— Since childhood, you were surrounded by science, growing up amongst scientists in Dubna, near Moscow. What was it like, and how did it shape your future decisions?
— Indeed, my childhood in Dubna was amazing. It's an experience I wish I could relive. I love that period of my life. I remember seeing many passionate and enthusiastic people at our home. They were young and always consumed by some fascinating ideas. Even as a child, I found their company to be enjoyable and stimulating. They smiled often, engaged in heated debates, and even raised their voices, although always holding a pencil in hand. They loved discussing things while strolling through the city streets. Dubna is a rather big city now; but back then, it was a small green town where most of our time was spent outside. It had a very friendly vibe and style of communication.
There is no such thing as a perfect place or era. There will always be unscrupulous people, falsifications, and theft of ideas, data, and results. However, I saw my parents' generation as a group of highly passionate physicists living at the dawn of that era. They worked diligently, knew how to foster friendships, how to love, and how to respect one another.
At one point, it occurred to me that I got into bioinformatics at a very young age, much like my father got into physics...
When I was a child, I always looked forward to seeing our guests for whom we would host parties. Our home was very welcoming. My mother loved to cook and was very good at it. The environment my parents were in was quite unique. At some point, I realized that the number of Nobel laureates who had visited our home was significantly above average.
Once, while attending a seminar at the Kurchatov Institute, I was asked who I would like to meet or talk to, and I requested Yury Kagan's phone number. They looked at me in surprise and said, "He's probably too busy, you know." And I said, "Don't worry. Either give me his number or call him yourself and mention my last name, and he can decide if he wants to talk to me." I was taken to the cafeteria for tea, and suddenly there was a stir around me. People started standing up, and I saw Yury Moiseyevich, a very elderly man of about 90, rushing towards me. I said, "Hello, Yury Moiseyevich." And he said, "Well, hello to you, Alla Lvovna." "No need to be so formal!" I replied, surprised. And he retorted "Then call me Uncle Yura, not Yury Moiseyevich." You know, things like that. He was a renowned scientist and one of my father's closest friends. Among their group of four friends ("the three Levs and Yurka") who had been close since their university days, he lived the longest. My father was the first among them to pass away.
I'm not trying to idealize the time, but there was a greater sense of refinement back then (during my youth) than there is now. Unfortunately, it's not in fashion these days. Nowadays, society places more value on money, connections, and toughness. Of course, these have always existed to some extent, but they weren't as pronounced in my family's circle. There were less vulgarities and more mutual respect. And this is not just in the realm of science, but in society at large. Sometimes, I find myself wishing for the old days.

— How did you become a bioinformatician? To find yourself at the heart of an emerging science, many circumstances need to align.
—I've had a deep love for biology, bugs, spiders, butterflies, and flowers, since I was a child. I was also drawn to physics and mathematics, which are both beautiful sciences too. In school, I was in a physics and mathematics class and found studying quite easy. Exact sciences provide structure, and help create logical connections both in life and in science, which suits my nature.
So when I learned that Moscow Engineering Physics Institute (MEPI) had a department with a biological focus, I chose this university to combine all three of my favorite sciences: biology, mathematics, and physics. Note that the third one was physics, not programming. Over time, physics was replaced by the understanding that biological data needed to be processed using a computer.
When I graduated from MEPI, we were a unique group of physics engineers with a biological inclination, although this wasn't reflected in the name of the specialty on my honors diploma. Of course, neither bioinformatics nor bioinformaticians existed at that time. And since it wasn't clear where to place us, unlike everyone else, we had free job distribution. I went to the State Research Institute of Genetics to work with Sergey Mashko, who graduated from the same department three years before me, because I understood that he had both a biological perspective, and a solid foundation in physics and mathematics.

— Just like you did. With such a background, you and your colleagues were at the forefront of modern bioinformatics. Can you describe what it was like?
— Let's begin with a fairy tale. Once upon a time, there were two sciences: chemistry and physics. And when they merged, physical chemistry and chemical physics were born. However, being an expert in chemical physics doesn't necessarily mean you're an expert in physical chemistry, and vice versa. Something similar happened with bioinformatics. The science of biology, a vast field with various sub-disciplines often referred to as life sciences, merged with mathematics and programming.

