it was impossible to understand the nature, size, and properties of these particles. Technological advancements led to the creation of instruments capable of examining the structure of matter at an atomic-molecular level and at the level of elementary particles. One such instrument is the mass spectrometer, the concept of which emerged at the start of the 20th century. With its help, we can weigh individual atoms and molecules. It turns out that each type of atom (chemical element) has its own unique weight, which aids us in identifying it with high accuracy. The separation of atoms of different masses and the precise determination of these masses are carried out in electromagnetic fields, which requires the atoms to be ionized — to be transformed into charged ions (neutral atoms and molecules interact weakly with electromagnetic fields).

— What fundamental questions about the universe are scientists currently answering using mass spectrometers?
— We're investigating the composition of living organisms at the subcellular and molecular levels, as well as the composition of inanimate matter — specifically, the atmosphere of Earth and other planets, asteroids, and comets. We're also looking for traces of molecular precursors to life in space.

— How do the first spectrometers fundamentally differ from those in use today?
— In the first mass spectrometers, ionization was achieved through electric discharge. Later, a more comprehensible and reproducible method of electron impact ionization was developed. Currently, over a dozen other ionization methods are being used. In the initial devices, ions were separated by mass in a magnetic field. Today, magnetic mass spectrometers are confined to two specific areas. The first involves the precise measurement of isotope ratios in atomic physics. This task emerged during the development of the atomic bomb and the study of uranium fission, a process that was investigated by the brilliant physicist Enrico Fermi, among others. At that time, it was known that uranium had isotopes with masses of 238 and 235 [238 and 235 daltons, atomic mass units – editor’s note], but it was unclear which one was radioactive. Fermi heard from friends about a talented graduate student in Minneapolis who could separate these isotopes, so he sent him natural uranium by mail. The graduate student, Alfred Otto Carl Nier, went on to become one of the most renowned and productive mass spectrometrists. Nier separated the uranium into isotopes, and Fermi determined that uranium-235 was radioactive. This marked the beginning of the atomic bomb. The first uranium atomic bomb, which was dropped on Hiroshima, was created using a mass spectrometer known as a calutron. Nier accomplished many more things after that. For instance, the Viking mission to Mars in the 1970s carried a miniature mass spectrometer invented by Nier to analyze the atmosphere.

— Today, this method is often mentioned in relation to dating archaeological artifacts.
— That's the other area where magnetic mass spectrometers are used. Accelerator mass spectrometry is used to determine the age of archaeological finds, geological rocks, and tissues from living organisms of various historical periods. The most well-known method is radiocarbon dating. This method can determine the age of objects up to 50,000 years old with an accuracy of 15 years. Dating is done by determining the concentration of the isotope carbon-14 in a sample. Carbon-14 is formed at altitudes between 8 and 15 km and then absorbed by plants through CO₂. When a plant dies, its absorption of CO₂ stops, and the radioactive carbon-14 it contains decays and turns into nitrogen. By comparing the remaining carbon-14 in the sample to its carbon-12 and carbon-13 content, we can determine the time since the sample's carbon exchange stopped. The most famous work in this field is related to the dating of the Shroud of Turin, which was found to have been made around the 11th to 13th centuries. Last year, Novosibirsk State University in Russia acquired a Swiss-made magnetic mass spectrometer.
Another homemade mass spectrometer is operating at the Budker Institute of Nuclear Physics of the Russian Academy of Sciences in Novosibirsk. We used this mass spectrometer to measure the age of oil from the Uzon volcano caldera in Kamchatka.

— Since the end of the 20th century, mass spectrometers have been actively used to study living systems. Why haven't they been studied earlier?
— Biological systems are very complex because they consist of a huge number of different molecules, predominantly of large size, containing tens of thousands of atoms. When these are ionized through electron impact, they break down into small fragments, making it challenging to determine the original molecule from which these "fragments" originated. Moreover, the process of electron ionization requires the molecules to be vaporized and transferred into a vacuum, a feat unachievable with large molecules. The significant breakthrough occurred when we mastered the technique of ionizing large molecules without causing their disintegration.
Various methods have been developed since the 1970s, and I recall contemplating the use of secondary ion mass spectrometry for biological systems. Regrettably, my supervisors at that time failed to comprehend and see the potential in this approach.
The so-called electrospray method, credited to American John Fenn, truly revolutionized the field, earning him a Nobel Prize. In Russia, Lidiia Gall from the Institute for Analytical Instrumentation of the Russian Academy of Sciences in St. Petersburg demonstrated this possibility before Fenn, but her work went unnoticed by the global scientific community. This method typically involves dispersing biological molecules in a water-methanol solution as tiny charged droplets. As these droplets evaporate, the charges settle on the molecules without damaging them, allowing the masses of these multi-charged ions to be measured. This method has found an astounding range of applications across various fields.
For instance, I could now swipe your forehead with a cotton swab and tell you whether you had tea or coffee for breakfast, what medications you're taking, and much more based on the analysis of that swab.

