by Academician Anatoly MIROSHNIKOV, Chairman of the Pushchino Scientific Center of the Russian Academy of Sciences

On the right bank of the Oka river about one hundred kilometers to the south of Moscow, there is a young town of Pushchino. Its population isn't big - around 20000 people. However, it is well-known not only in our country, but also beyond its borders. In 2005, it was given the status of a "town of science" by the RF government resolution. This means acknowledgment of a high level of fundamental studies and applied works, carried out in the institutes of the Pushchino Scientific Center of the Russian Academy of Sciences. This year it marked its 50th birth anniversary.

The following circumstances preceded its creation. In the middle of the 20th century, the level of knowledge about the mechanisms of a living cell operation significantly fell behind the present one. However, it was then that new science - molecular biology - was created. A variety of revolutionary works, including a model of spatial pattern of a DNA molecule proposed by American biochemist James Watson and English biophysicist and geneticist Francis Crik (Nobel laureates of 1962) in 1953, promoted its rapid development. Three years later postgraduate student of Moscow State University named after Lomonosov, Alexander Spirin (Academician since 1970) and his supervisor of studies Professor Andrey Belozersky* (Academician since 1962) predicted existence of information RNA.

At that time the general level of national biology remained behind the world level due to long-term domination of the dogmatic views of Academician Trofim Lysenko and his supporters in our country. The existing network of institutes and their material base didn't conform to the current requirements. Studies of protein and nucleic acids, molecular organization and self-regulation of the cell, its energetics, problems of general virology, biochemistry of microorganisms, photosynthesis lagged behind progressive foreign researches. Therefore, on the initiative of the USSR Academy of Sciences President Academician Alexander Nesmeyanov (1899 - 1980), there was raised an issue to form a major center of biological studies equipped with the up-to-date equipment and facilities.

In April 1956, the government made a decision to build a scientific town in the Moscow Region consisting of

* See: B. Vanyushin, "At the Source of Molecular Biology", Science in Russia, No. 5, 2005. - Ed.

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eight institutes: Biological Physics, Microbiology, Biological Chemistry of Animals, Plant Physiology, Heteroorganic Compounds, Chemistry of Rare Elements, Chemistry of Natural Compounds and Aerophysics. At that time the Academy of Sciences was allotted a plot of land of 761,8 ha in the village of Pushchino of Serpukhov district for these purposes and the radio-astronomy station of Physical Institute named after P. Lebedev (FIAN). In May 1959, the first observations were carried out with a 22-meter radio telescope. Other planned objects appeared significantly later: the large-scale costs relating to the creation of the USSR Academy of Sciences Siberian Branch in 1957 compelled one to change the original target dates. However, at the beginning of the 1960s the construction of the town near Moscow was speeded up.

On March 3, 1961, the foundation stone of the Institute of Biological Physics (founded in 1952 by Alexander Kuzin, the USSR Academy of Sciences corresponding member) was laid, and two years later the USSR Academy of Sciences Scientific Center of Biological Studies (SCBS) was formed in Pushchino. The outstanding Soviet biophysicist, the USSR Academy of Sciences corresponding member (Academician since 1966) Gleb Frank (1904 - 1976) headed it. Alexander Cherkashin became the first deputy Director on whose shoulders rested the main pains relating to the creation of Akademgorodok.

The great role in establishing the Center belongs to Frank. To solve the objectives of modern molecular biology, it became possible to coordinate the studies of biophysicists, biochemists, physiologists, cytologists, mathematicians, microbiologists in Pushchino by the efforts of this outstanding scientist and talented organizer.

