Russian medical biotechnologies – current state and development prospects

Transcript of the round table "Russian Medical Biotechnologies – current state and development prospects" organized by the National Information Center for Science and Innovation STRF.Ru .

Alexander GORDEEV, Executive Director of the Open Economy Center for Economic Research and Dissemination of Economic Information Foundation:

I suggest we start our round table. Some participants, unfortunately, are late, so we will move the agenda recorded in the program a little. The topic of our round table: "Russian medical biotechnologies – the current state and prospects of development".

To begin with, I will focus on the background. As you all know, a federal target program is being implemented, the essence of which is: financing and research of developments in priority areas. The priority direction "Living Systems" is one of the chosen ones and the second in importance and amount of funding after the National Academy of Sciences (ed. – National Association of Nanoindustry). Actually, at least – these areas are comparable in importance. The question of increasing the financing and development of "Living Systems" rests on the fact that there is no clear idea of the strategy (which areas, why and why to develop in the first place) and tactics. The fact is that "Living systems" as a priority direction, from my point of view, is absent in our country as a whole. That is, there is no comprehensive view, there is a position on its own part – doctors, agriculture, industrialists. The general concept, alas, is missing. There is an intersection, there is cooperation, there is interaction between departments, such as between the academy and the "players" in the market. Attempts are being made to somehow systematize the process and combine positions. There is no single concept. Since the market is still mainly regulated by the state (we do not yet have a normal market in this industry), the issue of coordination and drawing up a unified program is on the agenda. Therefore, the Ministry of Education and Science, Rosnauka, within the framework of the implementation of the Federal Target Program, have begun to implement their project to develop it. They are trying to bring their positions closer. It is coordinated by the Interdepartmental Analytical Center and we – the Open Economy Center.

Some steps have been taken in this direction. Quite extensive expert research was conducted, and several public discussions took place. As a result, a certain set of technological platforms appeared. The following opinion was voiced: that the "skeleton" of the future program consists of technological platforms where it will be possible to track the entire process – from research to subsequent commercialization, and it works in the competence necessary at each stage of the implementation of this process. And now consultations with representatives of relevant departments are just beginning to understand the interest and demand where these departments may intersect. The first round table was devoted to the medical direction. Negotiations were held with representatives of the Ministry of Social Health. Unfortunately, they could not be present today, but, as I understand, Valery Ivanovich Sergienko, a participant in these negotiations, knows the position of this ministry and is authorized to present it. We also have agency representatives here.

I think everyone has been given existing proposals on technology platforms. It is proposed to hold a discussion on this topic: what is there, in which direction, which platforms are prioritized, which are not, what suggestions and wishes are there from these departments, what mechanisms and ways are possible for coordinating actions. I will ask Valery Ivanovich to start his speech by voicing the position of the Ministry of Social Health. Thanks.

Valery SERGIENKO, Director of the Research Institute of Physico-Chemical Medicine, Professor, Academician of the Russian Academy of Medical Sciences:

Thank you for the honor. I didn't expect to be the first. I would like to voice the position of the Ministry of Health and Social Development, plus the Chamber of Commerce and Industry, where I am chairman of the Committee on Healthcare and Medical Industry.

Here I would like to start my speech by saying that in all the projects that are being started in our country, there are (as, probably, it should be) some general positive aspects, and there are negative ones. The positive ones are that the state has finally turned towards social policy, science, education, and allocates enough funds for this. The negative point is quite general: it lies in the fact that we still lack a systematic view of all these processes.

I will explain the essence of this thesis. Previously, it was customary to say that we have weak coordination, interdepartmental inconsistency, etc. Each department charged with developing a particular program is more suitable from its own positions than from a general view of the problem. The most striking example today is the problem with medicines, which is on everyone's lips – and which is related to the topic of this round table. We have adopted a law on medicines, a law on additional drug provision has been adopted, which prescribes a number of inconsistent positions with each other, incomprehensible to both manufacturers and scientists.

This happens because, for example, as is customary in other countries, a fundamental document has not been adopted, which in this case should be called the "national medicinal doctrine". Such a generalizing global document suggests the main directions of development in the field of drug provision: what the state is responsible for, what science is responsible for, what business is responsible for. And after that – already having such a national policy, you can create, do, write a number of laws (or by-laws) that will be aimed at its implementation. The same can be said about any other field in which we work. We do not have a "national policy" in a number of areas that would determine what is a priority, what we do not pay attention to, what we buy abroad, what we do ourselves, etc. If we talk specifically about healthcare, then we should also not forget that in addition to those programs that are being developed by the Ministry of Science, the Academy of Sciences, the Academy of Medical Sciences, there are a number of programs, so-called federal targeted ones, in which priorities have already been identified, the main accents have been placed and those areas that everyone will have to work on are shown. But, unfortunately, those federal targeted programs that are approved in the field of healthcare are not known to other departments. Only those departments that coordinate them are aware of them, and then they do not reach anyone. The main manager of financial resources is the Social Health Service. And it is clear that due to a number of circumstances, federal programs are aimed at solving absolutely specific tasks, but they lack the very section for which the Ministry of Science is responsible (the R&D section). He is either represented very insignificantly, both in the amount of funds and in the narrowness of the problems for which he is responsible. But if we look at federal programs in the field of healthcare in general, we will see just those priority points (or the demand) that must be attributed to the issue under consideration today.

Our federal target programs are presented as follows. One is called "The fight against socially significant diseases". There, as subprograms, are programs to combat STDs, arterial hypertension, diabetes mellitus, tuberculosis, oncology and a number of others. Based on the list of programs, it is possible to understand the demand for those technological platforms that we are considering today. In addition, if we talk about demand, it can also be obtained based on the analysis of morbidity and mortality specifically in our country – not all over the world. Since the health of citizens – and not the health of the population of the entire globe – we care a little more.

If we proceed from the structure of morbidity and mortality in our country, then injuries and poisoning are in the first place (unlike many other states), here technological platforms are unlikely to help us, although the option is also not excluded. In this section, the federal target program for road safety has also been developed and adopted. And there, for example, there are a number of topics in which our scientific community can participate. And nanotechnological platforms (or nanotechnological materials) can be wonderfully used in the creation of a number of means of assistance and rescue of victims on the roads. There is no doubt in anyone's mind.

Morbidity and mortality from cardiovascular diseases are in second place. Everything is clear here too. And in the field of hypertension, stroke and heart attack, our platforms can be used. I would like to note that they have an advantage over what healthcare currently has, since they allow, firstly, to carry out early diagnosis at the level of "predictive medicine". If you look at the genetic factors of predisposition to certain diseases, then based on them, you can imagine not only the structure of the current morbidity and possible mortality, but also predict what the situation will be in 5-10 years; and direct the efforts of scientists, manufacturers to look into the future and have both medicines and measurement methods and diagnostic platforms in order to prevent these diseases at a slightly different level.

If we talk about the Tuberculosis program, then it's the same here. It's no secret that today tuberculosis for our country is the main "dark spot" that covers it. The incidence of tuberculosis (and mortality from it), despite all the efforts made by doctors, has been standing still for the past 15-20 years. Despite the fact that considerable funds are being released there, it seems that new diagnostic tools and new drugs are appearing, attention has finally been paid to those tuberculosis patients who are located in places of detention. Perhaps the only shift (by 0.5 – 0.2%) occurred precisely due to the fact that these patients were treated better in prisons, they were released earlier, treated adequately, etc. What could be done in this area? I know from what has been done at our institute. Some new diagnostic platforms allow us to identify the parts of the genome responsible for the development of drug resistance, to map it not only in specific regions, but also throughout the country as a whole. Moreover, it is possible to use these techniques to [predict] the possible future drift of drug resistance that will occur with these Mycobacterium tuberculosis in 5-10 years. And this gives some prerequisites for the development of drugs against mycobacteria that do not yet exist. Accordingly, this can serve as a kind of order, first for scientists, then for the pharmaceutical industry, access to pharmacoeconomics – to strategy, to policy, to condition managerial decision-making. Such a system was created at our institute together with the Siberian Branch of the Academy of Sciences: the so-called geographical information system, in which all this information is embedded, and which, with the help of subsequent mathematical modeling, allows us to assume how the process of acquiring drug resistance of mycobacterium tuberculosis in our country will develop. In addition, these platforms are useful (those that are being made now) for studying the genome and sites responsible for drug resistance in Mycobacterium tuberculosis, which are resistant to all drugs (there are also such so–called "XDR-strains" [Ed. – extensively drug-resistance]), which concern the whole world today the world. It is clear that in order to develop a cure for these mycobacteria, it is first necessary to investigate what this drug resistance is associated with, and then how it can be defeated. If we talk about STDs, the same system was developed and is used today throughout our country. In the parent organization on this topic – TSNIKVI [ed. – The Central Research Institute of Skin and Venereology] did it simply: they made a system that allows you to "cover" the whole country with modern diagnostics (including drug resistance). Strains of microbes and bacteria that cause STDs are collected in several centers across the country, and then transferred to the central institute, where they are studied, fully characterized, and therapy is practiced specifically against these samples.

The same can be said about the hypertension program. It is clear that the consequences of atherosclerosis and hypertension – myocardial infarction and stroke - are of the greatest importance for the country, for its population, for the health of the nation. And here the technological platforms that we are talking about today can be useful in the sense that they can be used to study certain harbingers, signs, possibilities of the development of these diseases in humans. I.e., you can put prevention on a completely different level, in fact, you can study the harbingers of the disease already in newborns. With the help of medicine, it is possible to assume probabilistically (not absolutely) that this person will develop either hypertension, or a heart attack, or an oncological disease after a certain time (there are signs of this too), in order to carry out prevention from early childhood and prevent the development of the disease. This is not the prevention of infectious diseases in the style of "Wash your hands before eating." Today, on the contrary, it is advised to wash your hands no more than once a day, because with frequent washing, we wash off our protective layer, bacteria enter the body more easily.

Prevention is based on a person's genetic predisposition to the development of a particular disease. And since childhood, excluding some factors from nutrition, from communication with the environment, we can do real prevention of these diseases. And oncological ones as well. We could talk about quite a lot of things here, but I would like to emphasize once again that the structure of morbidity and mortality indicates the priorities (or the demand) that can be placed on the topic of these technologies.

Then we have oncology, followed by a lot of things, the whole pathology can be well positioned. But quite often, when they talk about the structure of morbidity, they immediately jump to the structure of mortality (which causes premature death) and forget that we still have infectious diseases in the structure of morbidity. There's no getting away from it. The diagnosis of infectious diseases is well established in our country. The issue of chemotherapy for such diseases has not been worked out in almost any way. There are, of course, some standards, broad-spectrum antibiotics, with the help of which we create drug resistance in these microbes. The platforms we are talking about today will allow us to determine exactly rational chemotherapy – to select medicines based on the study of the genetic aspects of drug resistance of specific microbes and viruses. If there are any questions later, I will, of course, answer them in the order of an exchange of views, but for now I would like to express some vision, a wish about how these technological platforms could not develop, but be implemented in the field of healthcare. With the help of a national project in this area, we have already provided the country with equipment and everything, and maybe with a tenfold margin. In my opinion, it is not always rational – in every village, in every village and district to have something of their own at the mega-modern level. Rather, the use of these modern technological platforms implies that several (8-9) centers by districts should be created throughout the country, in which, if we talk about diagnostics, then analyzes will be collected. These analyses will be carried out there, everything will be delivered to the main center. It doesn't matter where he will be – in Moscow or St. Petersburg, but he should still be alone, there should be a single place where all the information will flow. This information, of course, is not for the treatment of a specific patient – for such purposes, the information must be stored in a specific medical institution. It is intended for making managerial decisions on the development of a particular direction in healthcare. With the help of these systems, which are also one of the varieties of these technologies that we are talking about today, these issues must be resolved. To date, as I have already said (I explained this using the example of the national drug policy), we still do not have a national health development doctrine. Generally nikoy. There used to be some (one can criticize it – a bad, not bad) program for the development of healthcare until 2005. In 2005, it ended. Neither in 2006, nor in 2007, nor in 2008, by and large, neither the country, nor scientists, nor doctors know how health care will develop, what priorities will be, what the main efforts will be directed at. I.e., everything goes according to individual objects. There is no concept document in the form of a national strategy.

Perhaps I can conclude my brief statement with this. I repeat once again – since I was the first, and I didn't hear any of those present here, maybe when they speak, I will say something else, add something. Or there will be questions for me. Thanks.