— What prompted that convergence?
— Biology began to accumulate such vast amounts of various molecular data, primarily genomic, that it became impossible to process or even store it; not just in a laboratory journal but also on a regular computer. Let me give you an example: biologists have been conducting meticulous research for approximately 15 years, which ultimately led to the creation of a genetic map of the tiny gram-positive bacterium Bacillus subtilis. By the time this work was completed, first-generation genomic sequencing technologies had emerged, and naturally, there was a strong desire to identify the full nucleotide sequence of this bacterium's genome. As you recall, the genome alphabet is made up of just four "letters" or nucleotides: A (adenine), T (thymine), G (guanine), and C (cytosine).
In 1994, I received an invitation to compete for a fellowship from the National Institute for Agricultural, Food and Environmental Research (INRAE) designed for distinguished foreign scientists. This fellowship is awarded once in a lifetime and lasts for two years. I was successful and moved to Paris, where I became part of one of INRAE's scientific teams participating in the international Bacillus subtilis sequencing project. This was a pan-European initiative involving numerous laboratories from various countries.
The bacterium's DNA contains slightly more than 4 million nucleotides. Back then, such a genome size was deemed enormous. Apart from a few exceptions, only small organisms with minuscule genomes not exceeding tens of thousands of nucleotides had been sequenced.
Thus, it posed a significant challenge. During our work, we had to develop research methods ourselves, ranging from laboratory to analytical techniques, which didn't really exist at the time. While the first software products (assemblers) were already developed by the start of the Bacillus subtilis primary genome sequence reconstruction phase, things weren't quite as straightforward when it came to the process known as gene annotation. Genome assembly isn't the ultimate goal of a genomic project; it's crucial to understand which genes constitute the genome, their relative positions, whether the genes are organized into clusters or not, their regulatory regions, what they encode, and so on. This is what annotation entails.
Believe it or not, we performed this part of the work manually. We received a massive printout of all the "letters" and scanned it visually to identify necessary structural elements, the start and end of each gene, and so forth. It was a rather tedious task, but it helped us identify patterns that were worth handing over to programmers to make the analysis simpler and more convenient.
Once each laboratory had assembled its portion of the genome, as different laboratories were responsible for different genome areas, it was time to assemble the complete genome by connecting all its parts. To illustrate the complexity of this task, let's consider another example. Imagine having numerous boxes of the same jigsaw puzzle, where the pieces form a picture of a beach segment, with the rest being blue sky and sea. Suppose all these boxes were dropped, mixing up all the puzzle pieces, resulting in many copies of the same image in one pile. The task is to recreate the original picture with the reference taken away from you and while not knowing what you're assembling. That's essentially what genome assembly is.
Colleagues also often use the analogy of a situation where several copies of the same book have been finely chopped up and you need to reconstruct its text without having access to the original. Mathematical models have proven to be absolutely essential for such work. The ideas were derived from theoretical mathematics, such as graph theory.
Around that time, the real possibility of decoding the genomes of Earth's inhabitants began to emerge, and it became clear that the conventional "office" data storage and processing tools that classical biologists were accustomed to would not suffice for us.

— Was that the moment biology, mathematics, and programming converged?
— In essence, yes. Software products that laid the foundation for the emergence of genomic bioinformatics began to appear quite rapidly. Bioinformatics is a practical science. Without challenges to solve, this science wouldn't exist.

— Were there any projects running at the same time as the Bacillus subtilis genome research?
— Indeed, there were. It was an obvious challenge that many wanted to tackle, and they did so simultaneously. Almost at the same time as the Bacillus subtilis project, a British project dedicated to studying the gram-negative bacterium Escherichia coli was launched. Around the same time in Europe and the States, two independent software packages were developed for the analysis and assembly of sequencing data. They were subsequently modified and improved as sequencing techniques and understanding of data processing advanced.

