Development Of A Network Of International Centers To
Combat Infectious Diseases And Bioterrorism Threats
Sergey V. Netesov, Lev S.
The threat of biological weapons and their use in bioterrorism have increased. At the same time there are huge improvements in the knowledge of infectious diseases. How do we contain the threat of biological warfare (BW) and bioterrorism and continue to make progress in eliminating and treating infectious diseases? What role can Russia play in this containment?
Russias great writer Anthon Chekhov wrote once that " There is no national science different from an international one, as there is no national multiplication table " This idea is perfectly illustrated by infectious diseases, which cover continents, cross national borders, and have no respect for either prosperity or poverty. Infectious diseases are global; their diagnoses, prophylaxes and treatments are effective when they are part of a global effort. The survival and development of humanity depends on our ability to fight and treat infectious diseases globally.
There is a new level of comprehension of infectious disease dangers along with our increased understanding of the science, medical treatment and social consequences, especially in developed countries [1-4]. This understanding of infectious agents has evolved to appreciate their dynamically changing properties, including such critical characteristics as pathogenicity, antigenic structure, and drug resistance. In the past 20 years, more than 30 previously unknown infectious agents, causing such diseases as AIDS, hemorrhagic fevers, antibiotic resistant bacterial strains, hepatitis C, etc., have been identified. A significant part of these infectious diseases result from the ability of microorganisms to mutate and adapt to humans and their medical treatment environment of medical prophylaxes and treatments. These properties, combined with increasing human mobility and migration and the increasing number of people with suppressed immunity, and several other factors, make the emergence of new diseases and variants more likely.
BW Nonproliferation and Threat Reduction
The issues of nonproliferation and threat reduction of biological weapons based on infectious agents are different from other weapons of mass destruction (WMD). These issues are complicated by the general occurrence of pathogens in nature, the continual emergence of new variants of human pathogenic microorganisms and the availability of public health data on the effects of these agents on the human population in different regions of the world. Specific microbial strains and disease incidence data may have the potential for misuse. However, we believe that the major nonproliferation and threat reduction efforts should focus on already working with emerging pathogens research centers, which might present a source of expertise for potential bioterrorists.
American scientists and WHO experts proposed to join efforts of different nations to create a global network for infectious diseases surveillance and control [3,5]. At the initial phase, they proposed as many as 15 international centers in the key regions of the world. These centers would coordinate their activities with WHO, with the leading centers in the US and European countries, and with relevant national authorities responsible for public health issues. How or to what extent can Russia be involved in international collaboration in infectious disease research? This has no simple answer because there are still some continuing elements of mistrust in certain circles in the US and in other Western countries [12-15]. The worry is that Russia might use international collaboration and Western financial support for possible illicit activities. According to John Holum, US Arms Control and Disarmament Agency Director, there are at least 12 countries that have undeclared offensive BW development programs. However, we strongly believe that Russia now is not a subject of concern to experts involved in compliance with the 1972 BTWC.
Russia has done significant legislative work to strengthen her compliance with the regime of the 1972 BW Convention, the guidelines of the Australia Group and the BTWC Review Conferences:
Russias Role in Infectious Disease Research and International Cooperation
Russia has great potential in the area of infectious disease research, as well as in development and manufacture of therapeutic and prophylactic preparations at facilities of the Russian Ministry of Public Health, those of BIOPREPARAT and of local public health establishments. Two large State Research Centers of the Russian Ministry of Public Health for Applied Microbiology (Obolensk, European region) and Virology and Biotechnology VECTOR (Koltsovo, eastern region) were involved in biological defense programs of the former Soviet Union before 1990. Consequently they have years of experience in bacterial and viral pathogen research. With their technical and staff capabilities they could play a significant role within a global network for infectious diseases control. VECTOR fully follows the Russian guidelines and forwards annual reports to the Committee on the Biological and Chemical Weapons Conventions compliance at the office of the Russian president. These reports are the documents that are envisaged by the Review Conference of the 1972 BW Convention for subsequent submission to the UN.
Through the Russian Ministry of Science and Technologies, the Russian Ministry of Public Health and RAO "BIOPREPARAT", both the Obolensk and Koltsovo Centers are actively involved in broad international collaborations. These collaborations are under such organizations as International Science and Technology Center (ISTC, EC+USA+Japan), US National Academy of Sciences (NAS), Association for the Promotion of Cooperation with Scientists from New Independent States of the FSU (INTAS, EC), Civilian Research and Development Foundation (CRDF, USA), Initiatives for Proliferation Prevention (IPP-DOE, USA), National Aeronautics and Space Administration (NASA, USA), Defense Advanced Research Projects Agency (DARPA, USA). These international collaborations are aimed at nonproliferation and threat reduction by strengthening the confidence building measures and transparency, but do not involve dual use technologies.