Alexander GORDEEV:

Thanks. Any blitz questions? Thus, as I understand it, there are no fundamental objections to the platforms that have been listed. But the main question and the main wish is that they should be aimed at solving specific tasks. I.e. there is a gap between the topics that science studies – and if you consider that it is usually studied in academic institutions and large academies… In the course of research, we found (it's not a fact that this is correct, research is still ongoing, academic institutes at the Russian Academy of Medical Sciences have gone into medical practice) that there are almost no research institutes left. Therefore, the topic is mainly supported by a large academy, where there is a certain isolation from reality. It turns out a kind of gap. On the one hand, there are institutes and institutions of the Ministry of Social Health that practice, while losing qualifications (there were years of underfunding). And there are institutes that do science. Platforms are indeed being developed there, but they are not "sharpened" to solve specific results, for example, the treatment of those diseases that are most relevant for our country. This is where the gap happens.

What else is the problem? The existing funding programs are aimed at using the support players that exist. Therefore, there is an even bigger gap. Medicine starts financing specific tasks and goes through the purchase of imported (there are no decent offers on the Russian market). Rosnauka, etc. begins to finance, starting from basic research, and again we do not come to applied research. If we take into account that two programs are starting: firstly, on nano, where there are also quite a lot of bio-directions; secondly, Rosnauka will soon have funding for scientific programs for the development of institutes (when, in fact, innovative institutes will be created) – these application platforms will become the most relevant. On this topic, I would ask Vadim Markovich Govorun, who is also ready to speak on both nano and technological platforms, who was engaged in adapting existing platforms to the tasks that Valery Ivanovich spoke about.

Vadim GOVORUN, Head of the Laboratory of the Institute of Bioorganic Chemistry. Academicians M.M. Shemyakin and Yu.A. Ovchinnikov of the Russian Academy of Sciences:

I will try to explain (because in some sense I was the initiator of the introduction of this term "platform" instead of the simpler "technology" or some "scientific directions") why it seems to me quite relevant, especially in our conditions, and to determine what a "platform" is, at least in my understanding. Science and biotechnology are all the more so, because it is no longer exactly science, but also production, and an innovative process "in one bottle", in the field of biology is gradually becoming such a system where there are a lot of high-performance analysis methods. If earlier – in the 80s or 90s of the last century - a laboratory dealing with a particular scientific issue could afford to have several not very productive, not very expensive methods in its arsenal, today almost all biological science, which is competitive, is armed with rather expensive devices and techniques, serving more than one organization and a laboratory, and an institute and even a whole community of institutes. This is the only way there are some competitive preferences both in research and in implementation.

The platform, in my understanding, is a set of techniques and methods of devices, their connection with each other, the human potential of an institution that can be integrated or complemented with other platforms, and allows quite flexibly (depending on the current moment and the tasks that the institution faces) to solve a large range of tasks, not upgrading for a large amount of time. To clarify this, we can give an example where our country does not look very clearly. I'm talking about genomic projects that have taken place in different countries of the world since the beginning of the new century. A decisive breakthrough was achieved when new management rules were put together, new technologies were introduced, significant funds were invested in the development of devices, their installation, connection with each other – a solid information resource was attached to all this. In this case (as probably everyone present knows – at least those who work in biology), the company defeated the consortium, because the management methods, spending money, using specific equipment were significantly higher than those of everyone else. All members of the community liked it so much that many scientific institutions, including scientific ones, began to organize large centers and invest not on the principle of evenly spreading financial resources for each specific division, but on the principle of concentrating sufficiently large research capacities within these centers. Therefore, by the platform I mean a very specific set of very different phenomena, signs and material means. This includes an instrument base of a certain level; and the presence (for our country, this is especially important) of highly educated and professionally ready personnel capable of using these funds; the presence of sane tasks and certain technological reserves that allow us to develop methods that are put on this fleet of equipment, as well as the ability to adapt yesterday's scientific methods for practical needs.

It is quite obvious that in such a situation, the emergence and then development of several technological platforms causes their close interaction with each other. The competition in international markets and the complexity of the tasks that modern biotechnology faces are such that very often the solution of a problem with the help of a single platform is either not very complete or completely impossible. Since I am starting to move on to the second issue – nanobiotechnology, and there today self-assembly is considered the main phenomenon used, then there is the effect of self-assembly that has arisen in different parts of the country. Now there are no problems with communication and information exchange, certain technological platforms, which today are mainly the result of investments at the expense of public funds (but in the future, we hope, they will also come from the private sector), can be combined to effectively solve problems. It is no secret to everyone present that Russian science – if it is competitive – costs much more today than Western science, i.e. the amount of money spent on one article in Russia is more than the amount of money spent by our Western colleagues. Therefore, the creation and development of technological platforms can be quite a powerful incentive to reduce the costs that are spent on the first stages of the innovation process: research, development of methods and their rapid implementation into practice. But now let me tell you how we see the existence of technological platforms in nanobiotechnology. I'll make a reservation right away that I don't have the opportunity to talk about all nanotechnology, because to a greater extent I imagine how it can be in medical nanobiotechnology. There are some discrepancies on the agenda: somewhere medical nanobiotechnology is discussed, and somewhere the issue is more broadly…

Alexander GORDEEV:

Yes, we are talking about medical nanobiotechnology.

Vadim GOVORUN:

So, nothing supernaturally new in medical nanobiotechnology in relation to previous periods should not be invented. There are still three major sections: diagnostics, treatment methods and prevention. There is such a slang term – "nanomedicine". But in fact, this term has a very simple meaning: the use of technological advances in medicine. If they come with the prefix "nano", it turns out nanomedicine. Medicine as such, as a phenomenon, as an administrative way of managing the health of citizens has not yet been canceled and will not be canceled in the near future. Therefore, there are three major sections: diagnostics (I will talk about it mainly, because there are already quite vivid examples here), [prevention and] treatment. For economic purposes, for reasons of the fact that the population of the "golden billion" on Earth is rapidly aging, we are talking about massive preventive steps that can maintain a good quality of life for as long as possible. Maybe even increase her time [and the time when] a person remains able-bodied, etc.

There are several major sections in diagnostics. I'll start with the most difficult for this audience – this is the section dedicated to decoding biological texts. Biological texts include, in essence, all high-molecular compounds that exist in living matter: nucleic acids, proteins and other polymers that are somehow part of matter. As noted here, in the main directions, one of the largest and rapidly developing technological platforms is a platform related to the decoding of a sequence of nucleic acids. Obviously, because humanity has learned to actively manipulate this kind of molecules, and there are high expectations that nanotechnology will significantly change the cost, speed and efficiency of sequencing.

Why is this important? Because in fact, many questions about infectious pathogenesis, the pathogenesis of poorly defined genetic diseases are somehow related to DNA. And when we talk about predisposition theories, new infectious factors, and the drift of known infectious agents (viruses or bacteria), we mean that the simplest and cheapest way to implement diagnostics will be the methods of fast reading of the sequence of nucleic acids. What has been done here? Quite a long time ago, three or four years ago, a competition was announced for the human genome to cost a thousand dollars. This is a well-known fact. Technology in this direction is developing very rapidly, and already today the human genome costs not a thousand, not 20 thousand dollars, but 20 million – compared to when the first synthetic genome was sequenced – it cost three billion. There is a rapid and rapid fall in prices, the use of nanotechnological devices (nanopores, nanoparticles, nanoscale particles) for DNA fractionation, for reading, an entire direction is being formed, which can be designated "laboratory on a chip", this is a general concept, but in fact it is also applicable for reading nucleic acids.

The first major diagnostic unit and at the same time platform is a complex of biotechnological and bioinformatic methods, due to the development of nanotechnology and their arrival in biology (biotechnology); it is aimed at working more efficiently and quickly with nucleic acids, in particular decoding them. Similarly, the development of diagnostics of other macromolecules occurs. In second place are squirrels. Despite the fact that this is quite a difficult task, by now the entire proteomic community has been able to identify 5-10 thousand proteins present in the human body, and it took eight years, because the consortium has been around for years. Nevertheless, many traditional factors of containment or their implementation for the diagnosis of early stages of cancer, cardiovascular diseases are associated with the fact that the cost of determining markers independently is such that it cannot be put into practice.

Therefore, the introduction of multiparametric analysis (what is popularly called a concept that everyone hears – "biochips", but in fact – these or other solution schemes that allow analyzing proteins as markers of diseases in one test tube using particles, surfaces, a combination of these two directions, a combination of microfluidic technologies, particles and known antibodies to these factors) is seen for the next five years as an intensively developed area, certainly capable of bringing some new knowledge – and capable of bringing the diagnosis of diseases to a completely different level. Moreover, the ideology that prevails in this direction is very simple. Everyone understands that working with concentrations below the atomolar level (or femtomolar level) is extremely methodically difficult, so people try to use non-specific factors, their combinations to determine specific processes. Over the past two or three years, the number of publications where certain successes have been achieved for the early (that means the first) stage in oncology has been growing significantly more than it was in the previous time. I repeat, this became possible simply because many fairly simple devices, devices and elements that have not appeared in technology today began to be used in biotechnology.

The third parameter in diagnostics, which can be conditionally attributed to nanobiotechnology, is the presence of monitoring devices that will be combined with the body. So far I have been talking about extracorporeal devices – they are separated from humans, at least today. For diagnostics, you need to take a sample, take it to the laboratory room, process it there and then work with it. But there is a powerful direction – the so-called non-invasive or minimally invasive, where the sizes of diagnostic "robots" are microns. While they are able to analyze single parameters, the most basic ones are the pH of blood or other body media, glucose concentration. The miniaturization of technology, its compatibility with the internal environment of the body makes this direction quite promising. The development of an invasive direction and the creation of what is called "cyborg" in the scientific literature, a kind of hybrid between the human body and the introduced sensors capable of adequately registering a large number of physiologically important parameters online, as well as, possibly, further dosing of drugs, stimulating the activity of the heart muscle, if necessary, etc. Such chimeric systems – when materials science, microelectronics, and sensor technology are developing (most systems that are still compatible with the body are biosensors, chemical sensors) - look quite promising and are developing all over the world.

Another area that is underdeveloped in our country is biomems, i.e. systems that combine the properties of biological objects and objects that originate from microelectronics. Optoelectronic systems, optomechanical, electromechanical systems of the micron or submicron level are needed in order to significantly miniaturize the diagnostic direction in two ways: the direction that is associated with interaction with the internal systems of the body, and the direction associated with laboratory diagnostics. One of the main instrumental platforms in nanobiotechnology is a significant, perhaps revolutionary miniaturization of those devices that we are used to seeing on the table with the naked eye, manipulating hands, etc. If we look at this trend, then one of the significant innovations of recent times is the transition to microfluidic technologies, where biologists work with devices that have channels of 50, 10, 1 microns, with their own valves, with their own liquid supply devices, with their own analyzers built into them. The transition to systems that are absolutely integrated and autonomous (they do not require operator labor) is one time. The second is the exit of these systems beyond the scope of scientific laboratories and their gradual transfer to the bosom of use in medical diagnostics.

If we are talking about platforms that are inherent in medical nanobiotechnology, then here is what should be said. I conditionally divide it into three parts. First: living nanobiotechnology. I will talk about this in the section devoted to treatment, because viroid particles are used there, which are built on the basis of bacteria and individual proteins – this is a human attempt to copy many structures and functions inherent in living organisms by isolating something from these organisms and then recreating it through a natural process called "self-assembly". Second: semi-synthetic nanotechnology. It is more or less developed, because there are hybrids (I have already mentioned them), these are antibodies with nanoparticles, some sensors of natural or artificial origin that are placed in microfluidic systems produced by humans or robots, etc. Third (there are no publications about this part, it is little achievable or unattainable at all): complete reconstruction of analogues of living systems – cells or their functions, copying, assembly or use as diagnostic or medicinal compounds. There is a lot of talk about this, all sites dedicated to nanobiotechnology are full of futurological forecasts, but experts estimate the time to reach this level in 15-50 years. You may have to spend much more time, because today there is not even an understanding of how tightly information is packed in a live system. And in this regard, I want to give an example for biologists: the sagittal section of Escherichia coli is only two microns, the Escherichia coli genome, which has an average size of four million base pairs, has only nine megabits in the formal information scale. In fact, the amount of information that exceeds, according to the most conservative estimates, what humanity has accumulated and is stored on all electronic media. This should include a certain number of reactions that occur in the cell: chemical reactions, interactions between proteins, etc. The complexity of living systems today seems extremely high, and there is no complete understanding of how all this should happen.

Although the most daring minds (this also applies to the platform area) are trying to reproduce the living, that is, in essence, to repeat the experience that was once discussed during the revival of the homunculus. Two groups of American scientists should be included here. This is the group of George Church (George M. Church) and Craig Venter (Sgaid Venter). Venter has an approach that consists in copying mycoplasma, that is, chemically synthesizing a genome, and then by simple manipulations inserting it into a cell that is devoid of this genome and making it live. The second approach is absolutely synthetic: Church's group from Harvard University tries, empirically or theoretically determining the number of genes needed for replication, to make a genome in a chemical way as well, but in a different way; and then using the chemistry of high–molecular compounds – by creating special visicles - to try to squeeze a chemical genome into it and get some kind of life without any use living systems. The idea of reproduction is the bridge that actually lies between the current level of medical nanobiotechnology and what will happen in the next fifty years.

