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by Nikolai KRASNIKOV, Head of Koltsovo Municipal Unit, Novosibirsk Region
The town of Koltsovo is located only 12 km away from the major Siberian center of Novosibirsk.
It has more than 10 thousand residents, a well-developed infrastructure and is bristling with enterprises (more than 160) of various kinds, both state and privately owned.
The history of Koltsovo begins in 1974, when the Soviet Government passed a special decree on the establishment of an All-Union Research Institute of Molecular Biology with the appropriate support facilities. The main objective of the new Center were studies of structural peculiarities and functions of the causal agents, or pathogenes, of some of the most dangerous infections, including their pathogenesis and the gathering of data on the variability of viruses together with the development of the appropriate therapeutic and preventive drugs and diagnostic preparations.
The steadily growing range of activities of the Center prompted its reorganization in 1985 into the VECTOR R&D Amalgamation, which received a federal status in 1994. It includes 6 specialized R&D institutes (of molecular biology, aerobiology, bioengineering, cell structures, biologically active substances and collections of cultures of microorganisms), a WHO Cooperation Center and a nursery for lab animals. Taken together, this represents one of the world's biggest R&D institutions specializing in this field. Its staff of more than 1,300 includes a full and a corresponding member of the RAS, 18 doctors and 153 candidates of sciences.
The past few years have seen a significant expansion of the range of basic studies by the Center scientists. This now covers the structure and functions of genomes of pathogenic viruses, their evolution and disease control and prevention. Theoretical and experimental studies are also under way into the mechanisms of variability of pathogenic viruses and appropriate disease prevention methods.
VECTOR experts are focusing on the development and utilization of biotechnological methods (including genetic engineering) for the production of curative, preventive and diagnostic preparations of new generations. This also covers related ecological studies.
A state-of-the-art R&D base of the Center formed over the past 25 years is unrivalled not only in this, but also in other member states of the former Soviet Union. It makes it possible to ensure complete safety both for the staff and the environment even when dealing with viruses and viral infections for which there is still no cure now, such as hemorrhagic or Congo-Crimean fevers, and infections caused by the Ebola, Lassa and Marburg viruses, natural smallpox, etc.
The progress achieved by the Center's scientists in all of these areas is quite impressive. They obtained, for example, earlier than their foreign counterparts, data on the structural-functional organization of the genomes of the Marburg, Ebola and natural smallpox viruses and fully decoded their primary structure. Basic studies at the Center have put its scientists on the verge of complete understanding of the very nature of the above ailments and the possible mechanisms of their prevention. The scientists have been able to trace the evolution of the viruses, which led them to the conclusion that, for example, the causative agent of smallpox has been "inherited" by humans from domestic animals.
Another major area of research conducted by the Center is the development of vaccine against AIDS. The original approach suggested by local scientists consists in trying to develop a cure in the form of a protein with a preset spatial structure.
The past few years have seen the appearance of many viruses and their strains with modified antigen and other biological properties which makes the existing vaccines less effective and reduces the sensitivity of the accepted diagnostic procedures. For a molecular-biological analysis of these pathogenes VECTOR scientists have amassed a representative collection of blood samples from AIDS patients, and patients with measles and A and С hepatitis. Studies of these samples provide data on the variations of these pathogenes leading to the devel-
opment of diagnostic preparations of a new generation and offering essential guides for the development of new vaccines.
The Center also boasts a collection of more than 20 thousand samples of cultures of microorganisms which received an international ECCO status in 1995. VECTOR scientists also have at their disposal a steadily growing bank of cell structures which is essential for basic and applied research in this area and for the production of immunobiological preparations. These are tested on laboratory animals, including primates, which are kept and bred at the local nursery.