Well-known microbiologist, biochemist, the USSR Academy of Sciences corresponding member (Academician since 1979) Georgy Skryabin (1917 - 1989), who replaced him at this post in 1967, and the USSR Academy of Sciences young corresponding member Genrikh Ivanitsky, who headed the Center in 1976, continued Frank's initiatives. The problems of colleagues from Pushchino came into the view of the USSR Academy of Sciences presidents, Academicians Mstislav Keldysh (1961 - 1975), Anatoly Alexandrov* (1975 - 1986), vice-presidents Andrey Belozersky (1971 - 1972), Yuri Ovchinnikov (1974 - 1988), and Academicians Alexander Bayev**, Mikhail Shemyakin and others. Thus, under the direction and with participation of Yuri Ovchinnikov there were prepared three government resolutions to develop domestic physicochemical biology, which stimulated development of Pushchino Scientific Center and allowed to sharply raise the level and rates of works in this area.

At the end of the 1960s-1970s, the Center was formed as a complex of modern institutes of biological profile, which became well-known in our country and abroad during a short period of time. Researches in the field of biophysics, microbiology and biochemistry were performed in these institutes; a number of aspects relating to plant physiology and photosynthesis, soil science were sought for. The results were applied in medicine, agriculture, industry, which was marked by a number of high state awards. The young town with wide straight streets, modern residential houses, schools, kindergartens, recreation areas grew together with the scientific institutions.

In 1990, the USSR Academy of Sciences SCBS was modified into Pushchino Scientific Center (PSC). It was governed by the presidium. The outstanding scientist in

* See: N. Ponomarev-Stepnoi, "At the Head of the Nuclear Branch", Science in Russia, No. 2, 2003. - Ed.

** See: A. Bayev, "A Glimpse into the 21st Century Biology", Science in Russia, No. 4, 1994. - Ed.

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the area of physicochemical biology, one of the founders of modern molecular biology, a member the USSR Academy of Sciences Presidium, Academician Alexander Spirin was appointed its chairman. Owing to tireless scientific and organizational activity, he managed, to a considerable degree, preserve a high level of research and scientific potential of the Center in the 1990s, which didn't prove to be simple.

One has to admit: perestroika and consequent economic reforms affected the life of the institutes, and, as a result, the whole town of Pushchino. Many works were scaled down, "brain drain" was in progress. We have only to regret: from 1987 to 2002 the Center lost almost 500 employees, mainly, young, perspective people. Naturally, they found an application for their knowledge and skill. But in foreign universities and laboratories not in Russia.

In 1999, Academician Vladimir Shuvalov, well-known for his studies of photosynthesis, became chairman of the presidium of the USSR Academy of Sciences PSC. In 2006, Academician Anatoly Miroshnikov, whose scientific interests are concentrated on the field of physicochemical biology, replaced him.

Presently, PSC unites nine institutes of biological profile and Radio-Astronomical Observatory of the FIAN astrocosmic Center. Today more than 3000 people work here, among them 1200 research scientists. About 800 scientists have a degree of a Doctor or Candidate of Sciences in the field of biology, medicine, chemistry, physics, mathematics. What problems do they solve, what do they work at?

The Institute of Biochemistry and Physiology of Microorganisms (IBPM) named after G. Skryabin, founded in 1965, is one of the leading ones in the country in the field of microbiology and biotechnology. Academician Nikolai Ierusalimsky was its first director till 1967, then Academician Georgi Skryabin, and since 1989-the RAS corresponding member Alexander Boronin. Here they study the variety of the microbial world and principles of its interaction with the environment. The All-Russia Collection of the cultures of microorganisms created and preserved within its walls is the largest in our country and has an international status. In its basic funds there are 14000 and in working collections - 3000 strains of actinomycetes, yeast and filament fungi, and genetically modified structures.

Of late, new species of actinobacteria have been discovered. A possibility of using some biological polymers as a taxonomic marker was demonstrated for the first time. There were found new cell structures of microorganisms, including specific complex organized channels in the cellular wall of yeast playing an important role in their adaptation to environmental conditions. The presence of viable forms of yeast in permafrost of Siberia, which had been in an anabiotic form there for 3 - 5 mln years, was authentically stated for the first time. These data reveal the opportunities, which were unknown earlier, to solve the problems of evolution, allow to evaluate the hypothesis on panspermia in a new fashion (spreading of life in the Universe from one cosmic body to others) in favor of the idea of simultaneous transfer of eukaryotes and procaryotes, which is in agreement with the conclusions of molecular genetics on approximately similar antiquity of the three kingdoms of living organisms: eubacteria, eukaryotes, archaeota*.