Now about the treatment. Everything is much simpler here, because one of the problems of treatment, which is widely discussed on various forums, reviews and predictions of futurologists, everything related to medical nanotechnology, is a simple thing. Nanoscale particles or formations for the device are able to penetrate through hematic barriers in the body, penetrate into those areas of the human body that are difficult to access for traditional medical interventions. If these particles are given a certain direction of transportation, that is, to make it targeted (and this is the main problem of modern heavy pharmacology, that is, the pharmacology of heavy drugs, which is quite toxic to the body), then it may turn out that in fact the effectiveness of the use of so-called nanodrugs can be significantly higher. Here, as in the previous section, there are a wide variety of technological platforms or techniques, of course, highly modified viral particles are used as delivery tools, they are called nanoparticles, etc. This is more of a fashion statement, because it is a well-known and well-known fact. But an alliance is developing significantly between the achievements of high-molecular chemistry, in particular the chemistry of dendrimers and what is commonly called modern medical biotechnology. This is the preparation of conjugates, for example, between antibodies and modern dendrimers to ensure their greater effectiveness. This is the creation of particles with magnetic properties for their addressing with the drug to the desired organ after instrumental diagnostics. These are all kinds of medications that are built on liposomes. Domestic achievements can also be mentioned here: under the leadership of Academician Archakov, a phospholipid liposomal preparation based on phospholincholine was made, which in itself has high activity, but is also a carrier for other physiologically active compounds. In addition, there are several corporations that simply deal with modified lipids, and liposomal or micellar topics look quite relevant in this regard.

What is new here in relation to what exists? The development of new algorithms for testing this kind of drugs is required, because unlike diagnostics, at least, which takes place outside the human body, no one yet knows and has not seriously studied safety-related aspects in relation to new generation medicines. Perhaps these are unnecessary fears, worries. On the other hand, the use of nanoparticles, the use of dendrimers, the use of other carriers or deliverers, the use of drugs that are mobilized in a certain way can cause serious complications; and there is no clear metrological or pharmacological basis for testing all this yet. Of course, issues related to the replacement of cells first, then tissues, and then organs are discussed. But it really looks like a fairly traditional, historically developing direction, since tissue cell therapy is recorded in the main directions of development, almost [as] in the program of the XXV Congress of the CPSU, and here attention will rather be paid to other issues and aspects – issues related to control. Obtaining cell lines or immortalized stem cells, their injection or transplantation into the human body does not look absolutely controversial today from the point of view not only of ethics, but also from the point of view of the safety of an individual who is subjected to this kind of manipulation. The development of the first direction is connected with diagnostics, with an increase in diagnostic power, an assessment of the mutation fund of the genomes of those cells that will be transplanted, and the antigenic background. These are the technologies when diagnostic technologies will be combined with future medicine in the field of cell technology development, cell transplantation, using them as possible prototypes of tissue organs to replace defective body functions. Everyone knows that the problem of organ transplantation is quite a serious problem, there are not enough donors catastrophically, waiting lists are very long. And great hopes are associated with the fact that this problem can be solved artificially, by taking cellular material from the individual himself, storing it and, if necessary, using it for transplantation purposes.

Thus, in medicine today, two significant problems can be identified in the field of nanotechnology. This is the problem of using chimeric compounds for delivery, for addressing, to increase efficiency and to stabilize certain drugs, we are not talking about organics, but about enzymatic drugs, antibody drugs, etc. This is quite an old story, the form of many recombinant proteins on the market since the late 90s of the last century. This is one time. The second is the development of cellular technologies in combination with the first diagnostic unit, which will make these cellular technologies safer for use. Today, the use of these technologies ends with some empirical experience, there is no such serious control over how this happens.

Finally, preventive medicine. These are cyborgs and genetic certification of the population, these are processes that are associated with the rapid and fairly effective development of platforms. The cheaper the service, the more possible it becomes to screen the population for a large number of parameters and signs. In parallel, algorithms and interpretation of these parameters are being developed. This is also not a very trivial task. And it is not so easy to interpret today in the clinic more than three or four parameters that slightly deviate from the norm (where the norm is represented by an average value with three sigma, that is, plus or minus three times), nevertheless, these algorithms are developing quite quickly, too, simply due to the fact that factual material is heating up. Preventive medicine seems to be the most promising from the point of view of life science and the development of the healthcare system, because it will allow or allows you to save a large amount of money associated with the costs of treatment. There is a direct conflict with the farm, which is interested in having more patients and that they get sick for a long time, but do not die. But, nevertheless, more or less developed countries are spending significant funds on the development of preventive medicine technology, including nanotechnology platforms. Because all the techniques that were mentioned in the first two blocks are used here: this is also a diagnosis (preferably either early diagnosis, or diagnosis of borderline conditions, or preventive diagnosis); this is the use of drugs to compensate for weak body functions, or to reserve these functions, to protect certain functions from damage; it is also an on-line diagnosis that can prevent or diagnose in time those causes that are the causes premature death or some other heavy losses that have not only social, but also economic significance. Thanks.

Alexander GORDEEV:

Thanks. Do you have any questions for the speaker?

Andrey LISITSA, Deputy Director for Scientific Work of the V.N. Orekhovich Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences:

I would like to emphasize one point that Vadim Markovich made, not as a question, but as an addition. Medical diagnostics is a sector in which existing nanoindustry products will find their application. In the short term, the introduction and commercialization of such products should be predicted in the field of medical diagnostics. I would like to draw attention to the fact that there is quite a significant groundwork here, a project related to biochips carried out on the basis of the Institute of Molecular Biology is an excellent example of a project leading to nanotechnology. Initially, these biochips were used for DNA diagnostics. However, prototypes of biochips for diagnostics at the protein level have already appeared. That is, at the proteome level. This is more informative for a number of conditions, [for example, such as] early oncological diseases. This success can be developed very simply by increasing the sensitivity of detectors, reducing the sensitivity of detectors within which the biochip is read to the level of single molecules. This is also possible due to the use of atomic force microscopy in particular, which is also quite well developed. If we talk about the short-term perspective in the field of some diagnostic solutions, this sector will bear fruit in the near future. The same cannot be said about nanocarriages (which were also mentioned), where along with positive properties (for example, these systems are able to penetrate barriers), one should not forget about the negative aspect that this same ability makes them completely unusual toxic compounds, when there is no pharmacokinetics, they accumulate in the cell and the body dies. Here's what I'd like to add.

Alexander GORDEEV:

Thanks. Any more questions?

Arseniy KAPRELYANTS, Head of the Laboratory of Biochemistry of Stress of Microorganisms of the A.N. Bach Institute of Biochemistry of the Russian Academy of Sciences:

It seemed to me that such an interesting thing as transcriptomic analysis, which is now quite developed, has not yet been heard. I have seen in the USA that literally treating doctors are trained in transcriptomic analysis methods. With the help of such techniques, you can choose a good medicine for treatment, comparing the profile of transcriptomic analyses, this can be done. Moreover, it can be done in on-line mode, so it's very interesting.

Vadim GOVORUN:

When I talked about nucleic acids, I tried to talk at all. I said that the methods of decoding nucleic acids and evaluating their activity are a fairly rapidly developing direction. I did not consider it necessary to analyze all this separately in the review speech. Of course, transcription analysis is quite actively used. At the stage of validation of lipopreparations, it is part of almost all serious platforms along with DNA sequencing methods. What can be said about its potential use in medicine as a practical tool? Unlike proteins and DNA, active transcription analysis has a number of limitations. The fact is that the protocols for taking material for this and manipulating it are somewhat different in their complexity from what is already used for proteins and DNA today. That is why in some leading centers there really are optimized schemes, when doctors and laboratory workers were able to agree on all protocols and get reproducible results. If a certain technology is invented (for example, there is MPSS technology for transcription analysis) to compare transcripts of different oncological and non-oncological cells in different states, then this technology will be as cheap and reproducible as the technology of simply determining nucleic acids; then all this will certainly come into practice. It seems to me that humanity would prefer to work with very condense material, which is nucleic acids released from the remains of the family of a potential emperor, mammoth, and anything else. A fairly stable substance. And proteins, because all the same, the effector link, with a rare special exception, the substrate that indicates the onset of the disease, are proteins or peptides, which are also quite stable. If we talk about practical proteomics, how this will be implemented is a debatable question, but the proteomic platform or a set of proteomic technologies now looks more promising, because the substrate with which proteomic technologies work is more conservative and more chemically stable. That's all.

Alexander GORDEEV:

Thanks. I want to ask Andrey Alexandrovich Ivashchenko to speak.

Andrey IVASHCHENKO, Project Manager of the HimRar CVT:

I want to show some slides. The main idea of the presentation is that Russia needs some kind of integrating target program in the field of living systems. My slides substantiate this statement.

Many of you know an interesting article by Academician Ginzburg about the physics of the XXI century, where he analyzes what breakthroughs in the XXI century in the field of physics can be expected. But it is particularly interesting that in conclusion he says (and one cannot disagree with this) that biology will be the main science in the XXI century. This is due to the fact that technologization and commercialization usually occur after fundamental discoveries. If you look at it, all the fundamental discoveries of the XX century are largely technologized, the possibilities of their technologization have been exhausted. The only discovery that claims to be fundamental is the decoding of the human genome. Therefore, all competition in the field of innovative development of mankind will probably take place in the near future in this regard, that is, in the field of living systems. After the decoding of the human genome, a competition began between developed countries to somehow technologize, patent various studies that stem from the decoding of the human genome. Despite the fact that the Nasdaq index of high–tech firms fell in 2002, the governments of developed countries have significantly expanded funding for applied research in order to reach the level of development in the field of living systems from which the industry picks them up. It is with the aim that patents for new medicines, new diagnostic systems, etc., will be held by firms located in these states, and in the next twenty years, in the international system of division of labor, it is in the field of living systems that they will occupy a certain place. There is a kind of economic intellectual war in this area. The American program, [which is led by] NIH, is Roadmap. There's a fairly old message here. Roadmap – genomic map. Now the NIH – Nation Institute of Health has invested more than four billion dollars in this program, and continues to invest intensively. A targeted network is being created that unites various laboratories, commercial organizations, and specially created data accumulation and storage centers. Many of you are aware of this program, there are a lot of grants in this area. A similar program originated in Germany, it is called the chemogenomics network. Basically, it gathers around the institutions of the Max Planck Society. Here are the years of foundation of such programs in various countries. Unfortunately, Russia is not here. If nothing happens in the coming years, we can say that in 10-15 years Russia is unlikely to occupy any significant place in the international division of labor in the field of living systems, unless the state begins to deal with this problem very intensively now.

Nanotechnology is an important direction, now consolidation has begun at least around something. It's probably right that we started talking about nano and bio right away in order to lean into this process. But, by and large, tell me, over the past twenty years, what were the fundamental discoveries in the field of nanotechnology that would provide some breakthrough technologizing phenomena? These are mainly instrumental things that will help other sciences develop, primarily living systems; and we must try to create a federal target program of living systems in Russia. You yourself know that the Ministry of Health is engaged in our living systems, the Onishchenko department is engaged in bioactive additives, and the Ministry of Education and Science is engaged in their scientific research. This activity is absolutely not synchronized at the moment, that is, there are no integrated programs that would direct all this and put efforts in one direction.

If we talk about creating a similar network of genogenomics in Russia, it is schematically depicted which technological platforms are needed to create convenient cooperation. It's a biological platform, it's robotics, it's computing capabilities, finance, a chemical platform. Here is an estimate from above, how much money should be spent for Russia in order to achieve the result that is being achieved now in the American road map program. The assessment is very simple. If they spend four billion, then we need to spend one billion, based on the fact that a year of work of a scientist there costs 300 thousand dollars, and we have 50 thousand dollars. It's not just the salary, but everything around. Although there is a big problem of efficiency, that is, thanks to the high-tech and high-speed platforms that have already been mastered in the West, the productivity of Western scientists is often higher than that of our scientists today. All these platforms are available, and with a certain state policy, they are quite easy to master. This is not higher mathematics and now it costs less money when these platforms appeared. What is important here? You know that we have created a Russian venture company, venture funds have begun to emerge, VTB (asset management fund) has been created, which has been instructed, in particular, to finance these innovative developments. Unfortunately, next year, as they said at the Venture Forum in St. Petersburg, there will be about two billion dollars of venture money on the Russian market to finance innovative developments. And the projects that are ready for this are 100 times less than it is necessary to master these two billion. In fact, we do not have seed financing, which allows us to turn scientific developments into start-up firms, which are usually venture funds and finance.