Another major area of research conducted by VECTOR scientists are ecological studies, including numerous methods of analysis of the environment and a whole range of sampling devices with preset parameters. Deserving of special mention is an effective air sampling method with the intake of air particles and their subsequent separation by aerodynamic parameters. Bioaerosols are tested by a unique method of biological particles polarization in a magnetic field. And the Center's scientists have also developed a system of medicobiological monitoring with automatic data processing for regions with adverse ecological conditions. At the same time they have isolated and described microorganisms which can proliferate in media containing petroleum products and toluene (hydrocarbon obtained from coal tar). Apart from that, local scientists have isolated by selection a Zoogloea SP strain, which can proliferate at high concentrations of copper and be used as a basis for the development of a biosorbent of heavy metals.
As was mentioned before, the Center's scientists are engaged in a comprehensive program of applied research for the development of medical preparations on the basis of modern technologies, including genetic engineering. They have synthesized a unique preparation, called Calcytonin, which can cure disorders caused by upsets of body calcium exchange (such as hyper-
calciemya of different origins, acute dystrophy of bones, osteoporosis and slow healing of fractures after accidents or surgeries). Another novelty is the preparation Desmopresin used for the treatment of non-sugar diabetes and nocturnal enuresis. It can also be widely used for boosting blood coagulation in patients with certain forms of hemophilia. The newly-developed strains have made it possible to develop hemogenic eritropoetin, antiviral subalin, an effective antitumor remedy and a vaccine against В hepatitis.
Using some original technologies, VECTOR scientists have pioneered some non-traditional forms of a number of medicinal preparations and vaccines. New vaccines against measles and hepatitis, for example, can be produced in the form of tablets, which is important since the peroral administration of drugs does away with the threat of viral infections through injections.
Deserving of special mention at this point are two medical preparations developed over the past three years, which are of special importance for people in this country. One of them is Ridostin (inductor of interferon), which possesses immunostimulating and antiviral action. The drug is effective against herpetic lesions (smallpox, shingles), Acarina encephalitis, influenza and bacterial infections leading to blood poisoning.
Another new drug is an effective vaccine against hepatitis A, which can considerably reduce its propagation. Both of these new preparations have passed federal tests and have been cleared for hospital use by the Ministry of Public Health of the Russian Federation.
Another recent achievement of VECTOR scientists is a new method of making preparations for hemodialysis (method of therapy of acute and chronic kidney insufficiency with the help of an artificial kidney machine).
Apart from medical preparations, the Center's scientists have launched the production of biochemical reagents for laboratory studies. This includes nucleic acid enzymes, nutrient media and serums for the cultivation of cells and viruses (more than 60 varieties), etc. The list of such preparations now exceeds 300.
The VECTOR Center also has a separate unit for the clinical tests of its products with up-to-date facilities and equipment. Taking part in such tests are only volunteers in keeping with WHO requirements, and the building is also used for the treatment of patients with dangerous infections.
VECTOR specialists are actively involved in a range of scientific- and-technical programs of different levels. The most important of them are the federal Program "Availability of Medicines in Russia", a program of the Moscow Government, the RF Ministry of Industry, Science and Technologies entitled "Development and Introduction into Medical Practice of New Methods of Cancer Diagnostics and Treatment" and federal programs like "Human Genome", "Latest Methods of Bioengineering", "Combatting the Most Common Diseases (AIDS)", and "Priority Areas of Genetics". In 1997 the Center was awarded a Government Prize in Science and Technology for the development and organization of production of new and highly-effective methods of diagnostics of AIDS and hepatites А, В and C. The award also covers the development of home-made interferon in the year 2000.
Bearing in mind the leading position of VECTOR in Russia in the field of virology and molecular biology, the Government decided in 1994 to set up on its basis a national collection of strains of smallpox virus. A program of studies of this virus was adopted in 1995 and approved by the WHO in 1997, and in Koltsovo there appeared the world's second (after the United States) museum of strains and DNA of the smallpox virus.
Siberian scientists working in this area of research are cooperating with some of the leading institutes and labs of the United States, Germany and France. In 1997 VECTOR presentations were carried out in Poland, India, Vietnam, Cambodia and Finland.
The international rank of this unique research center is demonstrated by the fact that its projects are financed not only by the Russian Foundation for Fundamental Studies, but also by the International Scientific and Technical Center, the American Foundation for Civil Studies, and the US Power Engineering Ministry.