Also, IBPM employees study the issues of spread, classification and evolution of bacterial plasmids - a heredity factor - located in cells outside chromosomes. There is formed a collection of destroyer strains of petroleum products; preconditions are created for purposeful construction of microbial associations with specific features for efficient biotechnologies of environmental cleaning from anthropogenic pollutants.

The Institute played an important role in the organization of microbiological industry as an independent branch in our country, as the development of the scientif-

* See: L. Vorobyova, "This Wonderworld of Archaeota", Science in Russia, No. 5, 2004. - Ed.

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ic principles for obtain single cell protein in the first large project successfully implemented there. The application of the methods of gene engineering of microorganisms became an important step. It was in the IBPM that the first domestic strains of superproducers of some ferments had been thus obtained.

The Institute scientists developed the scientific basis of ecologically safe detoxification of dangerous toxic substances-mustard gas and lewisite, large-scale technologies of obtaining citric acid, methods of production of prednisolone, hydrocortisone and other medical preparations.

The majority of scientific and applied studies are carried out here by using an experimental-technological fermentation plant, which together with the All-Russia Collection of microorganisms is included in the "List of unique research and experimental plants of national importance".

The Institute of Photosynthesis founded in 1966 (its first director was Vyacheslav Yevstigneyev, Doctor of Biological Sciences) and the Institute of Fundamental Problems of Biology, which became its successor, are continuers of the research schools of academicians Alexander Terenin, Alexander Krasnovsky Yelena Kondratyeva, the USSR Academy of Sciences corresponding member Anatoly Nichiporovich. Today, the Institute is headed by Academician Vladimir Shuvalov. Here they study molecular mechanisms of biological processes of energy transformation (mainly, in the process of photosynthesis of plants), structure and functions of membranes, formation of functionally active proteins, problems of photobiotechnology, stability and adaptation of ecosystems to external impacts.

Among its achievements one can single out elucidation of the sequence and determination of temporal characteristics of primary processes of light energy transforma-

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tion in the process of photosynthesis. Namely, it was discovered that primary acceptors (receivers) of electrons in photosynthetic reaction centers are pigments of chlorophyllous nature. On a par with this is a study of mechanism of water photooxydation and oxygen isolation in the similar process, and hydrogen metabolism and nitrogen fixation of photosynthetic microorganisms. The basics of photobiotechnological methods of obtaining hydrogen, ammonia, a number of enzymes and physiologically active compounds have been developed. Structural peculiarities of lipopolysaccharides (biopolymers, which are components of membranes) are discovered from photosynthetic bacteria defining their protective effect from lethal doses of endotoxins. A model of ecosystem operation is developed allowing to forecast its reactions to external impacts.

Organizer and the first director of the Institute of Protein in 1967 became Academician Alexander Spirin. Presently, the Institute is headed by Academician Lev Ovchinnikov. One of the main directions of its activity is a study of molecular mechanisms of protein biosynthesis, including control of this process at a transmission level, the basics of operation of ribosomes and their components. The second direction is a study of protein structure, including the three-dimensional pattern, and protein complexes with DNA.

The systems of preparative extra-cellular synthesis of protein and DNA developed at the Institute and the method of cultivating DNA and RNA colonies in the layer of polyacrylamide gel, allowing to clone genes outside the cell and find single molecules of nucleic acids are of innovative importance. The latter method creates preconditions for revolutionary improvement of cloning methods and diagnostics of viral infections and cancerous diseases. The systems of cell-free biosynthesis of protein hav been patented in Russia and abroad, produced by the

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Hoffman-La Roche Company (Switzerland) and widely used in laboratories and production in the world.