If you look at this scheme, it can be seen that for the implementation of the chemogenomics program, according to our estimates, about 400 million is needed, mainly government funding, respectively, seed funds up to $ 100 million are needed. Here, the venture sector is represented by $200 million, with 100 and 100 being the state and the private sector. The third part of venture financing has already been implemented in our country. Therefore, the question arises about the more advanced stages of knowledge technologization. There is a complicated scheme here, but look at the numbers that are on the right. This is an estimate of how much a typical transaction costs for different levels of commercialization. The sale of bio- and chemosoft is now in the region of 10 thousand dollars on a one-time basis. The sale of some services in the field of chemistry and biology is in the region of 100 thousand dollars. The sale of some already active large or small molecules is a deal in the region of a million dollars. If you have a clinical candidate, that is, a drug that has not yet started undergoing clinical trials, but has a good profile, toxicity, etc., is in the region of $ 10 million. If there is a drug that you have shown primary activity on a person, that is, you have passed the first and second phases of clinical trials (of course, these should be tests for GP – good clinical practice, as required by the FDA – Food and Drug Administration), then these are transactions in the region of $ 100 million, [available in mind] the cost of one such sale. This is an example of how commercialization can take place, at what stages and how much it costs in the field of developing new drugs or modifying old drugs, delivery conditions, etc.

It is important that this program should have a unified coordination. And basically, scientists should be present at the first stages of knowledge generation, but at the same time industry representatives should be present in a small amount in the governing bodies in order to set the vector of development. At the last stages of technologization and commercialization, the proportion should change the other way around. Basically, it should be representatives of the industry, entrepreneurs, the scientific community in the form of experts should be represented. We tried to figure out where this money could be directed – to chemistry, biology. Of course, this is mainly biology, chemistry, as well as technological, information platforms and organizational structure. An active state policy in this direction is necessary, because now there is a very strong redistribution of countries' places in the international business of "New Medicines". Generic companies from India and China have become very active, which have earned quite a lot of money, today they are starting to do what Big Pharma used to do before – they are starting to deploy research programs for drug development. This is the trend of recent years. Again, Big Pharma is not in very good condition, because in the near future many medicines will lose patent protection, and there are not enough new drugs in development, so in the coming years there will be a significant redistribution of labor in international markets and, of course, it will depend on the active role of Russia, Russian firms, whether they will receive this distribution our domestic firms, contract research organizations or not. We must take advantage of globalization, since we are forced to live in a globalized environment and compete globally. A lot of technologies can be purchased quite cheaply in the West and it is not necessary to reproduce what can be bought cheaply, for example, knockout animals or some vectors. All this is bought quite cheaply, and already based on this, the following steps are being taken, the following studies.

Here is an example of Peter the Great, before whose reign Russia lost all the wars in Europe. It took the development of new military technologies, which Peter I implemented, and then Russia turned into a large Eurasian power. The same task is now (only now there are economic wars), there is a task of rapid effective development of technologies in order to take part in these wars and in the distribution of labor. It seems to me that there is no flag bearer among people working in live systems in the Russian community right now. In nanotechnology, there is a flag carrier, there is a program. Unfortunately, there is no such flag bearer in living systems, there is no bright personality that could consolidate all the people working in this direction. Therefore, it is the right tactic to lean against nanotechnology and try to work at the expense of nano and biotechnologies and not let this branch of science, in which we all work, die. Thanks.

Alexander GORDEEV:

Thanks. As far as I understand, without having a medicinal doctrine, it is difficult to build such a network. As for the flag bearers, it's not so simple. The fact is that nanotechnology is a culture of research. By and large, there are no verticals that have already been built up with access to the market. Here we are talking about the fact that it is necessary to negotiate between sufficiently strong players. There were no strong players, there were no structured businesses, but here they are. There is a ministry, there are verticals, there is just a market and we are talking about consolidating efforts. Or we should have a flag carrier. Any questions for the speaker?

Nikolay KLIMOV, Deputy Director of the Biomedical Center (Saint Petersburg):

Your organization is called "HimRar". What is "chemical", everyone guesses, and what is "rar"?

Andrey IVASHCHENKO:

These are "chemical rarities" for short. The fact is that when the company started working, one of the main activities was the synthesis of rare reagents for catalog companies, and at that time the name arose. Rare chemical compounds were made that these catalog companies could not find anywhere in the world. So the name appeared. Now it is a high-tech Center, there are quite a lot of companies working in the field of living systems. Basically, this is preclinical drug development based on high-performance technological platforms of combinatorial chemistry, screening, reverse screening, etc.

Alexander GORDEEV:

Thanks. Any more questions?

Alexander ARSENYEV, Head of the Department of Structural Biology and Head of the Laboratory of Spectral Analysis of the Institute of Bioorganic Chemistry. Academicians M.M. Shemyakin and Yu.A. Ovchinnikov of the Russian Academy of Sciences:

Why do you think it will be cheaper with us? Our equipment is more expensive, our reagents are more expensive. If the labor of a digger is compared with the labor of a qualified excavator, then the labor of an individual Tajik is cheaper than a skilled worker. If gasoline costs so much in our country, then labor should cost accordingly to the world market. We still have state-organized barriers that make any attempts to buy something in the West much more expensive than it costs in the United States than it costs in Europe. It costs more here.

Andrey IVASHCHENKO:

I agree that under the existing circumstances it will cost more. It already costs more, and the figures are taken from 300 thousand in the USA by FTE scientists (full time equivalent) and 50-60 thousand in Russia from our practical activities. We just know in our industry, since we work as a CRO (contract research organization), then an organized place costs about that much in a circle, if it is a non-governmental organization today. But the price is growing very fast, in the USA it is also growing, but now it is already approaching the European one, where we estimate this equivalent as 100-150 thousand dollars. So this is the right question. Within the existing system, the organization of science will not be cheaper, but will be more expensive. This was also said by colleagues who spoke here.

Alexander GORDEEV:

Anyone else who wants to speak, please.

Vytautas-Juozapas Kayatono SHVYADAS, Deputy Director for Scientific Work of the A.N. Belozersky Research Institute of Physico-Chemical Biology, Deputy Dean for Scientific Work of the Faculty of Bioengineering and Bioinformatics of Lomonosov Moscow State University:

I would like to support Andrey Alexandrovich's idea about the development of chemogenomics in Russia, because there are a lot of prerequisites for this. Firstly, there is a fairly strong chemistry in Russia, the combinatorial chemistry of Russia plays a very prominent role in the world market. The second fact is that quite serious efforts in molecular modeling and software are needed here. There is also no doubt that there are very good opportunities and quite serious groundwork here. Third: bioinformatics, world bioinformatics has a significant contribution from Russia, representatives of Russia who came from Russia. This is another factor. The last thing is that this is a cumulative integral approach that can be seriously implemented in Russia. It seems to me that the idea itself that we should move in this direction is one of the platforms in the field of medical technologies.

Products that can be created. There is an ever-increasing cost of the product along the way. You can start with lower-level products, but potentially in Russia there are quite serious financial resources to invest in the creation of a large product. I think that the idea is very correct and it is impossible to linger here.

Alexander GORDEEV:

Thanks. But at the same time, as Valery Ivanovich said, there are no drug strategies. The network makes sense when it is not made for one medicine. Individual substances can be put on the market in the current conditions, even adjusted for all those logical arguments that it will not be cheaper.

Andrey IVASHCHENKO:

On the one hand, the lack of a strategy or medical doctrine is a problem. On the other hand, no, because everyone knows what medicines are needed, what is the main volume of transactions. Now oncology, diseases of the central nervous system have come out on top. It is known in which areas it is necessary to make medicines so that a license from the second phase of the clinic is bought from you for 50 million. Our firms will not be able to promote these drugs on international markets, here it is necessary to enter into alliances with Big Pharma, but at the same time to make a license to sell to the West. It is quite realistic to produce and sell innovative medicine in Russia. At the same time, it is not necessary to spend half a billion dollars on this, as organizations in the West have spent so far. This amount can be significantly reduced.

Alexander GORDEEV:

There is a position that almost all medicines are made, generics can be improved, and the best forces should be thrown at early diagnosis. There are representatives of the Federal Medical and Biological Agency and the Federal Agency for High-Tech Medical Care. Can I listen to their comments?

Maria PREOBRAZHENSKAYA, Deputy Director for Scientific Work of the G.F. Gause Research Institute for the Study of New Antibiotics of the Russian Academy of Medical Sciences:

I want to say about the fact that we only need to improve generics. The problem that is with medicines and which we will never avoid, we will not avoid, is drug resistance. It is very relevant for both infectious drugs and antitumor drugs. There is no way to do without finding new targets and creating fundamentally new drugs or finding methods to overcome resistance (and these are different approaches). These are very good state ideas that were discussed – the creation of delivery methods, the use of nanotechnology, the use of immune approaches. This is all great, but still the problem of resistance cannot be overcome. It is multiple, it can be associated with a change in the target, or it can be associated with such a simple thing that cannot be circumvented – the release of the drug from the cell. A very large and multifunctional approach is needed here, where the efforts of researchers with different psychology and different methods should cooperate, but we will not do without new drugs. And it will always be, it will not be solved now, nor in five years, nor in ten years, this is an eternal thing; because the release of the drug from the cell is a natural function of the cell, it is used to release xenobiotics. And to crush it, you will have to look for new things.

Changing the target is evolution. We can't handle that either. Therefore, one of the important problems remains the search for fundamentally new drugs based on two approaches. Molecular methods of searching for new targets are the so–called targeted drug search or targeted search for resistance development inhibitors. These areas are very relevant and we will never do without generics and improving generics. No matter how wonderful we deliver them, life will still deceive us and we will still have to look for new methods to combat it.

Alexander GORDEEV:

Thanks. More comments.

Leonid Alekseev, Deputy Director of the SSC RF "Institute of Immunology of the Federal Medical and Biological Agency of the Russian Federation":

I agree with my colleague. Of course, the creation of new medicines is an ongoing task. I think that it will always stand before humanity. And to be specific, and this is connected to a certain extent with nanotechnology, the creation of drugs, including those based on oligonucleotides, to stimulate innate immunity. There is such a failure in fact. So historically it turned out that although initially scientists were engaged in innate immunity, that is, the one that is initially available, then everyone focused on adaptive immunity, which is created after the disease or after vaccination. Now, in the modern immunological concept and in reality, this situation has been completely revised. The creation of effective drugs that would stimulate innate immunity may become the basis for solving the fight against socially significant diseases, including tuberculosis, which we have been talking about for a very long time. This is an increase in natural resistance, firstly. Secondly, there are factors among innate immunity that trigger active adaptive immunity. These things are being done very actively. Huge amounts of money are being invested in this all over the world. There is a drug SPG, but this is only one of the first swallows. A lot of money will be invested in this direction, he has great opportunities. Our Institute of Immunology is also engaged in these things.

In addition, we must not forget about another thing that we did not directly talk about – the individualization of treatment, which should be understood not only as a specific Ivanov Ivan Ivanovich, but Petrov Pyotr Petrovich should take another. This may apply to certain large ethnic groups, including those living on the territory of Russia. We know today that this is indeed the case, and in order to use certain drugs, you need to know the immunogenetic fund. Immunogenetics itself, which I have the honor to be engaged in for a very long time, has made a lot of progress today in terms of predictive medicine. Suffice it to say that with diabetes of the first type of autoimmune diseases, in the near future, apparently, this will happen with infectious diseases. It is possible to effectively predict the development of a particular disease in a particular person and again in separate ethnic groups. We know that the most diabetes in the world, a very high frequency – the Finns, in second place, unfortunately, is the Arkhangelsk region. Type I diabetes is much less common among Asian populations. Uzbeks have some immunogenetic features, they are in the first place among Asian groups. It is possible in advance, having examined the immunogenetic profile, to judge what to expect from this population in terms of the disease, etc. This also applies to infectious diseases.

There is now an opportunity (true, it's just genetics) to predict about AIDS. We know that there are groups in certain ethnic groups that will never get AIDS, but in some ethnic groups there are none. These are forecasts. Thanks.

Alexander GORDEEV:

Thanks. Last comment.

Vytautas-Juozapas Kayatono SHVYADAS:

When we talk about development, we need to keep in mind some kind of integration into the global market. In favor of the chemogenomics project, I wanted to say two short things. First: expert assessments show that the pharmaceutical market is 85% small molecules. Firstly, chemogenomics, and secondly, from the point of view of globalization and entry into the world market, the Russian combinatorial chemical business is already there. The road has already been lightened, these factors must be taken into account when we talk about development prospects. Thanks.

Alexander GORDEEV:

Our next presentation is Vladimir V. Poroikov, who will talk about bioinformatics. This question remains open to us. There were proposals to introduce bioinformatics as a separate technology platform. On the other hand, we decided that this is a tool that is necessary, and if this issue is sanctified, we will be grateful.

