Genes, cells and biotechnologies: details
Today biology is not stamens–pistils, but physics
The topic of his lecture is "Genes, cells and biotechnologies".
How did you get into science?It was a long time ago.
I am a theoretical physicist by education. Graduated from the Moscow Institute of Physics and Technology, Faculty of Theoretical and Experimental Physics. I have always been interested in biology, but I realized that doing biology the way it was mostly done in the past, getting either a biological or medical education, is not very right now. Following the well-known saying that a physicist can always study biology, but a biologist is unlikely to study physics already, I decided to start with the basics, that is, learn physics, and then go to biology. In fact, this was dictated, first of all, by the fact that today biology is not stamens-pistils, but physics. Including mathematics and computer science.
Indeed, today, from the point of view of the tools that are used for research, a person needs to know physics and physical principles well. Because these principles are actively used today as a tool. A fundamentally different era of semiconductors and nanomaterials was coming. What physics has done, which has come to biology today, for example, in the form of sequencing (NGS, next-generation sequencing, sequencing of genomes of a new generation). It came in the form of new microscopes, for which Nobel prizes are awarded, new principles for studying living matter.
How did your scientific work begin?I started with working with plants, with genetic engineering of plants.
At that time, Monsanto was interested in our research, because we were one of the first in the world who wanted to obtain transgenic plants. But this interaction did not work out then. Monsanto had an interest, and the Glavmicrobioprom, to which we belonged, was a paramilitary organization, since all industrial biotechnology and microbiology was a "dual-use technology". In peacetime, various amino acids and additives were produced, but within 24 hours the entire production had to be rebuilt to produce some kind of plague, anthrax, in order to flood the whole world with all this. But that was a long time ago.
Then other times actually came, and I had to do various things. Then I moved from plants, let's say, to a higher level, if you look at the tree of evolutionary development: I took up insects (studied certain things on the fly of a fruit fly). Then, gradually evolving in my work, I grew up to study oncology, studying the problem of cancer and antitumor immunotherapy. I have been doing these things successfully since 1995. As a result, we began, in particular, to work together with the Kashirka Cancer Center. By the way, they worked under the program of the Moscow government, it was funded by Yuri Mikhailovich Luzhkov. And it has been funded for a long time. We seem to have received the last finances in 2011 or 2012. And it began approximately in 1995.
This program included a lot of organizations. Moreover, organizations are not only from Moscow. Organizations from Novosibirsk also worked. I mean in biology. There were also non-biological directions, there was even more spectrum. But they were all united, let's say, by the Moscow will and all this was supported by Moscow finances. And it developed very successfully. A lot has been done in different directions. And we have developed several types of vaccines. They partially passed, true, but, nevertheless, they passed clinical trials – they passed in St. Petersburg, tests in Moscow at several institutes. And, in general, we have developed a couple of antitumor vaccines that are still being used. But they turn out to be very expensive, because they are not included in the list of paid things, that is, they are not always allowed to everyone.
But the technology was developed, for which in 2004 a team of authors, including me, was awarded the prize of the Government of the Russian Federation for the development of new methods of cancer biotherapy. There were scientists and doctors from the Institute of Oncology named after him. Petrov is from St. Petersburg, from the Moscow Cancer Center on Kashirka, from the Herzen Research Institute, from somewhere else, I don't remember anymore. The team was 10 people. It was interesting to work effectively combining both biological and other methods.
At what stage did you study the behavior of stem cells?When I was working in various areas related to oncology (back in the mid-90s), we had the idea that no matter how we try to destroy a tumor, it always arises from somewhere.
It arises from somewhere, it lives inside the body. Actually, then there were some parallels with the fact that there may be a tumor stem cell, which gives rise to the tumor itself. It is the elimination of the tumor stem cell that can lead to the destruction of the tumor. Well, this led to the fact that they became interested in stem cells in general and switched to human stem cells. And not those stem cells that everyone studies, adult stem cells that are interesting in themselves, but they have fewer possibilities, but the so-called embryonic human stem cells that have unlimited possibilities, which in scientific language is called pluripotency. After the first publication of the Japanese Shinya Yamanaki on reprogramming an adult organism to a pluripotent state appeared in 2006, we, a little later, engaged in reprogramming cells and obtaining induced pluripotent stem cells. Shinya Yamanaka, as the author of this direction, received the Nobel Prize for this in 2012.
