Oleg Glotov: ‘The first biobank in our country was opened at the University’

You were instrumental in introducing the developments of molecular genetics in predictive medicine in Russia. In your opinion, can modern science enable disease prevention through determining the likelihood of disease and to what extent? 

Yes, it can. My teacher — Professor Vladislav Baranov, a long-time leader in human genetics studies at St Petersburg University and Head of the Laboratory of Prenatal Diagnostics at the Dmitry Ott Institute for Obstetrics and Gynaecology, was the first to introduce prenatal diagnostics and predictive medicine in our country. What is the difference between prenatal diagnostics and conventional diagnostics? The key difference is that we have no right to make a mistake. Our mistakes cost dearly. They are about whether a family will have a healthy child or not. With that in mind, our teachers were extremely strict about the matters of work ethics and the attitude to diagnostics. After the introduction of prenatal diagnostics and its establishment across the country, we began to look into other ways to integrate advances of molecular genetics in public health. We continued to develop the concept of genetic passport, pioneered by Professor Baranov back in the late 1990s. Together with our colleagues, we picked up this idea and under his leadership began to implement the genetic passport in healthcare practice. At that time — in the late 1990s — early 2000s, we were the first in Russia to try to implement screening tests to identify a person’s genetic risks and recommend some predictive, i.e. preventive measures to avoid diseases. In most cases, both prevention and correction of many genetic disorders were impossible at the time. Since then, a lot has changed. Serious genetic tests are now available, such as genome sequencing and exome sequencing test in particular, which is the focus of my doctoral thesis. Today, the exome sequencing test enables us to study the human genome in depth and determine a huge number of genetic diseases. It is of paramount value, because each of us is a carrier of one or another genetic disease, or even more than one. Another thing is that we do not know what is going on in our other half, i.e. in our partner. For that reason, we are actively advocating the idea of genetic carrier screening, when a couple is tested and genetic risks are identified in advance. If such risks are determined, a number of genetic technologies can be applied help the couple have a healthy child. 

The idea, conceived more than 20 years ago, now has become revolutionary due to the availability and introduction in practice of new genetic tests. This is reflected in my thesis. The main idea, however, is that now we have a methodological tool — exome sequencing. Now, we can assess almost all genetic risks. Previously, we would talk separately about the risks of monogenic diseases and the risks of multifactorial diseases. Now, through the prism of exome sequencing approach, we can immediately assess all genetic risks of each individual. 

Your thesis topic is "Human exome sequencing and prospects for predictive medicine". Does a genetic change always mean a disease? How reliable are current genetic testing techniques in detecting future diseases? 

This is a very important question! Geneticists used to divide genetic diseases into "good" and "bad". Monogenic diseases were categorised as "good", while multifactorial diseases — as "bad" ones. It is not easy to make predictions on genetic risks; yet, taking into account the new classification of pathogenic variants in the genome, I tried to do this in my thesis. The concept change explains the correlation between the manifestation of pathogenic gene variants for monogenic diseases and their degree of pathogenicity. Professor Nikolay Timofeev-Ressovsky called these concepts "expressivity" and "penetrance", or, in other words, risk assessment in terms of severity and probability of manifestation. Let’s say, one of the parents has hereditary cardiopathy, an oligogenic disease that does not always manifest itself. We try to understand whether this genetic change in relatives will lead to a similar clinical manifestation in offspring. The probability of such manifestation is not always 100%. Environment, lifestyle and nutrition do play a role. Consequently, a DNA change does not always imply a disease. There are many concurrent factors and nuances, which emphasises the importance of genetic consultation. Hence, there are no good and bad diseases. Everything depends on the severity of manifestation of the gene variant, its expressivity and penetrance and the number of gene variants, which determines the disease. It is quite simple. 

You were instrumental in the creation of the first biobank in the Russian Federation — the Biobank at St Petersburg University. What is the value of biobanking? What is its main purpose? What opportunities do such projects offer? 

The first biobank in our country, certified in accordance with all ISO standards and requirements, was established at St Petersburg University. The Molecular Research Building at St Petersburg University was built in the late 1980s, but thanks to the foresight of our teachers, in particular Academician Sergey Inge-Vechtomov, the building was designed in such a way that it could be updated to meet the changing requirements. The University’s Biobank Centre is unique as it combines a world-class cryopreservation facility and a genomic centre. Such biobanks should be affiliated to large clinics that have genomic centres and laboratories, because they are to collect biosamples and store them properly, and then release them for various studies. Recently, one of the topical issues raised by geneticists is the availability of control samples, which can be found only in biobanks. Thankfully, in 2018, National Association of Biobanks and Biobanking Specialists was established in Russia. St Petersburg University is a member of this Association; hence, we have much more opportunities now. For biobanking specialists, such integration is of particular importance. It enables exchange of samples and joint research. Any standardisation of the protocol contributes to improving quality of research, development and implementation of approaches and techniques. Biobanking is the basis of any medical and genetic research. 