Vladimir POROIKOV, Deputy Director, Head of the Laboratory of Structural and Functional Design of Drugs of the V.N. Orekhovich State Research Institute of Biomedical Chemistry of the Russian Academy of Medical Sciences:

I am grateful to everyone present for the opinions expressed. In fact, my speech was provoked by the questionnaire that is on the website of a very respected foundation. But this is the previous formulation of this questionnaire, and there in the long term, that is, up to 10 years, engineering and bioinformatics were considered as promising technologies. I really wanted to say that from this questionnaire, which we have today in handouts, the term "bioinformatics" has dropped out altogether, but there is an obscure term "application of human genome data". I will try to illustrate that bioinformatics is a separate platform that just can integrate the numerous data that we have today, and tomorrow we will have even more, and for this I will move on to the next slide, which actually contains two definitions of bioinformatics: one as a scientific specialty, the second as fields of science. In fact, there are quite a lot of these definitions in the world today. Sometimes it is said that these are bioinformatic flows in living organisms, I will not consider the latter definition today. But something like the analysis of large systems of biological data using artificial intelligence seems to me a fairly reasonable definition. So, you and I know, and I will not take up your time, that within the framework of post-genomic technologies, very extensive data is accumulated that must be processed by bioinformatics methods. Just a month ago in the United States, at Harvard Medical School, [in conversation] with one of our people who make up the so-called "scientific diaspora", I was told that due to the fact that we are expected to have fast methods of sequencing genomes, we are already allocating very large arrays of genetic information, to develop efficient algorithms to work with them. But, in short, bioinformatics from this numerous information should look for markers, targets or ligands for the very moments that were reflected in Vadim Markovich's speech, that is, for diagnosis, treatment and prevention. A few years ago, there was such a paradigm – from the genome to drugs in silico. Now it seems to me that it makes sense to come to the concept of "bioinformatics as a technological platform of systems biology", and in applied terms for the same individualized or personalized medicine.

Here is one of the samples of the platform from the genome to the drug. This is a prototype that was developed under the leadership of Andrey Valeryevich Lisitsa, who is present here, when targets are identified by analyzing numerous data, which are then validated. A three-dimensional structure is isolated or modeled, ligands are searched for (the term "chemogenomics" is more popular), ligand-receptor interaction is studied, the properties of drugs are optimized in terms of their permeability through biological barriers, and in the end we get the very things that can become the final product in the form of a license for drugs. If we turn to history (I have given just a few names here, we have a fairly extensive history close to bioinformatics abroad), this list can be easily expanded if you go, for example, to the website of the Moscow Seminar on Bioinformatics, which has been led for many years by Mikhail Sergeevich Gelfand, and see the list of speakers. Not everyone is there, of course, but, nevertheless, there are quite a lot of such people. In fact, fortunately, today we also have groups that are actively working in this field, I have listed here only a part of the institutes, including the Institute of Molecular Biology, the Institute of Problems of Information Transmission, the Institute of Cytology and Genetics from Novosibirsk and so on, I will not read all this, it is important that these groups are working here and now, producing a product that finds its consumer. I will try to illustrate this with some examples, but first, I will say that in fact, the work of certain small companies is connected with Russian bioinformatics, today some of them do not exist, some are actively working – Quantum Pharmaceuticals, the Institute of Systems Biology, and some have branches in Russia, and sell their products from Canada or the USA. By the way, this is a separate topic: why it is so profitable to create a branch here, and trade from abroad. But, in fact, this is not all, in general, such firms and, I would say that the Institute of Chemical Diversity here, well, partly, may be attracted, because it is not only engaged in bioinformatics, of course, it uses these methods in its activities.

So, turning to some successful examples of developments by Russian scientists, in particular, I can say that Mikhail Sergeevich Gelfand has developed new methods for studying the regulation of bacteria, predicted new bacterial transporters, and there are publications in journals with a high impact factor. That is, at a purely fundamental academic level, in general, the work is very active. Another example from the practice of the Institute of Cytology and Genetics under the leadership of Nikolai Alexandrovich Kolchanov. Methods of potential binding sites of transcription factors, analysis of targets, in particular targets of Mycobacterium tuberculosis, are being developed. Now, for those targets that have been clarified, a certain innovative drug of combined action is being developed in order to overcome the very drug resistance, for this a certain startup company has been created in Novosibirsk. The third example is a laboratory at the Institute of Bioorganic Chemistry. Its head, Professor Efremov, is developing in silico technologies aimed at creating new drugs that act on biomembranes and membrane proteins. There are certain achievements, there are publications in prestigious journals, there are patents of the Russian Federation for antimicrobial peptides with a sufficiently pronounced antimicrobial effect. Another example from my own practice: we have created a program that predicts about 3,000 types of biological activity based only on the structure of a chemical compound. Today, this structure can be sent from anywhere in the world and get a forecast regardless of our participation, a fairly large number of people from all over the world use this service, in particular, 70,000 molecules were sent for prediction last year alone. Another example: a program developed by Professor Oleg Alekseevich Rayevsky at the Institute of Physiologically Active Substances. It is also protected by the registration certificate of the Russian Federation and last year it was licensed to one of the well-known pharmaceutical companies in the UK. The following example: Vladimir Borisovich Sulimov from Moscow State University, using computer methods, in a very short time, a class of low-molecular-weight synthetic direct thrombin inhibitors was created, which significantly surpass existing analogues. Naturally, patent applications were filed, and this was done on the basis of original molecular modeling methods developed by Vladimir Borisovich Sulimov and co-authors. There are a significant number of scientific conferences where bioinformatics specialists or those related to this issue meet and discuss all problems.

Here is just a small list of these conferences held recently. I will give one example, since it was literally in September, this is the IV International Symposium "Computer Methods in toxicology, pharmacology, including Internet resources", there is a website, you can see the details. About 200 people took part in it, they were scientists from 27 countries. The training of students and postgraduates in the field of bioinformatics is quite actively conducted, for a long time [this has been done] by the Department of Information Biology at the Faculty of Natural Sciences of Novosibirsk State University; a special course "Bioinformatics and computer design of drugs" has been conducted since 1996 at the Faculties of Biomedical Sciences; the specialty "bioinformatics" at the Department of Molecular and Biological Physics of MIPT, and finally, the Faculty of Bioengineering and Computer Science. But if we look at what is happening abroad, the number of special courses and universities in which bioinformatics is considered as a profile specialty is unusually small compared to global trends.

Now I would like to say a little about the problems. Unfortunately, they are of a general nature, they can be applied not only to bioinformatics, but also to many areas of our biomedical science and, in fact, science in general. There is a problem with the fact that there are not so many end-users of bioinformatic products and services in the country. The second problem is the lack of infrastructure. Here they talked about devices, about reagents. There is actually a bioinformatics infrastructure. It seems that this science is less expensive, that is, it requires a desk, brains, a computer connected to the Internet, but generally speaking, in order to work effectively in this area, you need access to full-text journals, you need access to electronic databases. All this is available abroad in universities and institutes. Small startups, which, as a rule, do not break away from the parental umbilical cord, these institutions use all these services. As it is easy to guess, if these startups arise in our country, then this "umbilical cord" is trying to break off, and on the other hand, the infrastructure in institutes and universities is quite poor. Since there are no such pronounced end-users, there are difficulties with business support. Until recently, the state provided support, that is, in 2005-2006, such a direction – information and communication systems – was a priority. A survey on its restoration within the framework of "living systems" is currently being considered, but 2007 has fallen out so far, no bioinformatics competitions have been announced. An important point in fact, which has the most direct relation to bioinformatics, is the problem of combining the interests of authors, organizations and investors in the commercialization of products. On the website of a very respected foundation, I recently read Marina Gordeeva's comment on the wording of the relevant code, and there, in particular, it was noted that, although there are certain advances, many issues remained unresolved.

Another problem is that, in fact, bioinformatics is a multidisciplinary field of science. This does not make it easier to understand and communicate her role to many people in our society; this is also understandable, because there is a certain barrier. Unfortunately, the same integration does not fully occur in the field of bioinformatics. Of course, in terms of commercialization, there are not enough qualified managers, nor those people who could become a bridge between fundamental science and final products. In order to ensure the sustainable development of bioinformatics in Russia, in my opinion, it is necessary to have the very infrastructure that has already been mentioned, the presence of small, medium and large projects. And in fact, all this, in principle, fits into the Procrustean bed of the Federal Target Program, which exists both from the point of view of financing and from the point of view of planned, anticipated extra-budgetary funds. What I just wanted to draw attention to is that this support should not be one-time during the year, but regular, permanent. Because if there are no small projects, then in a year or two there will be no medium, no medium, again, in a year or two there will be no large ones. There may not necessarily be large ones every year, but this whole chain of financial support should be fairly regular.

Finally, the harmonization of the interests of authors, organizations and investors plays an important role. And in return, of course, the state will receive a technological platform for both systems biology and personalized medicine, maybe even from the point of view of the definition given by Vladimir Markovich in his speech, even a set of such technological platforms. And ultimately, this will contribute to moving away from a raw-material economy to an innovative one. Thanks for attention.

Alexander GORDEEV:

Thanks. Questions?

Alexander ARSENYEV:

The question is this: for a large project, you draw the figure you expected, you predicted – 50% off-budget. It's crazy! Where will you get it?

Vladimir POROIKOV:

But are the figures different in the current state in complex projects?

Alexander GORDEEV:

No. 30%, actually.

Vladimir POROIKOV:

I'm sorry, there were up to 70%…

Alexander GORDEEV:

No, these are others, this is when commissioned by the business. There's up to 70%.

Vladimir POROIKOV:

I do not insist that the figures should be exactly like that.

Alexander GORDEEV:

As I understand it, the question is as follows: are there really such customers on the market who are ready to give 50% off-budget, for what and on what terms are they ready to do it? Do I understand correctly?

Vladimir POROIKOV:

In fact, I will have to go back to the answer given by Andrey Alexandrovich Ivashchenko and say that in the current state, when we have a clear shortage of end users of bioinformatics products and services, there are certainly difficulties with customers. In addition, in some cases, such customers, even if they have money and they are ready to invest it, try to invest it in the form of 100%, so that the results obtained as a result of the relevant research or development [go entirely] to this customer. It's also not a secret, because serious investors are not always ready to play games in priority projects with the state. So there is definitely a problem here.

Andrey IVASHCHENKO:

I have one more comment. That is, the state does seem to finance the early stages, but here is a recent innovation that appeared a year ago, when the state says that if a project is of great social importance (projects in the field of biological systems immediately get there), the state wants to be a patent holder along with the organization that, in general, won this competition. Which, in fact, completely negates the participation of commerce in such projects; because no one will make a project to then sell to a venture fund, no fund, strategic investor will buy it in order to then go to the state and it is still unclear to whom and negotiate with him as a patent holder on license payments and about something else. Therefore, if this situation is not resolved, it is highly likely that the industry will stop co-financing projects in the field of living systems within the framework of the programs that the Ministry of Science is currently conducting.

Vladimir POROIKOV:

In fact, I reflected this point in the section in which there were words about the harmonization of the interests of the authors…

Andrey IVASHCHENKO:

A year and a half ago, this was not the case. Then the state, as everywhere, as in America, reserved the rights to a non-exclusive license for the needs of the state, it did not want to be a patent applicant, did not want to be a patent holder, simply demanded that such a license be provided to it by the developer. This is a world practice…

Vladimir POROIKOV:

I would even say that four years ago, in an interview with Andrei Alexandrovich Fursenko, the idea was voiced that authors and organizations that conduct these studies should be given the opportunity to commercialize the results of scientific research, just as in America. This, of course, has a deep meaning, because commercializing something without the participation of authors, as we have often tried to do, is an unpromising occupation.