— When did bioinformatics begin to be divided into sub-disciplines?
— This happened alongside the human genome sequencing project, which spanned 30 years. The project, which received several billion dollars in funding, yielded a vast amount of data. Knowledge was accumulated about which gene is associated with certain organism properties or diseases, which mutations lead or don't lead to various problems, and much more. This data inspired practicing doctors, pharmacologists, and forensic scientists alike. For instance, it became clear that we have other unique identifiers besides fingerprints. It's possible to identify an individual based on specific short tandem repeats (STRs) in the genome, whose compositions vary among different people. Analyzing such repeats could answer questions like how many people were involved in a particular accident, potentially facilitating the search for bodies.
In agriculture, there was a tremendous interest in studying microorganisms residing in the soil. All life on Earth depends on soil health, and microorganisms, whose quantity and diversity were poorly understood, play a crucial role in maintaining its wellbeing. In the 16th century, Leonardo da Vinci said, "We know more about the movement of celestial bodies than about the soil underfoot." This statement still holds true today.
To this day, we only know about 3–5% of the microcosm around us because we can't grow the majority of bacteria in laboratory conditions. However, with the help of metagenomic analysis of soil, air, and water bacterial communities, as well as bacteria living on and inside humans and animals, etc., it has become possible to study the collective genome of a specific natural microbiota. The data gathered in this way has significantly enriched and altered the evolutionary tree of life. The wealth of information revealed different connections than those initially presented in the theory of evolution.

— So, bioinformatics not only found its place among other sciences but also transformed and reshaped many scientific fields.
— Precisely. And this process is actively gaining momentum.

— Your scientific journey continued to intertwine with projects at the forefront of bioinformatics, including the largest of them, right?
— Yes, to some extent, my personal journey to the US is linked to The Human Genome Project, the largest international project ever undertaken in biology. Although legally declared complete many years ago, this project was not essentially completed at first. It ceased to receive funding from the US National Institutes of Health, but gaps in the genome persisted. Those gaps were only filled in 2021, thanks to new high-quality sequencing technology and specially designed programs for assembling the most complex genome regions.
But when the project's funding was halted, various institutes specifically created within The Human Genome Project found themselves without tasks and started considering where to apply their know-how and resources.
The National Human Genome Research Institute in the States decided to shift its focus to mass sequencing of microbial genomes. They sequenced the first portion but did it extremely poorly, as reflected in an article with the intriguing title: “The Value of Complete Microbial Genome Sequencing (You Get What You Pay For).” They then began looking for ways to restructure the organization and invite knowledgeable people. That's how I received an invitation to the National Human Genome Research Institute.
At the institute, I established one of the world's pioneering groups that streamlined and automated the process of assembling genomic data of reference quality, or in simpler terms, of extremely high quality devoid of errors and gaps in genomes. We began to refer to this assembly stage as "finishing". This was something totally new. Something that had never been done before! In order to accomplish this task, we had to integrate lab work with the work of programmers and analysts. I've been fortunate enough in my life to find myself involved in or initiating projects that are happening for the first time. While working on my thesis, I created Russia's first expression vector for the super-production of foreign proteins in E. coli cells, which led to a series of patents. In France, I was part of a pioneering project involving the first gram-positive microorganism, which taught me a great deal. In St. Petersburg, I helped establish the first Master's program in Bioinformatics at St. Petersburg University.

— It's quite common for scientists or professionals from other fields to move from St. Petersburg to Moscow. But you did the opposite, coming to St. Petersburg and heading one of the scientific departments of the country's oldest university.
— Pavel Pevzner invited me. He won one of the first mega-grants awarded by the Russian government and established a laboratory at the Saint Petersburg Academic University, which now bears Zhores Alferov's name. This laboratory created the first version of a genomic data assembler used for sequencing a chromosome isolated from a single cell. The data obtained in this process required both specialized analysis and processing. By the time I arrived, the lab had already created and published the first version of this assembler (SPAdes).
It's quite common for academic software products to be difficult to use for anyone other than the developers themselves, as they are primarily interested in testing their approach and demonstrating its functionality, and then the developers often lose interest in the task. Users need convenience and simplicity, which is often overlooked by academic programmers who don't focus on user interfaces, manuals, and other elements necessary for user interaction with the software product. That's why I've always grumbled at brilliant mathematicians and programmers saying that their products only work in their hands. Pavel remembered this, called me, and said, "You're always criticizing us, so come to St. Petersburg and help us make the assembler user-friendly." That's how I found myself in St. Petersburg.