In 1997 an expert group of the US National Academy of Sciences (NAS) under the leadership of Prof. Joshua Lederberg and Dr. John Steinbruner, with the involvement of Russian experts, developed a concept for international collaboration in dangerous pathogen research . This concept uses confidence building measures and transparency extensively. In particular, each project would have freedom of access at the place of performance and all results are to be provided to all counterparts. Collaborative work between Russian and US scientists would be carried out in laboratories of these countries under a separate agreement. This freedom of access is also defined in programs such as CRDF, NASA, DARPA and IPP (DOE).
While these cooperative programs are effective, they are limited. These programs have involved only a part of our personnel and do not fully employ the most qualified staff and the high containment laboratories, which are of the main concern to experts. The six pilot projects concluded under the NAS initiative, for example, used only five percent of our available staff and high containment areas.
Recently, we have been actively discussing this issue with experts from the Russian Ministry of Public Health, the Russian Ministry of Science and Technologies, as well as with our colleagues from different US agencies, ISTC and those from the International Research Center "The Joint Institute for Nuclear Research" in Dubna, Moscow Oblast, Russian Federation . We believe International Centers in Russia for the study of viral (Koltsovo) and bacterial (Obolensk) pathogens will serve the interests of nonproliferation and worldwide public health. We also believe it is very important that WHO, as an international public health authority, be involved early in this process to discuss the feasibility and to develop the concept of these International Centers.
By International Center, we mean an international organization established by an intergovernmental agreement, similar to those of the ISTC or the Joint Institute for Nuclear Research in Dubna, or CERN in Switzerland. Nonproliferation and threat reduction can only be achieved through transparency and confidence building when International Centers are established and operated with free access to the program and the results obtained, and with free access to all facilities and all staff. Continuous involvement of foreign scientists in work at these centers is a powerful instrument of confidence building. It is critical that ALL high containment capabilities and supporting facilities are incorporated into the International Center to alleviate concerns over possible illicit activity.
The State Research Center of Virology and Biotechnology VECTOR, operated by the Russian Ministry of Public Health, is a large research and production complex, whose primary activities are focused on basic and applied research in the theoretical virology, molecular biology, virology, immunology, aerobiology, epidemiology, and biotechnology. VECTOR also develops and manufactures preventive, therapeutical and diagnostic preparations.
VECTOR is one of two scientific and experimental facilities in Russia mainly focusing on virus infection research. The State Research Center for Applied Microbiology, Russian Ministry of Public Health (Obolensk, Moscow Oblast), is a similar scientific and experimental center, involved in bacterial infections research. VECTOR and Obolensk are the only institutions in both Russia and the rest of the CIS countries in which studies of highly dangerous pathogens can be done at an up-to-date level. Data on capabilities of our two Centers are available in the INTERNET .
VECTORs research and production facilities amount to more than 250,000 m2 on over 8,000 hectares (19,768 acres). The research and experimental facilities at VECTOR are equipped for up-to-date scientific work with highly pathogenic human and animal viruses, under conditions of complete biosafety. Several buildings meet special biosafety requirements for high containment facilities (BSL 2, 3, and 4): an air-tight external perimeter, negative pressure in the working zone, complete sterilization (liquid, and solid) or reliable filtration (air) of all types of discharge.
Currently there are 2,098 employees at VECTOR. The research and technical staff of the Center (1,200) are highly qualified personnel, specializing in the field of genetic engineering, molecular biology, virology, theoretical virology, immunology, epidemiology, and ecology. The staff has extensive experience in highly dangerous viruses research and in production of diagnostic and prophylactic preparations for public health and veterinary needs. Of the 340 researchers, 157 have Candidate (Ph.D. equivalent) and Doctor of Sciences degrees.
The Collection of Cultures of Microorganisms in VECTOR contains over 10,000 deposit entries: various viral strains, including the national collection of variola virus strains and strains of BSL-4 viral pathogens; recombinant viral strains; strains of microorganisms, including producer strains. The Collection received international recognition in 1995 when it was affiliated with the European Culture Collection Organization (ECCO). VECTOR also houses one of the two WHO Collaborating Centers for orthopoxvirus diagnosis and repository for variola virus strains and their DNA. The other WHO Collaborating Center for smallpox and other poxvirus infections is at the CDC in Atlanta, USA. As a WHO Collaborating Center, VECTOR preserves and studies the Russian collection of variola virus isolates. The research collaboration between these two Centers is promising in terms of basic science and confidence building.