Alexander GORDEEV:

Thanks. A little help, this is really true in fact – what was said. Four years ago [it was formulated and] continues to be implemented to some extent, because there is an amendment. There are areas where, unfortunately or fortunately, living systems that are socially significant, such as national security, and so on, also fall. For these areas, by definition, the concept of joint ownership remains. Another thing is that, let's say, even the state, it is not united. There is a certain set of departments that are of state interest, and they have different points of view on a particular problem; and either one or the other point of view wins. Now the victory of that point of view begins, when from the interpretation that is understandable for business, as Andrey said, and in principle adequate, we begin to move towards active joint patenting. But I think the pendulum will go in the opposite direction. There are some eventful situations in the country that are played out this way and that, and after a while, I hope this issue will be resolved. But the problem is different: our main participants in this process are academic institutions, these are state institutions. And from the fact that they will be given these rights, they will still not be able to use them. But since we have gone to difficulties, maybe we will continue then? Arsenyev Alexander Sergeevich, I think that this will also be affected there somehow. Introduce yourself, please, we will listen…

Alexander ARSENYEV:

Yesterday I received an invitation to a conference in San Francisco, and there are two pieces of news, one good and the other bad. The good news is that this conference is on pharmaceutical outsourcing, there will be different people at this conference, from Big Pharma, from small and medium-sized businesses, from scientific organizations. And they are considering four countries where they outsource this very thing, that is, what we call a platform today, could be involved in development. China, India are the first two countries. Why is it being discussed which country is better, because it is being discussed where the most favorable rights for inventions, patents, etc. Where the investment business is favorable from this side. Then two more countries follow: these are Russia and Brazil, and although it is not very clear about the rights to inventions for some products in Russia, nevertheless, it is being considered. It is being considered, despite what the state is doing, which actually blocks the import of high-tech products, without which our direction cannot develop. It puts up some kind of protective barriers. I do not know how it does it and why, it's not my business, but in fact any reagents are one and a half to two times more expensive, equipment is one and a half to two times more expensive. How can we be competitive, at the expense of what? At the expense of brains only, at the expense of cheap wages. But if we block imports, then, most likely, we will open exports, and, most likely, our brains. We will stimulate them. That is, it is much more profitable for any pharmaceutical company to take brains from here than to create some projects here. I'm not going to talk about clinical trials – they have their own kitchen, it's all going well there. What other outsourcing business do we have? Here is the "HimRar" here. One of the things that is developing well and that is being bought is synthesis. For a number of reasons, it is cheap. The same China and the same India are competing again, and it's getting harder and harder for us. That's the first thing I wanted to say.

Secondly, diagnostics is a wonderful thing, it is necessary, because you need to know what to treat. It's not up for discussion. And this direction needs to be clearly developed. But the next question arises: and what, in fact, will we treat? I understand that HimRar makes many different chemical compounds. I visited different firms. There is a room of about 60 square meters, two robots that screen about 50,000 connections per day. One "HimRara" is not enough, but it's not a cure yet, and they cost 100 thousand, if you guessed right. How many "himrars" do we need to develop this direction in the country? Probably a lot. Do we need only one "himrara"? Probably not.

I would like to show the following slide, let's see what, in fact, we are treating, where the main medications are directed. These are mainly membrane proteins. Various representatives of these proteins are shown here. [That's what] they do: signal transmission, intercellular recognition, generation of transmembrane potential, perception of light, etc. That is, if we want to create a target, to create some kind of medicine, we must clearly know the target. How we recognize this target is another question. If we have recognized this target, we can go by the method of blunt screening. And this was done by pharmaceutical companies 10-20 years ago. They have perfected this method to the point of impossibility. Everything is robotic, 5-10 people screen hundreds of thousands of connections per day. Special cell cultures, cell lines have been bred, everything is wonderful. This method does not work, or rather it works, but very unsuccessfully. What does Big Pharma do? They are urgently rebuilding their infrastructure. I visit individual "big farms" and see a whole block of buildings being demolished, good buildings. Huge rooms are being built, filled with equipment. The heads of scientific directions are changing, because a certain new paradigm has come in this whole thing. I look at our directions, or whatever they are called – platforms, and there are questions there – up to five years, up to 10 years or more. Everything that is written here is written wonderfully, but all this, by and large, is at best today, and to a large extent it is yesterday in the global pharmaceutical business. All these directions are present there, but it's not up to five years, it's today. And they started the directions that we have just indicated here, they have already grouped together and began their structural restructuring five years ago.

What kind of money is involved in this case? The average big Pharma, its budget is 20-30 billion dollars a year. Do we have big players? And we don't have any players at all by and large. And how are we going to live? Well, let's say one of Big Pharm comes to China, builds its own outsourcing institute, in fact, a specific platform for solving specific tasks appears. Not the whole line is being built, but one platform. About 300-500 million dollars are invested under it in Shanghai. Many things are cheaper there than in Russia, and that's why she invests there, and much cheaper than in the USA. And how many people will work there? The same 400-500, that is, a million investments per person. Therefore, when we say that we have an employee worth 150-200 thousand, then we will get what we invest. In Europe, seven years ago, when some "big pharma" ordered research at the university, it cost about 150-200 thousand euros per year for one qualified person at the postdoc level. But all the infrastructure existed there: equipment – yes, reagents – yes, salary, infrastructure was already all there, so the real cost of a normal person with high productivity ... Another thing is that this person should be taken away, and not the one ... I'm talking about what we have left. There are some enthusiasts. There are some good groups, by a good account, this is an unorganized "army of King Mamai", which is trying to attack the problem in some way. I repeat once again, we have no big players, no integrators, no people who [create] all these wonderful platforms. Each of which has the right and should exist at least 5 years ago. That's who integrates them into a certain chain, who will give them orders – it's not very clear. The expectation is that Big Pharma will come. They also built so many slingshots on the way that God forbid. That is, yes, platforms are needed.

Now I would like to return to membrane proteins again. That is, today more than 50% of drugs are directed to the G-protein coupled receptor, the so-called G–BSR - that's what is sold on the market. Just two weeks ago, the structure of the beta-adrenergic receptor was released, it is also a G-protein coupled receptor, it was made at Stanford. Many Big Pharma knew about this for another six months. They are urgently changing their policy because they want to have about 1,000 different receptors in a person that are responsible for different things.

Here's a look at the top 10 medicines on the market today, they are all aimed at G-BSR. There again… This is old data, [today] it needs to be multiplied by two or three – from three billion to a billion dollars. What can we do here? Yes, we can synthesize some ligands, but in fact there is potential in Russia, and the state has invested in this potential - in laboratories, in our institute – quite a lot of money, a lot of money. I'm afraid to name the amount, but such a platform was created, it works. And this platform is aimed at creating drugs not only by screening, but when we know the spatial structure of a particular receptor protein, then we can come up with some strategy on how to create this drug, what it should be aimed at, what it should represent.

Here is such a scheme (I would say the simplest) of what we use on the platform. Here there is tyrosine kinase – these are membrane proteins, the dysfunction of which is responsible for many, many cancers, literally everything. To date, there are two ways to treat them: either we interact with an antibody from the side of the ligands, for example, and block it, or we do site phosphorylation at the bottom of the membranes. This is what is being done at our institute, we will create some interceptors that will block in the membrane region. So far, these are peptides, but maybe we can do something more stable, something more interesting. That is, yes, we have developments that may be ahead of time, but they need to be moved further in practice. And when we talk about diagnostics, it's wonderful, it's necessary, but we need to create some new ways to search for drugs, and without spatial structure, without structural biology (in a broad sense, this is X–ray diffraction analysis, this is NMR, these are molecular modeling methods, this is a very complex platform and protein expression and their refolding, a lot of things) it cannot exist without it.

Here is a prototype of the platform that we created with the money of the Ministry of Science for two years. Of course, we had a lot of groundwork, but we approached this with the help of unconventional scientific planning, an unconventional scientific organization, and it all worked. Yes, we can express; we can, if necessary, synthesize, not proteins, but some peptides; then we embed this matter in artificial membranes, this is also a developed process, these membranes have been created; then we investigate. Unfortunately, we have one physical method that allows us to obtain a structure, I would like to have other methods. And we can develop something that would really interfere in a completely conscious way in life processes. It could be a drug. This is a simple example – tyrosine kinase. In fact, we are also working with G-protein coupled receptors, that is, there are efforts. Another thing is that there are some rudiments of platforms, but someone should think and somehow create something more serious than the rudiments of platforms. Yes, Big Pharma comes to us, despite the protective barriers. Yes, we are doing some interesting projects for them, some big projects, some small ones, somewhere it is $100,000, somewhere more than $500,000, but this does not solve the country's problems. That is, there should be a big player or several players, several large institutions that should be aimed at creating drugs not in the old way, the way that existed 10-20 or even five years ago, but on new principles, using new approaches. Therefore, these approaches are, yes, more expensive, and require initial capital investments. In fact, over a long distance, they turn out to be much cheaper and much more promising. And new medicines, I assure you, will be enough to look for them for several dozen generations.

Probably almost everything I wanted to say. Now, if specifically for these platforms, I would probably remove "using knockout animals" from the last paragraph, because it restricts. A structural and functional studies… How is it with knockout animals, without knockout… Moreover, these structural and functional studies should be focused on the search for fundamentally new drugs. And once again, all these platforms are like a kind of spaghetti, unfortunately, there is no leader, an organization that would assemble something really reasonable from these individual blocks, otherwise we are simply forced to work on outsourcing. Platforms may be created, but if a single organization is not created that integrates, directs, inspires and organizes them, it will be outsourcing for Western companies, despite all the restrictions. Thanks.

Alexander GORDEEV:

Thanks. Questions?

Vladimir POROIKOV:

Alexander Sergeevich, tell me, please, how do you still see this unified organization? And where could she be?

Alexander ARSENYEV:

I could say such a simple thing. I was looking at biotechnological areas, and it reminded me of the resolution of the Central Committee of the CPSU and the Cabinet of Ministers of the USSR from 1980-some year. Literally slightly individual words have been changed. At that time, the leader and responsible for this program in the country was the Institute of Bioorganic Chemistry. I don't think the institute is able to take those areas of biotechnology and be a leader now, but I can say that the teams have been preserved, so this is the largest institute with the most developed infrastructure, with quite large investments in recent years. But it shouldn't be an institution by itself. Even then, he worked in cooperation with many other institutions and various organizations. Now business and institutes, not only academic, but also medical, which belong to the Russian Academy of Medical Sciences, should be quite closely involved in this. Unfortunately, there are practically no technological institutes left, and there are still living ones in the RAMS. I don't see any other way. We need a mutual understanding of the entire team, the participants in the process, because one team will not pull it, even such a large one as the Institute of Bioorganic Chemistry.

Vytautas-Juozapas Kayatono SHVYADAS:

Why don't you like the idea of complex projects or super projects that are clearly directed and have this kind of research in mind?

Alexander ARSENYEV:

I like complex projects, but at best they solve the tasks of a separate platform – at best. We are talking about the vision of the farthest perspective and how to create something really working from these disparate blocks. Because each individual block, no matter how good it is, will not be able to produce that semi-product that costs $100 million, at best it will end up at $100,000.

Vytautas-Juozapas Kayatono SHVYADAS:

In fact, it is a question of how to develop these projects further. Not just to give them, but to watch them in development, in the long term.

Alexander GORDEEV:

But that's exactly what it's worth. Because, as practice has shown, complex projects allow at best to reach the level of medium-sized businesses. And then, most likely, in the absence of infrastructure, they remain at the small level. It is necessary, as you say, for business to be involved. I fully support those positive characteristics of IBH and imagine its size; do you imagine what size a business should be that would be above this organization? Or will it be a large number of small businesses? Anyway, you will not create an industry, you will create big pharma on outsourcing – not the one [that is], but the second way, which is now trying to be developed. I do not know when a high-tech company starts growing at the level of a serious institute, where there are developments, after a while at the level of big pharma. But there are a lot of contradictions here, because the organization, interdepartmental fragmentation, and so on. And, unfortunately, it will be very difficult to reach some kind of consensus (and it will have to be sought between specific players).

Here is an experiment (because, again, a consensus was found) going to the State Genetics Institute. Business comes in there, and now they are doing a megaproject, maybe there will be some kind of IPO at the exit. In fact, I would ask Olga Anatolyevna Lesina to comment.

And according to the regulations. Let's not interrupt. There is tea and coffee there, you can bring it here and drink it, and at the end discuss it, because breaks when discussions begin lead to fatal consequences for the discussion. Therefore, I suggest we stay a little longer and finish early, we will have two speakers. Olga Anatolyevna is responsible for the program here…

Andrey Lisitsa:

It seems to me that there are things that are reasonable, but which are practically unattainable in these specific circumstances. This is often referred to as missed opportunities. That is, yes, it would have to be done, but for some reason it does not coalesce. It seems to me that yes, we have come a long way from very small projects, when the ministry gave out a million – and the team was happy. We have grown to 100-120 million in projects, we have grown to megaprojects. And we need to think further on how to organize it. There are different possibilities, there are different options, but they need to be worked out right now. And society should treat this normally, understand that one or the other leader will still appear. Or several leaders, or players…

Alexander GORDEEV:

No, actually, I won't agree. Just a second. We have grown up to megaprojects. But the thing is that we are stuck, we have eaten all the available FSUEs that can be commercialized, because they are non-governmental institutions. We have Prometheus, Saturn, Debabov and Adeev – everything. And it did not go massively, because further along the living systems they rested on the fact that the rest are state institutions, no one will come there, no business will enter there. And even at the current stage, when the institution cannot engage in any activity other than services, cannot commercialize anything from the accumulated property – this is the problem. Then the mechanism broke down, because RVC was being created, it had to pick up and grow further companies. Therefore, we have not exhausted the megaprojects, we have stood up, we have exhausted the participants…

Vytautas-Juozapas Kayatono SHVYADAS:

Alexander Sergeevich and Vadim Markovich mentioned earlier that cadres occupy an important place in platforms. And of course, we know that our Russian personnel are quite competitive on the world market. There are many examples of this. There are a number of countries that focus on Russian scientific personnel, and we still have a very great interest in studying in this field - natural sciences. In particular, at our Faculty of Bioengineering and Bioinformatics, the competition is 13 people per place. We have a good choice. But if we want these cadres – because they are potentially strong – to really work, then we should not give them work with generics, because no one will be carried away by this, they will never stay in the country to solve this type of issues, large-scale tasks are needed. In this sense, Alexander Sergeyevich is very right that those tasks should be connected with financing mechanisms.