— Why don't academic developers think about user convenience? Is it selfishness?
— No, there is no selfishness involved. Theoretical scientists who devise new algorithms or select mathematical mechanisms for a task, test them, and ensure that everything works, feel no need to make their tools user-friendly. Especially if they aren't used immediately, right here and now, and it's generally unclear who or what they should be adapted to.
In software development companies, there are always developers who check everything thoroughly, and people who refine the product to make it user-friendly. These are all different roles. It's a waste to assign those capable of creating something fundamentally new to debugging tasks. But that doesn't mean debugging isn't necessary. For example, when you're driving a car, you don't constantly think about what's spinning and where or how everything is held together. All you need to do is open the door, get inside, start the engine, and drive. That's all that matters to you until the car breaks down. But for the driver to be comfortable, warm, and have a good view, many people had to work on it. The same applies with the tools. To make the user comfortable, various highly skilled people need to work on it.
Pavel invited me to help make their bacterial genome assembler user-friendly, so that it would be simple, convenient, and appreciated by users. I'm proud that we managed to achieve that. We were able to clearly communicate the issues users face and what they expect from the product. Without the users themselves, this would be impossible because programmers think differently and often forget that most biologists know very little about mathematics and programming. So the fewer buttons they have to press while using the program, the better.
A year later, when I was already working in Pavel Pevzner's lab at the Academic University, another American scientist, Stephen O'Brien, established a lab at St. Petersburg University with the help of another mega-grant. He knew Pavel and started persuading me to help him establish his laboratory as well. And so I found myself partly at the Academic University and partly at St. Petersburg University.

— Did you then convince Pavel Pevzner to move his lab to St. Petersburg University?
— It turned out that the mega-grant and its extension at the Academic University had ended and for some reason, the university wasn't interested in continuing to support Pavel's lab. I realized that the lab was about to be left without support, so I told Sergey Tunik, who was then the Vice Rector for Research at St. Petersburg University. He liked the idea of bioinformatics and suggested we apply for the SPbU internal mega-grant competition. We submitted a strong application, won, and the lab didn't end up in limbo. We moved it to St. Petersburg University. However, I had to choose between labs there, because at SPbU, you can't work in two labs at the same time. So I focused on the Center for Algorithmic Biotechnology. The lab matured, grew, and produced good articles. New talented people joined. New areas of study emerged. The range of software products expanded.

— In scientific circles, you're known not only as a scientist but also as an educator who nurtures and protects young scientists. Is that important to you?
— It seems to be hereditary. I got it from my father and grandfather. My grandfather on my father’s side, Joseph Lapidus, was a professor and Doctor of Medicine and Political Economy. All of it at a fairly young age, too. He was the author of several textbooks on political economy (translated into many languages) and taught at Ivanovo University. When the war started, he joined the people's militia to defend Moscow. He didn't return from the front line. There are many testimonies of his talent as a teacher from his students and colleagues, and there is a memorial plaque dedicated to him on the wall of Ivanovo University. His wife, my grandmother, was also a medical professional. They met at a medical school in Moscow.
My father, Lev Lapidus, was a physicist who worked all his life at the Joint Institute for Nuclear Research in Dubna and for many years was the youngest Deputy for Science at the Laboratory of Nuclear Problems, headed by Venedikt Dzhelepov. At that time, the lab employed about 1,500 people. My father is known as an exceptional physics teacher. He didn't teach any courses, but he was always with the youth, organizing schools and classes.
My own teaching career began when I served as the co-director of two labs, one at the Academic University and the other at St. Petersburg University. I was acutely aware of the persistent lack of bioinformaticians in the scientific field, primarily due to the fact that not many people were familiar with this discipline (despite it being 2012), and there were hardly any places to study it.
As a first step, I launched a series of open lectures on bioinformatics, which were delivered by me and my colleagues from the Dobzhansky Center every Thursday. I designed a curriculum and managed to convince my colleagues, albeit with some difficulty, to join me in this endeavor. But they did take some persuading as they didn't quite see the point of my initiative. We gave lectures in the evenings at 41 Sredny Avenue for anyone who was curious about bioinformatics — what it is exactly, why do we need it, and where it can be applied. I was expecting around three to five people to show up. However, to my surprise, the very first lecture attracted a large audience! Among the attendees were economists, philologists, journalists, and biologists. They asked very insightful questions.
I then wondered if we should offer a Bachelor's degree in bioinformatics; but realized it would be better to start with a Master's program, where students can approach their studies with more purpose. I spent a long time opposing the idea that simply adding a minor molecular biology course to the mathematics program and a minor programming course to the biology program would suffice, eliminating the need for a specialized Master's degree. Regrettably, the decision to introduce bioinformatics at SPbU hinged on these individuals' opinions.