VECTORs Breeding and Holding Facility for laboratory animals, which includes one of only two monkey breeding facilities operating in Russia, is used for testing therapeutic and diagnostic preparations. Facilities for the performance of preclinical and clinical trials of new medicinal preparations are available at VECTOR.
The Center has a long-term experience in ecology research. VECTORs Institute of Aerobiology actively participated in studying the environmental situation in different cities of Kuzbass coal mines region and developed recommendations for reducing pollution there. This Institute continues this study using modern and unique tailor-made equipment and modern mathematical methods. VECTOR houses a Chair of Basic Medicine of the Novosibirsk State University, which will make it possible to involve students and undergraduates in research work of the International Center.
The Novosibirsk Regional Center for the Prophylaxis and Prevention against AIDS, is located on VECTORs grounds in a specialized clinical isolation department equipped in accordance with BSL-3 requirements.
Possible Research Programs
Possible research at the proposed International Center could focus on arboviruses, including tick-borne encephalitis virus that is endemic in Russia; HFRS virus, Omsk hemorrhagic fever virus both endemic in Siberia; filoviruses: Marburg and Ebola; orthopoxviruses: smallpox virus, monkeypox, and cowpox viruses; viruses causing hepatitis A, B, C; paramyxoviruses, rabdoviruses, influenza viruses, etc. This list of viruses could be extended by bacteria and parasites, such as tuberculosis, which is increasing sharply now in Russia, and opisthorchiasis human parasitic disease affecting the liver. The latter is endemic in Siberia, too.
Scientific programs of the proposed International Center can be based on recommendations contained in the Controlling Dangerous Pathogens report of US NAS . Research areas should cover fundamental aspects of genetics, physiology, and biochemistry of pathogens; pathogenesis studies, including those on human immune response to an infectious disease; development of diagnostic methods; development of drugs and vaccines; epidemiological studies, including the investigation of environmental factors and their effect on rodents and insects; the effect of human behavior and demography, etc.
Special attention would be paid to the investigation of the mass outbreaks of infectious diseases in the region (Asian part of Russia, Central Asian republics members of C.I.S., and possibly other countries of the region). We propose using molecular epidemiology, determining the sero- and genotypes of infectious agents, possible source of primary infection, and even to help distinguishing whether an outbreak is intentional or not. Such investigations may be made on regular basis for a wide list of pathogens and would be extremely useful for monitoring of the evolution of infectious agents. As a result of this research, the proposed International Center could have as one of its strategic scientific goals making prognoses, based on the data from global monitoring, of what new infections might emerge in the future.
It is important that the Centers staff enroll in various training and exchange programs, that the Center invite foreign scientists for research work at the Centers, and that our scientists get training abroad. Of course, these are only some baselines for possible scientific programs if the proposed International Centers are established.
Though the process of establishing the International Centers is complex and will take several years, the proposed relationship provides for a long-term strategic collaboration, which is far less subject to political or economic conjuncture fluctuations in Member States.
International efforts will accelerate both the study of dangerous pathogens and the development of state-of the-art public health products for diagnosis, prophylaxis and therapy.
The proposed International Centers will allow us to join efforts to control potential bioterrorists. It is, however, important to establish a regime of an appropriate dissemination and use of the scientific results obtained that might facilitate possible misuse of biological agents.
The proposed International Centers will create zones of openness and transparency to efficiently serve the purposes of nonproliferation, cooperative threat reduction, and emergency preparedness.
The proposed International Centers can provide modern fast diagnostics and monitoring of infectious disease agents in the vast territory of East Europe and Northern Asia. This would be extremely helpful for the prognosis of evolution and emergence of infectious diseases endemic to the area.
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4. EMC Annual Report 1996, World Health Organization, 1997
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6. Decree of the Russian President on ensuring the fulfillment of international obligations in the area of biological weapons, Decree 1 390, April 11, 1992
7. Procedures for controlling the export from Russian Federation of disease agents, their genetically altered forms, and fragments of genetic material that can be used for developing bacteriological (biological) and toxin weapons, Nov. 20, 1992, Decision RG 1 892
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14. W. Orent. Escape from Moscow, The Sciences, May 22, 1998, p. 26-31
ASA 99-1, Issue no. 70
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