It seems to me that one of the problems is that there are no candidates for megaprojects. But there is a certain discrepancy here: if our support mechanism does not correspond to the participants, then the disorder in the system is quite large, because we have to "play" with our participants. The system should fit the capabilities that we have, and the tasks that we can set not theoretically, but really. There seems to be a discrepancy somewhere between the capabilities of our scientific community and the support mechanism. Probably, here we still need to look for more reasonable and accessible mechanisms that would not require us to bring reports for the second year of the project.

Alexander GORDEEV:

I absolutely agree with you. Here the question is in the system – there are potentially participants, they are not from the point of view of the system and from the point of view of management models. If we consider that there is a contact of the institute – the same SSC, in those niches where they have been preserved. Gazprom, RAO UES – they have their own institutions, they are supported from [their] point of view, but in fact, from the point of view of Rosnauka and the program, [this support] is not effective enough. This is my position. There is money there. If we say that we are changing the structure of the economy, then we are entering a niche where there are actually no businesses or players – they need to be created. And, as practice has shown, after the branch of science is no longer in these niches, the only thing from which it can be grown is academic institutions that have survived and have a strong applied component. It's still scattered. There is also an ideology of LLC: it was grown at the laboratory level. [It is necessary] to grow something big out of this, because there are a lot of developments, but on the other hand, there are managerial tasks. So it is difficult to solve the issue – there is departmental disunity. Departments, instead of agreeing on these specific cases, solve their problems.

Olga LESINA, Head of the Department of Programs and Projects of the Federal Agency for Science and Innovation:

In fact, I just wanted to add a little and say that Rosnauka and other departments tried to continue the line of the previous program in the new program. And if then two billion (or a little more) were released for the priority direction "living systems" in 2005-2006, then the new program for 2007 indicated an amount of 2.6 billion, in the future it increases – 3.5 billion were released for 2008, 4.5 billion in 2009, then 5.7 billion, and somewhere by 2012, the total comes out at 8.5 billion. In total, about 30 billion rubles will be allocated for the priority direction "living systems" within the framework of the program. The amount is quite significant. It will allow you to develop any directions. Moreover, as it was said, the program uses different mechanisms. If the first block, which is problem-oriented on search research and involves the creation of scientific and technical groundwork, provides support for search research, international projects of leading scientific schools. Within the framework of technology development, where complex projects are being implemented, development work is being supported. For us (and for everyone), what is new from this year is the commercialization of technologies in the third block. In addition to the continuation of VIP projects - where, as it was correctly said, GosNIIgenetics participates this year, there are also new events related to development projects conducted on the initiative of the business community. They are carried out under the tasks of technology implementation and product release. Large extra-budgetary funds are spent on them. If event 2.7 is 50%, then event 3.2, where production is already implied, has up to 70% of extra–budgetary funds. We are also somehow rebuilding, trying to support the technologies that society needs.

I would like to note that on Tuesday we have already posted new information maps and new requirements for the formation of topics for 2008-2010, taking into account the limitations in the program. We will give two years and up to 10 million for exploratory research, 2-3 years for experimental design. Please note, there was a change to resolution No. 531: from 30 million rubles are released for experimental design research, because there were many comments from the series - if search engines have 10 million, then design should go from 50 million. It was difficult for some organizations to overcome so many costs, so the amount has been reduced. Please send your suggestions. I hope that the state somehow supports the development of science within the framework of "living systems".

Alexander GORDEEV:

Thanks. This just says that there are no major projects. And the question, as far as I understand, is not that it is difficult to attract co-financing. More critical is the fact that in two years it is necessary to issue a mountain and start selling all this. Under the condition of a normal division and consideration of rights to results, money would be more willing to invest in five-year programs. In the current current legislation, it is only possible to seek compromises by negotiating between the players. Because there is estimated funding for the Academy of Sciences, they have their own programs (they reach a certain stage). And then these collectives could be picked up by the current federal program, where there is also a piece with knowledge generation. Then, probably, it would be possible to grow some kind of joint platforms until changes are made to the legislation. No one will create powerful institutions now, unfortunately, because they are simply not registered. Unfortunately, they are outside the rules of the game. Therefore, only compromises remain. Yes, and please, just please introduce yourself for the transcript.

Vadim IVANOV, Director of the Institute of Bioorganic Chemistry. Academicians M.M. Shemyakin and Yu.A. Ovchinnikov of the Russian Academy of Sciences:

Vadim Tikhonovich Ivanov, Institute of Bioorganic Chemistry (he has already been mentioned several times).

We came close to talking about what the vision of the situation is, what we would like to have with a greater or lesser degree of probability, according to the possibilities. Firstly, I will say that we would very much like to have our own big pharma – there is no end user. It's true. It was said that there are very big difficulties when we try to organize some conglomerates. Nevertheless, I am convinced that the need for them is ripe, and I raised the question that we need our own public-private corporation. What is it called now?

Alexander GORDEEV:

Public-private partnership.

Vadim IVANOV:

Public-private partnership, right. It just needs to be done, with all the difficulties that you have convincingly talked about. This, of course, should include former applied institutes; although they are badly destroyed, there are still some personnel left, there are some opportunities. I think many people think so. Even, as far as I know, steps have been taken in the Ministry of Industry. I don't know how they ended, but such an initiative was shown. Here you need to find a way to bring it to some kind of implementation. There should be a beginning, even if with disadvantages. It would be a prototype of the interaction of the scientific community with big business.

The second point: there is a big problem from our experience when we are trying to work in the field of creating new medicines. We find some interesting ideas, we have the first results and groundwork. There are substances with a unique set of properties that are promising for further development. We win grants from the Ministry of Science to do just the production technology and the primary stage of testing (these may be animal toxicity tests, preclinical tests, roughly speaking). As for the next stage – a real drug trial, this no longer concerns the Ministry of Science, but directly the Ministry of Health. In fact, the support opportunities here are exhausted at the first stages, and everything ends. Is it possible (I think it would be very cool) for representatives of the two ministries to meet and agree on the creation of some kind of financing system from two sources, a program to create new medicines - from beginning to end? Maybe not from the very beginning (there must be some groundwork before the start of the project). Nevertheless, the ministries should join forces in financing whole projects, not partial ones. This is my deep conviction. That would really be a new step. The only question is the desire of the representatives of the ministries to talk to each other, to look for some joint solutions. This thing would deserve to be discussed in some circles (not here, since it should be decided at the highest level).

The third consideration that has arisen in the course of what I have heard here. Vadim Markovich (and not only him) spoke about one pressing problem: how to determine what can be attributed in the field of biotechnology to nano-research, and what is irrelevant. In general, the very formulation of the question – "what is possible and what is not" – amuses me somewhat. We're not doing philology! And not by classification. It is clear that it arose due to the fact that "nano" will be funded, and "non-nano" will not be funded. That is, regardless of how original, promising and significant the development is, funding will be based on the fact whether it belongs to the field of nanotechnology or not. That's all I wanted to say.

Alexander GORDEEV:

Let's start with the simplest – the interaction of the Ministry of Science and the Ministry of Health. It has already begun, in fact: the round table and subsequent negotiations launched this process.

Then there is a second question (simpler) about what would be attributed to "nano"? I don't know how Rosnanotech will develop. There, in fact, the following idea has been implemented: budget money becomes extra-budgetary. They do not "hang" because there are quite a lot of restrictions on programs. A year has passed – you need to report. It is impossible to develop normal projects where the return will be in 3-5 years. Unfortunately, we still have an annual quantum. On the other hand, nanotechnology will not be able to spend money on anything where there is no prefix "nano", and therefore there is some kind of logical link. This term has gone.

A more difficult question arises if we take into account what you said about Big Pharma. Pharmaceutical enterprises have lost their research centers – they are not there. Of those enterprises that exist now, and who Rosprom is engaged in, trying to combine something, there is almost no scientific component left. If we go back to the fact that we are restoring science and reaching some results ... the question arises - who will implement this in the future? It is necessary to be aware of which scientific centers will be included there, and on what conditions. To exaggerate: IBH should after some time become almost a commercial organization, coming out of the bosom of academic science to organize around. Which of the research centers can become, and under what conditions? This issue does not yet have a solution, an organizational core around which management chains would develop. I think so.

Alexander ARSENYEV:

May I comment? At one time, IBH belonged to (and still belongs to) Academy of Sciences. But there was such an organization "Biogen", which was above him. And she started functioning normally. Another thing is that it did not have time to develop. It seems to me that superstructures are possible, which could include organizations of different departmental subordination.

Alexander GORDEEV:

What does "enter" mean?

Alexander ARSENYEV:

I do not know – somehow under the Soviet regime they entered.

Alexander GORDEEV:

Under Soviet rule, everything was according to plan – everyone was included in everything. It was generally a single organization.

Vadim GOVORUN:

Can I comment? I am not an expert in the pharmacological business, but I will still present the considerations of an "amateur from the outside". You see, when we talk about building Big Pharma, everyone present understands that in fact, from the point of view of the global big pharma, there is no market in Russia, i.e. the Russian market, from the point of view of three or four large pharmaceutical corporations, is very small. And there is a problem here. Any large pharmaceutical companies coming here already have large market segments around the world – it is profitable for them. This is, let's say, a kind of small "pie". The path that we are discussing today (as Valery Ivanovich said at the very beginning) should be this: some kind of national strategy for the development of the drug base should appear. What does the country need? What drugs can be attributed to drugs that, in any case, should be produced by Russian enterprises? Because it's biosecurity.

Without them, when oil runs out or prices plummet, people will start dying, because there will be nothing to really buy. The second stage is that the research teams that exist today, when they achieve decisive success in modeling in prediction, or when they group semi-finished products, they can be purchased by Big Pharma. This is not so bad, because not only the competitive culture of all the first stages is preserved, but also develops. And only then in the future, if we talk about it seriously, we can raise the question that domestic enterprises or a consortium or organizations that produce what is needed are present on the market with turnover, with money, with everything else, acquiring or interacting with research groups, and some developments They are beginning to expand both in Russia and abroad at the same time. To do this, you just need material resources. So any "big pharma" in one country, even as big as Russia, but not densely populated, is not very competitive.

There are simple things. Here we are talking about how to make IBH a central institute for the production of pharmaceuticals, combining it with that, the fifth, the tenth – and why? The markets for many drugs here are in fact only tens of millions of dollars. This is how the market structure works. And most of the drugs consumed in the Russian Federation today are far from original drugs. This should be borne in mind when discussing such serious issues with conclusions.

Of course, platforms within the technology of creating drugs should not only exist, they should be supported in every possible way. There will come a time when the business, which has developed in the conditions of the production of generics and those drugs that it is advisable for the state to purchase inside the country, will begin to seriously think about starting expansion. Because without expansion, this business will not be competitive. There are only 140 million of us, which is not much.

Alexander GORDEEV:

As far as I understand, it does not say that it is necessary to create an abstract "big pharma" at all. Here we are talking about the fact that if a drug strategy, a drug doctrine is adopted, then some systems of interaction between existing pharmaceutical enterprises should be prescribed there, if we accept this or that line and those scientific centers that are currently both organizationally and administratively broken. There is no such system for interaction yet.

We have two more performances in the same vein. And then we will continue our discussion. Kapreliants Arseniy Sumbatovich.

Arseniy KAPRELYANTS:

I am the head of the laboratory at the Institute of Biochemistry. Baha RAS. I would like to express a few thoughts that we had when working with antibacterial compounds and vaccines, in particular against tuberculosis.

This slide shows a fairly trivial scheme, which has already been discussed here, of how modern medicinal compounds are created. I would like to focus on the first one – choosing a target. This is a very important point in this whole case. He is the first, the most important. How to do this is quite a debatable thing. There are different approaches. You can do a total screening, you can use the so-called rational approach. That is, based on some ideas, on some of our knowledge, we can choose certain reductions that will later be used to develop antagonists or, conversely, activators of this target, etc. But there is a big limitation here, which is that our knowledge is the limits. In this sense, we can only apply what we know. And what we don't know remains outside the brackets. Nevertheless, screening, which is being carried out now in many places, remains an important element, since it is screening that can give us new targets, new knowledge, and then after the fact we can consider what it is.