— Did your opponents fail to recognize bioinformatics as a separate scientific discipline?
— At the time they did. Bioinformatics requires teaching critical thinking skills. Biologists are not yet ready to think in mathematical terms. Moreover, bioinformatics is not just a small component that can be incorporated into another program. It's an independent entity encompassing numerous disciplines such as data analysis and interpretation, mathematical and biological methodologies. You need to have an understanding of biology, be proficient in math, and have at least some basic programming skills. The struggle lasted for two years, but in the end the Master's program is up and running, and this year we will see our fourth cohort of students graduating.
While we were fighting for the Master's program, the idea of creating online courses on the Coursera platform emerged. At that time, it was basically the only platform for online education. Furthermore, there were very few bioinformatics courses globally, all of which were in English. Clearly, people who didn't know the language well would face significant challenges, primarily due to the vast number of unfamiliar terms. I decided to present the text in Russian and create the slides in English, allowing students to gradually familiarize themselves with the terminology and grasp the core concepts more quickly. I was able to persuade my colleagues — Mikhail Raiko, Ekaterina Chernyaeva, Nikolay Vyakhi, and Pasha Dobrynin — to join me in this endeavor. Since the launch, our course has been taken by over 200,000 people. As Pavel pointed out at the time, it was the only course on the platform (Introduction to Bioinformatics, 2014) that was created without any financial investment, purely out of enthusiasm.
We then created another course on metagenomics — a topic that remains highly relevant — but this time on the Open Education platform. Our first course also migrated to that platform.
While all of this had been accomplished abroad quite some time ago, it was a first for Russia. In the early 2010s, we were lagging about 15 years behind in bioinformatics development. Now, thanks to collective efforts, we have significantly closed this gap. Nevertheless, there is still a severe shortage of bioinformaticians, despite their salaries nearing those of programmers, a level that biologists are far from reaching.

— You were born in Dubna, worked in Moscow, France, and America, and now you're in St. Petersburg. In your opinion, where is the most comfortable environment for scientists to work?
— There were opportunities for scientists everywhere: in Dubna, Moscow, St. Petersburg, America, and Paris. You just have to want to work. However, there is no perfect place; every place has it’s drawbacks. There are places where people are reluctant to work despite having opportunities. Or people are ahead of the curve in understanding certain fields but are held back by administrators who don't understand it. Some places lack funding, while others have strict boundaries and lack freedom. Everywhere is different. I've been fortunate to consistently find myself at the forefront of something new. But it's not without its challenges... In terms of personal perception, I feel most at home in St. Petersburg. It's a city where I can breathe easily, and I always look forward to returning here.

— When I was a little girl reading about female scientists, I was fascinated by the story of Marie Curie and how radium burned a hole in her maybe only lab dress. How have you managed to balance different aspects of your life?
— I certainly have more dresses! I love stylish clothing and elegant jewelry (not necessarily expensive though). I enjoy having guests over and visiting museums and exhibitions. During my student years, we frequently went to the theater, often standing in line overnight for tickets with the entire MEPI dormitory. I love cooking, just like my mother.
However, my anamnesis leaves no doubt that I'm a workaholic. I've always worked very hard. My daughter, upon growing old enough to realize that I might not be home on weekends, would start warning me come Friday that she would fall ill if I’m not home. This is where my husband really helped me out. He and my daughter were very close friends, which was wonderful!
When my husband passed away — he, like my father, unfortunately died very young — it was a very difficult time for my daughter and me. My work was my salvation. It literally pulled me through. Without it, I'm not sure I would have coped with all of that and would have been able to help my daughter, who had lost not just a father but a friend.
My daughter, after spending a significant amount of time with me in the lab as a child, said she probably didn't want to pursue science and spend as much time behind test tubes as I did. She went on to become a successful translator, fluent in three languages. Although sometimes, she regrets not pursuing programming. She has a very structured mind.
Work is fun when you're doing something you love. However, doing a job that you find repulsive is a misery.
Perhaps Marie Curie believed that two dresses were sufficient for her. She was a highly educated person, and books about famous people can be written from various perspectives. For instance, when I read books about Landau, I can't reconcile the portrait they paint with the man I saw as a little girl at our house and whom my parents later described to me. I remember him as a stern mister who told me that in school, algebra should be learned before arithmetic. I was in elementary school and couldn't understand how it could be possible without arithmetic, so I allowed myself to disagree with him.