Soil science is among the basic fundamental biological disciplines. As an outstanding Russian natural scientist Vassily Dokuchayev (1846 - 1903) emphasized, "they are the very basis connecting the whole of biosphere into a single whole". In 1970, the Institute of Agricultural Chemistry and Soil Science (its organizer and first director was the USSR Academy of Sciences corresponding member Viktor Kovda) was created in the system of the USSR Academy of Sciences. After a number of changes in 1999, it became an independent Institute of Physicochemical and Biological Problems of Soil Science (it is headed by Valery Kudeyarov, Doctor of Biological Sciences). Here they study the mechanisms of processes of soil formation, transformation and operation of chemical substances under the natural and anthropogenically modified conditions. The connection of presence of magnetic minerals with bioclimatic conditions of soil formation in the Russian plain was demonstrated. The contents of bio-genetic magnetite can be used as a "record" about the former conditions of the environment. The obtained instrument allows to get quantitative characteristics of the climate, which existed hundreds of thousands years ago.

A new interdisciplinary scientific direction - "archeological soil science"* - is being developed at the Institute: by ancient soils preserved under kurgans (burial monuments), scientists reconstruct the conditions of natural environment of the past epochs. Such studies are extremely important for long-term forecasting of environmental changes.

Thus, the balance of hydrocarbon in the territory of Russia was estimated. Its topsoil (1/8th of the planet) is a long-term reservoir of this element (1/5th of the reserves in the world's soils). Contribution of breathing of the country's soils with regard to total emission of carbonic acid of this type is only 1/17th. In the emission component of the carbon circulation in our country, more than 80 percent of total emission of carbon dioxide is contributed by soil respiration. While industrial emission of CO₂ (burning down of fossil fuel, production of different goods, etc.) is estimated at less than 15 percent. Carbonic acid gas flow at the expense of the products of photosynthesis exceeds all types of CO₂ sources almost by 1 bln tons, which allows to consider Russia's territory as an ecological donor across the globe.

In 1979, a branch of the Institute of Bio-organic Chemistry named after M. Shemyakin was set up in Pushchino. Founder and first director of this branch was Academician Yuri Ovchinnikov. In 1987 - 1989, a modern biotechnological complex allowing to introduce the results of fundamental and applied studies into medical practice was set up here. Biologically active macromolecules-potential medical preparations-are sought for, screening of activity of a wide range of substances of both natural origin and synthetic by using cell-free cultures of cells and tissues, as well as laboratory animals-biological models of different pathologies and diseases of man-is under way. New perspective medicines are undergoing preclinical tests in accordance with GLP international standard. The latter requires use in toxicological studies of animals, free of pathogenic flora. The problem of their breeding was solved for the first time in our country in Pushchino.

At the same time so-called "eatable" vaccines are being created here-transgenic plants, namely, potato, expressing the gene of surface antigen of hepatitis В virus. Output of substances of medicines based on gene engineering proteins of man (lymphokines, peptide hormones, blood factors) is prepared. A factory, where human gene engineering insulin (insuran) will be produced among other preparations, is being designed.

In 1990, the Institute of Biophysics was reorganized by creating on its basis the Institute of Biophysics of the Cell and Institute of Theoretical and Experimental Biophysics. The first one is headed by the RAS corresponding member Yevgeni Fesenko. Here they study the mechanisms of reception, intracellular signalling, regulation, and influence of the factors of physical and chemical nature. Other directions are mechanisms of action of electromagnetic and acoustic fields, and ionizing radiation on cells and cellular systems, studies of the structure and functional features of biomolecules. Also, scientists are engaged in medical aspects of the cell biology. The main objects of their search are receptor cells of sensor systems, immunocompetent, nervous, and embryonic stem cells. As to the latter ones, the scientists have managed to find three conditions when they are differentiated into cardiac myocytes (cardiac muscle cells) with emergence of centers of spontaneous cardiac activity.