Could you please tell us about your thesis defence? Is it difficult to defend a thesis at St Petersburg University under its own terms? 

At one point, I did have some doubts. But when I read the rules carefully, I realised that there are a few important aspects: the thesis is to be translated into English; you will need a foreign reviewer; and members of the dissertation council are to meet certain criteria. But this is great, isn’t it? Opponents with an h-index only substantiate the relevance of your work by confirming that your opponent is an acknowledged expert. For instance, one of my opponents was Professor Elza Khusnutdinova, Corresponding Member of the Russian Academy of Sciences, Director of the Institute of Biochemistry and Genetics at the Ufa Federal Research Centre of the Russian Academy of Sciences. Professor Khusnutdinova is widely published overseas; her h-index is 55. Also, I was pleasantly surprised by the openness and transparency of the thesis defence procedure at the University. The procedure was simple and clear, held to a high standard. I can now recommend a public thesis defence at St Petersburg University to everyone. 

Could you tell us what advances in predictive medicine we are to expect in the near future? 

I think that we are to witness massive research effort on human exome and imminent introduction of genetic testing before pregnancy. The introduction of preconception carrier screening is important because it enables prospective parents to assess their risks of having a child with a genetic disorder. Today, genetic research has become more active all over the world, and our country is no exception. The withdrawal of major international companies from the Russian market and the policy of import substitution have stimulated domestic research and development in this field. 

Why did you choose this profession? 

My brother and I have always been interested in biology and genetics. As children we attended specialised classes at the Pioneers Palace and various other courses. Our parents had an educational background in veterinary medicine and were teaching for a long time. These also played its role. After finishing specialised physics and mathematics school No 344 and entering the University, we chose genetics because it is the most exact among the biological sciences. None others are as precise as genetics because we have all the combinations and calculations. We began studying genetics in the Department of Genetics at the University and then continued at the Dmitry Ott Institute. After classes we would go and see Professor Vladislav Baranov and Professor Tatiana Ivashchenko, my supervisor. We worked hard, and we enjoyed it. I believe that you should not just receive education, but you should also apply it real life. After all, the efficiency of the State largely relies on the economical efficiency of education system. If you have chosen a profession that does not match your interests and abilities, the state money and your time and effort will be wasted. For this reason, it is extremely important to go for what you like. I have always been and still am passionately interested in genetics. Even here, at the Paediatric Research and Clinical Centre for Infectious Diseases, as a geneticist, I re-formatted the Department of Virology into the Department of Experimental Medical Virology, Molecular Genetics and Biobanking. This is how it is called now! Currently, we have conducted an interesting basic research. I hope to publish the research findings soon. It is a very interesting study on post-COVID issues related to disease formation and genetics in children. That is to say, the genetic testing that I proposed in my doctoral thesis is universal. I emphasise, not the whole-genome sequencing test (because if we interpret the results of whole-genome sequencing test, there will be many errors), but specifically the exome sequencing test. Five years ago, when my brother and I took part in a congress on genetics in Kyoto, Japan, there was an argument: genome sequencing or exome sequencing? Complete sequences or incomplete sequences? At that time, we did not know much about it. To some extent, my work has been one of the first. Professor Vladislav Baranov was the first in the world to have proposed the 3 Ps model of predictive medicine; that is, personalised, preventive and predictive. Many people have forgotten about it, but the concept of predictive medicine was first introduced and implemented in St Petersburg. Moreover, the first Department of Genetics was established at St Petersburg University, on the initiative of Yuri Filipchenko. St Petersburg University is where genetics originated in Russia. 

What are your plans and ambitions, as a scientist? What would you like to achieve? 

At the moment, I am busy preparing a research paper for publication to report our research findings. Indeed, I do have ambitions, because I want to initiate and implement big, long-term projects. I am very happy that the Biobank Centre at St Petersburg University continues its operations. It is important that the results of your efforts continue to bear fruit, even if you moved on to other ventures. While working in Hospital No 40, I created a genetic laboratory. During the COVID-19 pandemic, I set up the largest in St Petersburg Virology Centre from scratch (we performed up to 3,500 tests per day). I initiated non-invasive screening of pregnant women, which is now a programme financially supported by the city government. Once the process has been initiated; and it is crucial to organise it in such a way that it would not halt after a change of the leader. It is very important to create a viable structure that will be able to grow and develop. I think that is exactly what happened when the University was created. We are happy to be able to say: ‘Mikhail Lomonosov, Dmitry Mendeleev, Ivan Pavlov and many others worked here...’ Inarguably, St Petersburg University holds a position of great authority. We have a great many things that make us feel proud.