All these achievements of VECTOR would have been impossible without its highly skilled specialists who are keeping abreast of the latest methods of research in virology, molecular biology and genetic engineering in addition to a wealth of practical experience in dealing with especially dangerous infections. And there is a constant inflow of young blood from most of this country's leading universities which have close professional links with VECTOR, such as the Novosibirsk State University (Department of Natural Sciences), Novosibirsk State Agrarian University and the Siberian State Medical University (in Tomsk).
A total of more than 14 doctoral theses and more than 120 theses for the degree of candidate of sciences have been defended since the opening in 1983 of the school of post-graduate studies in molecular biology, virology and biotechnology. The emphasis there is on
the integration of science and education and a special Program is being developed now for maintaining an uninterrupted "chain" of specialist training: school - college - post-graduate studies.
In the early 1990s some of the VECTOR subdivisions received an independent status as the manufacturers of high-quality medical, pharmaceutical, cosmetological and veterinary products and equipment matching international standards.
One of the first of them was ZAO VECTOR-BEST, set up in 1992, which concentrates on the production of effective diagnostic and therapeutical equipment for public health care. Its staff of more than 300 includes one doctor and 18 candidates of sciences. Their skills backed by up-to-date technical equipment have made the firm a national leader in the development and production of state- of-the-art testing systems. The firm now puts on the market more than 120 such systems for diagnostics of AIDS, viral hepatitis, tuberculosis and other ailments. The firm also produces more than 20 tons of sets of reagents a month (of some 50 types) for clinical and biochemical studies.
One especially impressive fact about VECTOR-BEST is that its output of diagnostic products covers about 35 percent of the CIS market requirements and by the range of its products the firm is one of the leaders in this country. The quality of its testing systems is monitored on a permanent basis by the Tarasevich State Institute of Standardization and Control of Medical Immunobiological Preparations, the State Institute of Standardization and Control of Medicines and the Central Research Institute of Venerology.
The list of pioneering achievements of the Center includes an express test for AIDS, diagnostic sets for identification of syphilis (using home-made proteins), for measuring the blood level of hemoglobin (excluding the traditional use of toxic cyanides), etc. VECTOR-BEST products are in good demand not only in Russia
and other CIS countries, but also in Poland, India, Argentina, Brazil, China and countries of South-East Asia.
Apart from its independent activities, ZAO is cooperating with VECTOR on a range of programs and projects, including, for example, the development of an International Center for studies of the existing and new infections, a program of theoretical and applied research of tuberculosis and in the implementation of a project on organizing production of means of diagnostics of viral fevers under the WHO auspices.
Another outcrop of VECTOR bears the name of ImDi. It was set up in 1993 for the development, improvement and introduction into commercial use of up-to-date medical diagnostic methods and establishment of joint ventures with Russian and foreign partners. At the present time ImDi turns out some 39 types of testing systems mainly for users in Russia and Kazakhstan. Plans for the near future provide for boosting the output to 10 thousand sets per month and for opening of an analysis lab.
The year 1999 saw the birth of yet another VECTOR offspring - VECTOR-FARM State Unitary Production Enterprise. The efforts of its staff of 240 members, including 10 candidates of sciences, are focused on preparing for commercial production of curative, prophylactic and diagnostic preparations supplied by the Center. Two main lines of production are already in operation-ready medicines (of more than 50 kinds) and new immuno-biological preparations. By the volume of output VECTOR-FARM belongs to the 20 leading firms in this country.
The VECTOR-BiAlgam R&D Company was set up in 1998 as a producer of curative and preventive preparations and dietetic products on the basis of eubiotics (intestinal bacteria) and for the development of new technologies of production of medicinal preparations from blood plasma. The firm is now producing bifido- containing preparations which are effectively used for the treatment and prevention of infections and malignancies, gastro- intestinal, nervous and circulatory disorders. It is also running a farm for Japanese quails - the only one of its kind in this country- whose eggs are used for the production of new immunobiological preparations. Despite its tender age, the farm has already won 8 gold medals at different specialized fairs in the Siberian region for the development of new bifido-containing products. And the firm is also producing a vaccine against hepatitis A.