Cryobank of rare and dangerous species of plants and animals is created and replenished at the Institute. A new method of spectroscopy of biomolecules and cells is proposed based on infrared emission registration induced by light. Together with the RAS Institute of Mathematical Problems of Biology a digital system was developed, which is installed as an attachment on standard X-ray equipment and allows to get diagnostic pictures within 1 - 2 s without using a relevant film.

Presently, the Institute of Theoretical and Experimental Biophysics is headed by the Russian Academy of Sciences corresponding member Genrikh Ivanitsky. Here they carry out fundamental studies of physical and chemical mechanisms of operation of biological systems of different hierarchic levels and influence of environmental factors on them. Thus, for example, there were revealed and studied new self-oscillating and self-wave processes in the work of heart, brain, populations of microorganisms, in the suspensions of intracellular organelles.

Practical developments of the Institute employees concern, first of all, the needs of public health and biotech-

* See: V. Dyomkin et al., "What Old Mounds Tell Us", Science in Russia, No. 1, 2005. - Ed.

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nology. Here there are some results which are already used and have prospects of practical use in the near future. There was created technology for large-scale production of diagnostic biological microchips and control and program systems to process the results of analyses. Based on the methods of matrix thermovision of high resolution, there was proposed a system of noninvasive diagnostics and control over treatment efficiency of the illness of vessels and early detection of mastoncus. New inhibitors of multiple drug resistance of tumor cells, which aren't toxic for organism were discovered. A new generation of X-ray equipment of super high resolution (up to 10 µm) with minimization of radiation exposure on the object is developed. New methods of diagnostics, preventive measures and treatment are tested in the leading clinics of Moscow, St. Petersburg and near Moscow.

The idea of wide use of mathematical methods in biology was implemented in the USSR Academy of Sciences Research Computation Center. Albert Molchanov, Dr. Sc. (Phys. & Math.), headed it during 25 years. In 1992, the center was changed into the Russian Academy of Sciences Institute of Mathematical Problems. Presently, Viktor Lakhno, Dr. Sc. (Phys. & Math.), is at the head of it.

The Institute employees managed, for the first time, to decipher by the method of X-ray analysis the three-dimensional pattern of low density lipoprotein - a conjugated protein and lipidic complex containing more than 300000 atoms

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and involved in the atherosclerosis process. This research was carried out in cooperation with Freiburg Medical University (Germany), Nancy University, Strasbourg Institute of Genetics and Molecular and Cellular Biology (France). The works relating to creation and use of the methods of nonlinear physics and quantum mechanics in the problems of mathematical modelling of macro-molecular systems are fruitful. The theory of charge transfer to DNA explaining a wide set of experimental data has been devised. It is for the first time theoretically demonstrated that an ultralong transfer of charge at a distance of dozens of thousands of nucleotide pairs is possible in regular polynucleotide chains. This opens up prospects of using "DNA-conductors" in nano-electronics.

The concept is developed and information-computer main body of a generalized mathematical model of eukaryote cell is created. The main idea is in integration of private knowledge from different areas of biology, physics, chemistry and mathematics to describe the existing and create new models of a living cell operation. The resource under formation provides with the opportunities of making calculations of intracellular processes with a 32-processor cluster forming part of the Russian and global computer scientific networks.

It is impossible to imagine a modern natural scientist without high-accuracy and high-sensitivity instrumentation. In 1965, in Pushchino Special Design Bureau of biological instrument-making of the USSR Academy of

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Sciences was created; in 1994, it was changed into the RAS Institute of Biological Instrument-Making. Presently, Yevgeni Permyakov, Dr. Sc. (Biol.), heads it. Here instruments and equipment of more than 200 names are developed. 450 certificates of authorship and 40 patents in the USA, Germany, France, Great Britain, Japan confirm a high level and novelty of this equipment. Time and again it won medals of international fairs, and the designers - State Prizes in the field of science and technology.