In fact, there are several examples that suggest that this is exactly what happens. The discovery of the well–known Johnson & Johnson compound is a very promising, very good anti-tuberculosis, it was first discovered, and now it is starting to unwind how it acts on what mechanism, at what stage of metabolism it works. Everything is kind of topsy-turvy. That's one thing.

The second thing I would like to focus on. The existing paradigm is in silico, in vitro, in vivo. This is a generally accepted chain that works in many cases, but in many cases it does not work – and in quite important cases. For example, the well-known mechanisms of action as in tuberculosis. There is such an enzyme isocitrate lyase, a well-known Krebs cycle enzyme. This enzyme is very important for the life of microbes inside the cell inside the body for reproduction. This became clear, but before that, in vitro studies were conducted, which yielded nothing. It turned out to be an interesting situation when the inhibitors of this enzyme did not work in vitro, they work in vivo and this makes special sense, because in vivo the metabolism is rebuilt, etc. and therefore it becomes effective. I would like to say that this paradigm – in silico, in vitro, in vivo does not always work. An example from our laboratory is that we are dealing with certain secreted proteins, growth factors of mycobacteria, including Mycobacterium tuberculosis, which showed approximately the same behavior. Inactivating them, a complete knockout of these substances, these proteins does not lead to some kind of in vitro phenotype, you don't see anything, it's as if nothing happens to the bacteria, everything is fine. But in vivo there is a very large loss of virulence. This is very significant. It is so essential that on the basis of such mycobacteria we can create live vaccines that can be used. These are considerations about this whole synthesis and screening paradigm.

Here on the right it says which people and specialties should participate in each particular moment. Different specialties are involved here. Our experience of life leads to the idea that in order to implement all this, there are not enough intellectual means of any group, any laboratory, or even an institute. Maybe this is a rather trivial remark, nevertheless, in our practice it is very important. It seems to me that in order to create an anti-tuberculosis drug or a vaccine, the cooperation of all these people who exist here is necessary. It should be an informal cooperation, that is, it should be a community of people who are subordinated to one goal – specific, explicit, clearly formulated, vague. This should not be a study in the field, etc., it should be a study to create a specific anti-tuberculosis drug. We call such an education, if you like, a "scientific cluster". This education should not be static, but mobile, it should be possible that this education is created for a certain period of time for a given task, for a given project, but it exists and it is aimed at accepting some specific idea, some specific, in this case, a possible chemical compound.

This is an example of a newly formed cluster in the field of tuberculosis. We had such a meeting and the participants, who are shown below, organized themselves into a kind of tuberculosis cluster, but there are specialists there mainly who are associated with experimental tuberculosis. People who know how to cultivate bacteria, who know how to model systems, who know epidemiology well. This cluster does not include everything that is necessary to start working on the creation of a new drug.

Here is a consideration for discussion. Thanks for attention.

Alexander GORDEEV:

Thanks. And why informal associations? You create for a specific task, you want to solve a specific project. Why informal?

Arseniy KAPRELYANTS:

I'll tell you. It is virtually informal until it accepts some task. As soon as it is accepted, it becomes structured. But this does not mean that the entire consortium will work on this task.

Alexander GORDEEV:

Thanks. Klimov Nikolay Anatolyevich, please.

Nikolai KLIMOV:

I represent the organization "Biomedical Center". This is a non-governmental organization that was established in 1998, located on 400 sq.m of laboratory space. This is half of a standard kindergarten, which is rented, has a number of good devices and several well-equipped laboratories. For five years we have been working, in particular, within the framework of the interdepartmental scientific and technical program "New generation Vaccines", which, unfortunately, ended in 2005. A new program is being created, but it cannot be fully created. My report is illustrative, I prepared these pictures for a more scientific discussion, in a narrower circle, but my report perfectly illustrates the problems that we have just heard and discussed.

This is our hero – the AIDS virus. Our team discovered the first case of HIV infection in St. Petersburg back in 1987. We isolated the virus and our studies, which were confirmed by studies, in particular, at the Pokrovsky Center and other groups and our foreign colleagues, showed that the human immunodeficiency virus that circulates in our country is different from foreign viruses. It differs from subtype B virus, which circulates in the USA and in Western European countries. It differs even from the subtype A virus that circulates in Africa. Here's a question for you about Bigpharma. Will bigpharma, which is also developing HIV vaccines based on subtypes of type B, come here? Will it come to Russia? Of course, it won't come, because our virus is different from the Western one, and we will have to make the vaccine ourselves. Here is the data that suggests that subtype A is a red field that prevails, and also prevails A–B is a recombinant. Our team sequenced the complete genomes of the virus by the method of overlapping fragments. All this has been published many times. Based on the results obtained, we began to design a DNA vaccine against the human immunodeficiency virus. This is also a completely new word in pharmaceuticals, since a lot of work is devoted to gene therapy and gene vaccination, but so far the pharmaceutical industry does not produce such drugs. We selected four genes – a gene as a structural gene, reverse transcriptase, a gene that encodes a key replication enzyme, the gp160 envelope protein gene, and the nef regulatory gene. Using these four genes, we have created a DNA vaccine, which is a mixture of four plasmid DNA that enter the cells of the body and begin to synthesize viral proteins there. This is different from what was used before, because earlier, if you use vaccines based on a killed virus, vaccines based on individual viral proteins or other viral components, you induce mainly a humoral immune response, that is, the synthesis of antibodies. These constructions induce, on the contrary, cellular immunity, which is what we are fighting for. After we learned how to do this and seriously modified the genes, we dramatically increased the synthesis of these proteins. Our vaccine is a test tube or ampoule with a sterile solution of four plasmid DNA intended for intramuscular administration.

We have worked out the purification system, quality control... by the way, our Tarasevich Control Institute (ed. – L.A. Tarasevich State Research Institute for Standardization and Control of Medical Biological Preparations of the Ministry of Health of the Russian Federation) has not developed requirements for such substances. In America, the CDC (ed. – Centers for Disease Control and Prevention) and in Europe, such quality criteria have been developed and fixed in regulatory documents, unfortunately, we do not have this. We adhered to the requirements imposed by the CDC, in a number of parameters we are even cleaner than required, according to American regulatory documents. When our DNA vaccine was injected into mice, the induction of cellular immunity was registered, the parameters of which, somewhat simplified, are shown in this picture. That is, toxic lymphocytes are induced and CD8, CD4 are activated, and such an immune response lasts until the 12th week, and then nothing ... then there are immunological memory cells and it is they who must meet the virus when it enters the body, react and the resulting toxic lymphocytes must destroy the cells affected by the virus. All this works well on a mouse model, but no one knows whether it will work on a human, because there is no adequate model on laboratory animals. It is necessary to go through all three long phases of clinical trials, and the largest – the third – phase of clinical trials to find out whether this design works on a person or not. So, the first difficulty we have encountered is that the absolute novelty of such substances for the pharmaceutical industry, for healthcare, although a huge number of hopes are associated with the use of DNA for therapeutic and preventive purposes, in particular for hemophilia, for vaccination against viruses. But so far, these studies have not yet gone beyond laboratory tests.

And the second thing we are faced with is rather high doses of DNA. If we inject about 50 micrograms intramuscularly into a mouse (and our American colleagues, who are much richer than us, they work on monkeys and there for 3 milligrams), and we have 4 components, then we get 12 milligrams – this is a very large dose even for its manufacture, not only from the point of view of possible complications. Therefore, we are now working on the use of nanotechnology in order to reduce the immunizing dose by about two orders of magnitude, by forming nanoparticles that would contain our DNA. This contributes to its better penetration into the cells, its better preservation. These are nanoparticles based on the simplest polycationic molecules, they bind with a high intensity of DNA and thus we will be able to develop a new dosage form for human use.

In our experience, already touching on the topic of our meeting today, it seems to us that business ([whether it is] "big pharma", "small pharma" or "medium pharma")... still, there is no need to build illusions. Business needs specific development projects, at the end of which there is always one specific product for a specific market. Where a business plan begins, business comes there. The other happens only as an exception to the rule. But such tests, which it is unclear how they will end ... It's not enough that they themselves are not experimental ... Although, on the one hand, they are also experimental: we see that there should be a specific product at the output, but no one knows whether it will work. The risk is huge, business does not climb here. Even in the West, developments on subtype B, subtype D are carried out with the huge participation of state structures, with state funding, even "big pharma" does not take the risk of investing money in such developments, well, even more so here. Of course, the state must finance science, which means that business picks up on this at later stages of testing.

Alexander GORDEEV:

Thanks. Questions? Then our program was exhausted. If there are any speeches, someone wants some kind of remark…

Vladimir POROIKOV:

I have a question for Olga Anatolyevna. In fact, even two.

One question relates to the proposal to apply for funding for 2008. How, what is expected there? Does it correlate with the questionnaire currently being distributed in the field of "living systems", or does it not correlate in any way? The questionnaire is called "Problems and prospects of medical and pharmaceutical technologies". Are there any intersections in priorities?

And the second question relates to the development programs of scientific institutions. Another questionnaire is distributed for managers. It is not entirely clear what the development program is, what this money can go to, who can it be allocated to? Thanks.

Alexander GORDEEV:

It's easier here... about this questionnaire. This work, which is being carried out within the framework of the program jointly, the customers are the Ministry of Education and Science, Rosnauka. While this is not formulated as a document, it is rather a future development program. But since there are working groups within the framework of the priority area of "living systems" that determine certain priorities for financing, in principle, they, as representatives of this group and the expert community in general, are developing these technological platforms. To some extent, we can assume that this is the view of experts on what is interesting in this direction. But not some kind of official document on priorities. While.

And as for innovative institutions, this is…

Olga LESINA:

These programs, as I understand it, are to help working groups. If this year (I'll come back a little bit) we had so-called search research probes to understand what the groundwork is and how institutions live, and there were small amounts, then from this year, most likely, we will have one lot, one winner. This also applies to exploratory research. That's how to choose the right direction, you also need to know the situation, what is happening, and which critical technologies will have more weight. The questionnaire for this.

As for development programs, as far as I know, in the President's message it was a proposal to hold a competition for the development of research institutes by analogy with the competition of innovative universities. That year, 30 billion were allocated. The Ministry of Education and Science, we simply announced a competition and chose an organization that would help choose the tender documentation for these competitions. We also did this, and the MON is going to do such contests.

Alexander GORDEEV:

That's right, only there really is a resolution, there is a message from the president, so this is an indication that something similar should be done, as was done for the innovative development of universities. The whole program will start in 2009, most likely. In 2008, winners will indeed be selected, while it has not yet been definitively formulated what the institute's scientific development program is, because according to ideology, I want to lay down the development of applied components. At the same time, there are quite a lot of applied and quite a lot of players in the academic sector. And hence such questions.

What is the program? What kind of money do you still want, and this, apparently, will insist on it, that there should be extra-budgetary co-financing? What is extra-budgetary co-financing? And what result should the program have, confirming the success of this program, that is, what should be created as a result, what arguments should the organization have that what was created will really work [and not] be idle. Because updating the database by a billion is actually serious costs and serious changes in the structure of the institute itself, because the institute, sitting on estimated funding, simply will not be able to maintain all this equipment. As I understand it, these questions are still open.

The last such round table this year will be on November 21, here. Khlunova's department will conduct it, Lebedev is doing this there, and discussions are tied to this. So far, there is a feeling that the ideology of technological platforms, that is, the creation of platforms, a set of platforms as a result of the implementation of this program, may be some kind of argument for the sustainable functioning of a scientific organization in the future. But again there is a question, and there it is key, as with state institutions. There is still a nuance that if a state institution decides, in addition to service contracts, also purchase and sale contracts, so that they can bring these series to the market. While they can't do that, then they will also be able to participate more actively in this.

Olga LESINA:

I want to add: this year we have another new problem that the Federal Targeted Investment Program can be extended to FSUE. We are now trying to resolve this issue, that is, it is meant only for state institutions. How to get out of this is also a question. Therefore, these are rather problematic issues that we are looking for solutions to.

Alexander GORDEEV:

All in one. Some in one cannot receive, and others in the other.

Oleg KORZINOV:

I understand that non-governmental organizations will not participate in this program for the selection of innovative research institutes…

Olga LESINA:

They are still an open question. I mean only the FAIP, and we still have an open competition, there are no restrictions.

Alexander GORDEEV:

Here, on the contrary, from the point of view of the requirements that one wants to impose on the legislation, non-state and unitary ones can participate. The issue is with academic institutions, because they have serious problems proving their future break-even, let's say, and self-sufficiency, that is, the ability to commercialize what will be created. On the other hand, of course, there are trends that now (returning to copyrights) do not strongly favor the success of commercial organizations. But I think the situation will change there by 2009. So far, FSUE is in the lead.

Thank you very much. We will make recommendations of this round table at the exit, we will send them to you, post them on the website for comments. Thanks.

Published STRF.Ru 16.11.2007.

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21.12.2007