— What is your current goal?
— While a Master's program is a good thing, we also need other structural elements at the university such as a department or a subdivision. No Western university can afford not to have a structural unit dedicated to bioinformatics. This is indeed necessary to bring together like-minded individuals and their students.

— What qualities should a person possess to excel in bioinformatics?
— A desire to learn. To discover new things. They should have an interest in natural sciences, and a desire to understand them from within. And they shouldn't fear exact sciences.
I once had the opportunity to give a lecture to 12-year-old children. They asked such insightful questions that I thought they might stump me (but they didn't!). I was amazed by the knowledge of one boy who was interested in very relevant medical issues. When I answered his last question at the end of the session, he jumped up in his chair, threw his hands up, and exclaimed, "Now I know what I'm going to do with my life!" It's moments like these that make living and working worthwhile.

— It's always gratifying to know that your work is in demand.
— It is, especially when monitoring became a daily task and people started regularly visiting the website, sending emails, and asking questions like, "What should I do? Where should I go? What do you think?" At that point, it became clear that my work was urgently needed. I don't think a lot of scientists get to feel that. And it's incredibly gratifying. You're not just studying third-row bristles on some creature's twenty-fifth leg! You're studying something that people need right now. This has certainly been a great motivator for me in recent years.

— Is it invigorating?
— Absolutely! Every year, people ask questions that are not always easy to answer. Sometimes I have to do some additional monitoring, check foreign websites, or write to my colleagues. In short, it's not always easy and sometimes requires additional work. I try to give the most accurate answers possible because people are asking these questions out of necessity, not just out of curiosity. Even faculty members who suffer from pollinosis sometimes come and ask, "What do you think will happen tomorrow?" or "Where should I go and when?"

— By the way, what's the pollen situation like in Moscow?
— Based on our 30-year observations, the pollen season in Moscow extends by one day each year, and the intensity of pollen dispersion increases annually. The total pollen production increases by 7.7% each year. This is unfortunate news for those with allergies.

— As a palynologist, what would you suggest planting in the city to make life easier for allergy sufferers?
— That's a very good and relevant question. When they planted birch trees in Zaryadye Park and created a beautiful grove behind the GES-2, I nearly shed a tear at the thought there might be birch allergy sufferers in the House on the Embankment! Yes, birch trees are beautiful! It's a beautiful symbol of our country as well. But this is absolutely wrong in terms of allergies. In fact, in many countries with strong patient communities, there is a fight against such mindless landscape gardening. Which plants are more suitable? Primarily those that are not pollinated by the wind. Because it's the pollen from wind-pollinated plants that floats in the air and causes pollinosis. All plants whose pollen is not carried by the wind will be beneficial for people suffering from allergies. For example, rowan, which pollen is almost never found in the air. Or horse chestnuts. Or even linden trees! Although linden pollen is regularly found in the spectrum, its quantity is insignificant compared to birch or alder pollen.

— I hope one day the needs of highly allergic individuals will be taken into account. Finally, I'd like to ask if you have any grand scientific dreams.
— Speaking about aerobiology — the field closest to me — I'd love for our Moscow station not to be the only one out there. I dream of a network connected by a unified research methodology and similar, comparable equipment. It would be great if traps were installed in all cities with a population of over a million, as urban residents suffer the most from allergies. And I hope that the funding for this network comes not from private donations or scientific grants but from a state support program. That, I suppose, is my dream.