One of the most important directions is devices to research thermodynamic features of biological systems: differential scanning and titration microcaloremeters. Also, spectral and optical equipment is designed, including spectrofluorimeters and spectrophotometers of wide profile. The equipment for cellular researches is constantly improved, including micromanipulators, equipment for cellular microsurgery. A principally new device to cultivate microorganisms is created. It allows to record and periodically reproduce stages of their growth by the program given by computer. Equipment is developed to extract highly purified powerful antioxidant - dihydromeletin - from industrial wood residue. It's widely used to can food and industrial oils, and in a number of food additives to strengthen vessels.

Speaking about the Center scientific divisions, one can't help mentioning Pushchino radio-astronomic observatory. In 1946, at the request of Academician Nikolai Papaleksi being in charge of FIAN laboratory, Vitaly Ginzburg, who was a young theorist then (future Nobel laureate) calculated solar noise and its crown within a meter range of waves and came to the conclusion that radio diameter of the Sun had to be significantly larger than an optical one. Observations confirmed this-even in a full phase of solar eclipse a registered flow of emission reduced only by half. Elated by the result, radio-physicists got down to create the first domestic radio-telescopes most of which were installed in the Crimea then.

By the middle of the 1950s new projects emerged. To implement them, a site on the bank of Oka river was chosen, the very place where the USSR Academy of Sciences management planned to build an academgorodok for institutes of biological profile. At the beginning of the 1960s researches of RF radiation of the Sun, Moon, primary planets, galactic gas nebulosity were actively carried out with a 22-meter radio telescope, catalogs of radio-sources in centimeter range of waves were drawn up. However, at that time up to present the basics of scientific programs were spectral researches of galactic radiation.

A little bit later construction of radio telescope DKR-1000 (its two beds have a form of paraboloid of 1000 m long and "opening" of 40 m wide) started in Pushchino. It gives an opportunity of making observations at wave length of 2.5 - 10 m. The device advantages were opened to the full when researching pulsar (neutron stars).

By May 1974, construction of the largest in Pushchino observatory and the most high sensitive instrument (dimensions 187 x 374 m) of a meter range in the world was completed. Its construction as of DKR-100 was started on the initiative of the founder and first manager of the observatory Viktor Vitkevich. For more than 30 years observations of pulsars and interplanetary plasma have been carried out with BSA radio telescope. Here they study clusters of galaxies, structure of compact radio sources by observing their blinking on dissimilarities of interplanetary plasma, parameters of interstellar medium.

Since 1988 the observatory has been headed by Rustam Dagkessamansky, Dr. Sc. (Phys. & Math.). In 1990, its collective joined in with the department of radio astronomy which was transferred to FIAN from the Russian Academy of Sciences Institute of Space Research, and there was set up Astrocosmic Center - one of FIAN departments. This resulted in enrichment of subjects of works in Pushchino, namely, involvement in implementation of "Radioastron" project. It supposes placement of automatic observatory into the Earth's orbit to watch distant extragalactic objects.

By commemorating the jubilee of the Scientific Center, recollecting the history of its establishing, giving credit for the results achieved during these years, it is natural to ask a question about future considerations for the nearest years. Our country holds leading positions by a number of directions of fundamental and applied bio-technological researches. Thus, now domestic scientific base in this area amounts to 12 percent of a relevant world sector (to compare: a share of Russia's economy doesn't exceed 2 percent). The market of bio-technologies is capable to ensure rates of growth exceeding average rates of growth of economy by several times. One can raise competitiveness of agriculture, many sectors of industry-chemical and petrochemical, light, food, ore-dressing and others with its help. PSC uniting one-third of the Russian scientific biological potential must become a center of crystallization of not only studies, but productions of bio-technological direction.

Based on the Center institutes, one has to organize personnel training in the area of physical and chemical biology capable, apart from purely scientific problems, to solve the problems of forming modern high-technology productions. Two institutions of higher learning are operating now in Pushchino: a branch of Lomonosov Moscow State University aimed, mainly, at preparing studies in the area of molecular biology, and Pushchino State University, carrying out training in the magistracy and graduate work in a number of directions of physical and chemical biology.