— In 2011, you discovered a new method in mass spectrometry that enabled the study of previously inaccessible objects. Could you describe it?
— Indeed, we proposed new techniques for measuring mass spectra within ion cyclotron resonance mass spectrometry, a method invented by Canadians Comisarow and Marshall. In this method, we trap ions in a strong magnetic field, spin them, and then measure their mass with great precision based on their rotational frequency. Together with a graduate student, I devised and implemented a new type of ion trap for this method, which significantly improved its accuracy. Our ion trap is now incorporated into the design of the most precise mass spectrometers manufactured by the industry.

— What can be studied using these types of traps? Where are they used?
— They are used for analyzing extremely complex mixtures, like oil, for example. With such a trap, you can identify up to 300,000-400,000 different compounds in a single oil sample! Recently, we analyzed organics from lunar soil brought back in 1976 by the Soviet Luna 24 probe and ancient bitumen from an antique amphora found on the Taman Peninsula. This type of bitumen was used by the ancient Egyptians for embalming the dead centuries before our era.

— How did you start working with biological objects?
— I gradually entered this field through chirality, which is related to the question of the origin of life. The issue of chirality is the issue of living and non-living matter. What is chirality? There are objects whose mirror images cannot be superimposed on the original object through any rotations or movements. Our hands and the soles of our feet are examples of such objects. The right and left hands are mirror images of each other, but they cannot be superimposed on each other. In biology, there is a concept known as chiral purity. Almost all amino acids in living organisms, except glycine, consist of molecules with left-handed chirality. Amino acids with right-handed chirality are very rare in living systems and are only found in bacteria. However, if you artificially create amino acids using chemical synthesis methods without chiral additives, you end up with half of the molecules having left-handed chirality and the other half having right-handed chirality. This characteristic of living things was first discovered by Louis Pasteur.
Returning to our work, we developed a method to distinguish a left-handed molecule from a right-handed one on a mass spectrometer using a reference molecule of known chirality.

— Is this your most cited work?
— Yes, one of the articles on this topic is in fact my most cited paper, and there is an interesting story associated with it. One of the most successful space missions, Cassini-Huygens, was sent to Saturn's moon Titan. Long ago, American spacecraft equipped with infrared spectrometers detected the presence of amino acids on Titan. Later, it was discovered that Titan has a rich organic environment dominated by methane, which condenses due to the low temperature. On Titan, there are rivers and lakes of methane. Jonathan Lunine, a theoretical chemist with a "cosmic" surname, who I befriended while working in Tucson, Arizona, was involved in planning the mission. He noticed my work on chirality and suggested that I participate in the program. However, I didn't pass the American security clearance as the work was conducted under relatively confidential conditions. Nevertheless, we published a paper with him and Jack Beecham, a prominent American physical chemist from the California Institute of Technology, demonstrating how to measure the degree of chiral polarization on Titan using a mass spectrometer. Since there is no life on Titan, it would be extremely interesting to determine if Titan has chiral symmetry. The question is whether chiral polarization occurred on Earth because both right and left-oriented life forms emerged and then the left-oriented form became dominant and continued to reproduce, or if there is a physical chiral factor in the universe.

— Was a similar task set during the mission to the Churyumov-Gerasimenko comet?
— In the mission to the Churyumov-Gerasimenko comet, there were four mass spectrometers. Two of them descended onto the comet itself, and one was capable of conducting an analysis using chiral chromatography. However, the landing module was delivered into a crevice where sunlight couldn't reach, and unfortunately, the equipment on it failed to operate. That's unfortunate because comets generally contain a lot of organics, as has been further confirmed by recent data from mass spectrometers.
However, to "extract" comet material, it's not necessary to land on it. In the craters of the lunar polar regions, where sunlight doesn't penetrate, many comets with ice and organics have been "stored" for millions of years. So, we just need to land in one of these craters and analyze the substance there. We recently built a mass spectrometer for the polar regions of the Moon and hope that it will be in demand by space agencies.

— Now we just need to understand how to protect astronauts from harmful cosmic radiation in space.
— While this issue is not among those we've discussed, we're actively working on it as well. If we want to explore space with manned spacecraft rather than robots, we need to understand exactly what happens to the human body in space. Space factors include not only radiation but also the absence of gravity. We are actively collaborating with the Institute for Biomedical Problems of the Russian Academy of Sciences. In our first joint study, we analyzed the blood of 18 Russian cosmonauts, each of whom spent more than six months in space. We took samples before launch and after landing and examined their protein composition to see how weightlessness affects the body at a molecular level. To be honest, we weren't expecting to see any significant differences between the two blood samples. But it turned out that we were wrong. Changes occurred in all major types of cells, tissues, and organs. In weightlessness, the human body behaves as if it has been infected by an unknown agent, trying to use all possible resources for defense. This happens because we don't have any evolutionary adaptation mechanisms to weightlessness. This information is crucial as it allows us, through such research, to comprehend the specific malfunctions that lead to occupational diseases and to focus on creating drugs that inhibit these malfunctions.