These are interesting things that say today that biology is changing the basics somewhat. There was a hypothesis that in fact, probably, there are no certain cell types. Previously, it was believed that there are cellular types, and they are fixed. It turns out that, most likely, these are cellular states, and even in an adult organism, a cell can be transferred from one state to another. And the tumor transformation itself is one of the most striking manifestations of this process when it takes place naturally. Another thing is that it passes naturally, it is poorly controlled, so tumor cells are obtained. If it passes under control, then the cell can switch to another state under controlled conditions and become a pluripotent cell, a nerve cell, an intestinal cell. Now a lot of studies are being conducted in this direction, which have demonstrated this change in the state of an adult cell, when a skin cell can become, for example, a heart cell.
In recent years, I have been working in the field of studying and applying reprogramming technology, studying various human diseases with the help of this technology – mainly those that are incurable today. And also using these technologies to study the fundamental foundations of cell functioning, that is, the acquisition by a cell of a particular specialization, the preservation by this cell of specialization and the possibilities of changing specialization – in order to understand why the cell acquires specialization, according to what laws. Understanding these laws, somehow designing them, it is possible to change the fate of a cell, to make a cell an arc of specialization from one cell, which will be necessary for practical purposes in the future. That's about the ideology of the development of scientific research.
How is the interaction of fundamental science and commerce built?Along the way, of course, there were some practical things.
As I have already said, this is also an antitumor vaccine that we have implemented and for which we received a government award. Since the antitumor vaccine implied the use of cells and genes with which we change these cells, we were actually the first to use the so-called gene therapy in clinical trials in Russia. Thanks to the study of the problems of gene therapy and the study of gene therapy on models, a special direction was subsequently identified in the laboratory: how to stimulate the formation of blood vessels in the body with the help of genes. There is a whole group of genes involved in the formation of blood vessels.
This is quite an interesting thing. In principle, blood vessels are not normally formed in an adult body. Only with some damage, and so the person has developed – and that's it. But sometimes, for therapeutic purposes, it is necessary that the formation of blood vessels takes place. For example, ischemic conditions, when blood vessels die. Following the blood vessels, tissues that are deprived of nutrition (both the necessary substances and oxygen) and the removal of waste products also die.
The idea was this: what if by delivering additional portions of genes that control the growth of blood vessels to these types of tissues, we can stimulate the growth of blood vessels and thereby restore blood supply? Pilot experiments were conducted with the Bakulevsky Institute, this is the beginning of the 2000s. But, unfortunately, then it was possible to conduct only pilot studies, the drug could not be brought to the final stage. Only after a long period of time, together with a commercial company, the Human Stem Cell Institute, we completed clinical trials of a gene therapy drug, which was named "Neovasculgen". And since 2012, Neovasculgen has received a registration certificate in Russia and is actually now available for sale. He was also recently registered in Ukraine and is being registered in the USA.
This is the third gene therapy drug in the world. Before that, two more drugs were released in China a couple of years ago. "Neovasculgen" is the first in its class, that is, aimed at the treatment of lower limb ischemia. Therefore, it is, of course, quite unique, the original development was. We are trying, as far as possible, to translate our research into such a practical plane. My role in commercialization is absolutely not great, I don't want to do it. It's none of my business. Scientists should be engaged in science. As soon as they start doing business, they become merchants. These are no longer scientists. Then it is necessary to remove them from the organization. In general, science, as you know, is funded only by the state. Because only the state can afford such long-term deposits. No commercial firm, no commercial structures are interested in financing science. They are interested in financing a commercial product. This is not the same at all.
Do you somehow distinguish the Moscow scientific environment for yourself, or do you, in principle, not perceive science geographically?The results of scientific work, of course, are not perceived in some geographical context.