Another local producer of a somewhat different kind is the Siberian Natural Cosmetics R&D Center. Founded in 1992, the firm supplies the domestic market with inexpensive high-quality cosmetics based on biologically active substances with the addition of extracts of propolis, May birch leaves, bird cherry, currant and also benzoic acid contained in foxberry and cranberry. Apart from vegetable additives, wide use is also made of sperm and caviar of sea urchins, mussels, gonads of sea combs, DNA fragments from salmon milt, enzymes of collagenase (from the liver of Far Eastern crabs) and hyaluronidase, etc.
Products of the Siberian Natural Cosmetics are in good demand, which is also demonstrated by diplomas and medals (total of 18, including 7 gold ones) awarded at shows in this and other countries.
Interest in Siberian cosmetics has been shown by a number of foreign firms, including Nerrays (USA), Franco-Russe de Distribution (France), CMS Cosmedi and Deutsche Bank. Under a contract with the German firm Gala Premium this company is a representative of the Siberian Natural Cosmetics in Europe. Under an agreement with the International Development Partners (USA), the latter is the exclusive representative of the Siberian Natural Cosmetics on the American continent and is now looking for partners to set up a joint venture.
The next on our list is the BioProPlus R&D firm set up in 1998. Its speciality are fodder additives for cattle and veterinary preparations. The firm is now operating in conjunction with the PLIVA Company (Croatia). The main users of the company products are pig and poultry farms, milk farms and the like.
Our survey of Koltsovo would be incomplete without a glimpse of the Inorganic Chemistry R&D Center specializing in advanced technologies of pure metals production, electric-plasma systems (vacuum and high-pressure units of up to 10 mW) and modern electrothermal equipment of its own design for a range of applications - in the atomic industry, metallurgy, engineering and construction (energy-saving coatings).
One of the major achievements of the Center is the development of technological processes and equipment for the production of high-grade germanium. The first stage of this plant was put into operation in the year 2000 and the whole project will have an output of 600 kg of this metal a month. Objectives for the future include the production of high-purity helium, rubidium, cesium and scandium for this country's industrial needs.
Summing it up, one can say that the town of Koltsovo with the VECTOR Center as its core has lived up to its makers' expectations and even surpassed them. The achievements of basic and applied research in molecular biology, virology, genetic engi-
neering, epidemiology, biotechnology and other areas have received recognition in this and many other countries. The school of scientific research formed here over the past quarter of a century has won international acclaim as has been demonstrated by the victory in the TAG IS international contest "Centers of Advanced Research and Scientific Innovations".
Plans for the future of Koltsovo and its research and commercial infrastructure are reflected in a comprehensive Development Program for the years 2001-2006. It provides, for example, for the establishment of an International Medical Center for the studies of the existing and new infections and a supercomputer complex for an effective analysis of chromosomes within the framework of the Human Genome International Program.
Another priority objective on this list is the establishment of a Center of Innovations, which would render a whole range of services for the organization and development of science-intensive areas of production - from an original concept to mass production and marketing.
Work will continue on streamlining the organization of production of medicinal preparations and equipment-from vaccines against hepatites A and В to new technologies for making disposable clothing and bedding for hospital use.
The Program also covers cosmetology, veterinary products and ecologically pure technologies.
A special section of the Program takes care of research and development in the field of disease prevention and treatment and medical education as well as the development of the urban infrastructure and the social sphere.
The Program is to be translated into life in three stages. At the first stage (2001-2002), organizational, legal and economic mechanisms will be established as the basis for progress in the strategic fields of Koltsovo as a"naukograd" - science town. Some of the new commercial projects will also be launched at that stage. At the second stage (2002-2005), an expected new level of urban growth and development will be put into practice. At the third stage (2006) the science town and its residents will up grade the stable socio-economic status on a sustainable basis.
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