— Let's transition from advanced science to practical application. Currently, it appears that the majority of work in mass spectrometry is associated with the creation of a biomarker panel for a broad range of diseases. What level of concentration can a mass spectrometer detect? How does it all actually function?
— Humans have approximately 20,300 genes. Every gene serves as a blueprint for protein synthesis. However, it turns out that certain genes can be used to synthesize multiple proteins, which in turn can undergo chemical modifications within the body, resulting in an overall production of around a million distinct proteins. This intricate molecular machinery is highly responsive to any changes occurring within our bodies. If we can understand how the body functions normally and then identify how the protein profile changes in various diseases, we will be able to diagnose diseases with high precision at their earliest stages. In essence, we are comparing blood samples from healthy individuals and patients, looking for differences in the protein profile. This profile acts like a fingerprint of the disease, enabling us to identify it through minor changes at the onset of the process. Currently, we are compiling a library of standards for quantifying the concentration profile of 1,000 proteins in blood. We are primarily focusing on non-infectious diseases such as cardiovascular disorders, diabetes, and dementia.
Without a doubt, this is one of the most crucial fields in contemporary biomedical science, and many countries are striving to invest heavily in its advancement.
The method of mass spectrometry has proven highly effective in screening newborns for genetic disorders, allowing us to use a drop of dried blood for analysis. Dried blood is becoming increasingly attractive for the search for biomarkers of various diseases. We can detect and identify approximately 800 proteins from it. This implies that doctors can send us a sample from any location without worrying about its preservation. Other areas of our work include early detection and study of Alzheimer's disease, for instance.

— How did you manage to predict the severity of SARS-CoV-2 virus and COVID-19 pandemic?
— We began working on COVID-19 last spring during the active phase of the pandemic. In August last year, we published an article on detecting and identifying the virus in scrapings using a mass spectrometer by detecting the virus's protein in the sample. The sensitivity of this method is not inferior to that of PCR, but it offers higher speed and selectivity. Additionally, this method can be used to identify any strain of the virus. We can examine around 400 samples simultaneously in just half an hour.
Another area of research focuses on devising a way to predict the severity of COVID-19 by analyzing a patient's blood. By analyzing blood drawn from a person in the intensive care unit, we can predict with 90–92% accuracy whether they will survive or not. Moreover, this can be determined on the very first day when the patient is admitted to the intensive care unit. To do that, we examine the individual's protein profile, which we have found to vary significantly among patients with different prognoses. Such techniques are necessary in the event of a total pandemic, in case we need to decide which patient should be prioritized for treatment.

— Can mass spectrometry "touch" the mind? Is there any significant research in the field of neuroscience?
— The carrier of the mind, the brain, can indeed be "touched" with mass spectrometry. We extensively worked on brain metabolomics and proteomics with Academician Alexander Potapov, who led the Burdenko National Medical Research Center of Neurosurgery, to understand which proteins are present in different brain tissues. Unfortunately, Alexander Alexandrovich passed away early last year, and the work was put on hold. We have learned to create molecular maps of healthy and glioma-affected brains using a mass spectrometer.
Another area of our brain research involves collaboration with the group of Skoltech professor Philipp Khaitovich, who studies the brain evolution of different animals and humans. We obtain mass spectrometric images of brain tissues from chimpanzees and other animals, and then compare them to humans. We are interested in whether the emergence of consciousness is associated with changes in brain structure. We want to know when and at what stage of brain development the leap occurred that separated humans from the animal kingdom.

— In which direction will mass spectrometry generally move in the next 10–20 years?
— In the same direction it has been moving already — towards ever-increasing resolution, mass accuracy, smaller dimensions, and reduced energy consumption. We hope that this will help humanity answer many fundamental questions.

— Do you think mass spectrometry will help us understand how life originated?  
— There is a concept known as anthropomorphism, the process of attributing human characteristics to certain phenomena or objects. However, there is another side to it. Our cognition is limited only by our brains, and we cannot go beyond what evolution has provided us. We think in categories "imprinted" in our brains. This is something even the ancient Greeks understood — one only needs to recall Plato's eidoi.
Scientists first encountered this when developing quantum physics to explain phenomena in the microcosm. Our consciousness, shaped by the struggle for existence, is not adapted to understand the phenomena it hasn't encountered, as they didn't affect observable life on the scale of human perception (cosmos, submicrocosm, vacuum, etc.). To overcome these anthropomorphic limitations, we need to create an overlay, which is artificial intelligence. Once we understand the nature of consciousness and equip machines with this capability, the problem will be solved.

— Does this concept have room for a Creator who created this world?
— Undoubtedly. We certainly didn't create it. By the way, "created" is also an anthropomorphism. The world is a given. Hegel believed it to be a kind of "spirit," a universal mind that was always there but existed in different forms. Nowadays, it's trendy to view the world as a giant computer operating with some excitations of vacuum, elementary particles. We are touching on deep philosophical issues that are better discussed with experts, but I don't see any of them here. Conferences on the origin of life and chiral asymmetry attract many people with mostly surreal hypotheses, but because it's impossible to verify them, they are all considered valid. So when discussing such matters, one can afford to be irresponsible.