But the organization cannot but be perceived without separation from some structure, infrastructure. From some base. There will never be a result without organization. Today there is no organization of science, so there can be no result. Actually, as in the state: the state disappeared in the 1990s, everything turned into chaos, then science turned into chaos, which, as you know, physically and materially left Russia and moved to other countries. Because it was organized there. It was clear there what to do in order to do this business. To do science is to do business. Business is business. This is not selling pies on the street, although this is also a big deal, but still science is also a business.
Another thing is that there may not even be buyers for today's scientific products. And most often today it does not happen. The purchase of a scientific product has been postponed. That is, it should be a long investment in scientific production. This is the organization of the scientific process. To be honest, Yuri Mikhailovich Luzhkov understood this very well. Along with the fact that he always demanded at the end the translation of the scientific result into some practical plane, he clearly understood that there could be no practical result if long-term investments did not come to science. After all, what is a practical result? In fact, as a result of the scientific process, scientific research, we discover some laws of nature, how this nature is arranged, according to what principle it functions. We open some small cog of the universe. And what is practical use? The practical use of this cog is when an engineer has to create an entire machine based on this cog. To create something that does not exist in nature. Here is a practical use. This is engineering. This is a completely different category of people.
The engineering part has been completely destroyed over the past 20 years. Therefore, even if there are some scientific developments, they will not be in demand in Russia for a long time, because there is no one to work with the results of scientific activity. There is no category of people who can be called engineers. So, Yuri Mikhailovich's program, which was conducted in Moscow, was very well balanced. There was a kind of organizing beginning. This is one time. It is clear that the organizing principle must rest on some kind of foundation that creates a material basis. That was also the case. It was clear that there should be a practical result in the end, but it should not be a shapkozakidatelstvo. That is, we should not quickly open five new laws of nature before the new year, starting today, and make 5 types of electric kettles based on these laws of nature. That is, there was a clear and clear understanding that these were investments that would bear fruit, but not this year.
Here is the case of the commercialization of a gene therapy drug in the future – this is a good example. The idea of this gene therapy drug, "Neovasculgen", originated in the late 90s. Some first research and studies were conducted. The program had already ended when this drug was commercialized by completely different people, those who had enough time and money to commercialize it. The origin was in one infrastructure environment, and commercialization took place in another. There is nothing so surprising here, since each infrastructure environment must ensure the cultivation of its own product, let's call it a product for its specific level. Quite a large number of people worked in the Moscow program. From Novosibirsk, from St. Petersburg, from Moscow, of course. Only in the biological section of the program, where I have been co-director for the past few years, there were about two dozen organizations.
That is, all this work was carried out under the auspices of the Luzhkov program.Yes, that's right.
Under the aegis, under the ideology. The program was dedicated to oncology. Of course, when big tasks are set, only complex approaches to solving are possible. Accordingly, those people whose participation was necessary, who were carriers of certain knowledge, certain ideas and directions, were involved in the program in order to realize the main idea. It's just like an atomic or space project. The person who was needed to complete this project became a part of this project.
Therefore, the idea that is now popular, that you need to build on impact factors and journals in order to successfully reach some advanced positions, is complete nonsense. People have gone crazy: now there should be only impact factors and citation indexes. Yes, no one needs these citation indexes. Absolutely meaningless and unnecessary thing. Because, after all, we all know that we have to fly into space, make an atomic bomb, launch a power plant. There should be completely different things on the way out. And impact factors and citations are a kind of virtual assessment. If a person is very rich, then he can be evaluated this way. If you are not very rich, then you need to proceed from project financing, set good tasks, interesting, large practical tasks and try to solve them. Because then, if a good practical goal is set, which has not yet been solved in the world (and not here in Uryupinsk, or on Gubkin Street, where I am sitting), then there will be very high achievements in science, without which new technologies, the solution of fundamental tasks cannot be achieved. And after that there will already be some citations and impact factors. Which, in fact, are not really needed anyway. Take Peter Higgs, he has publications with almost no citations, in the late 60s he proposed the idea of his boson, in 2012 the Higgs boson was confirmed experimentally, and in 2013 P. Higgs was awarded the Nobel Prize. And to prove the existence of this boson, scientists from many countries have united, their governments have allocated money for the construction of a large hadron collider, here is an example of such a project.
Portal "Eternal youth" http://vechnayamolodost.ru28.11.2014