Center for International and Security Studies at Maryland1 Qualitative and Quantitative Assessment of the “Dangerous Activities” Categories Jens H. Kuhn July 2005 CISSM School of Public Policy This paper was prepared as part of the Advanced Methods of Cooperative Security Program at the Center 4113 Van Munching Hall for International and Security Studies at Maryland, with generous support from the MacArthur Foundation University of Maryland and the Sloan Foundation. College Park, MD 20742 Tel: (301) 405-7601 [email protected] 2 QUALITATIVE AND QUANTITATIVE ASSESSMENT OF THE “DANGEROUS ACTIVITIES” CATEGORIES DEFINED BY THE CISSM CONTROLLING DANGEROUS PATHOGENS PROJECT WORKING PAPER (July 31, 2005) Jens H. Kuhn, MD, ScD (Med. Sci.), MS (Biochem.) Contact Address: New England Primate Research Center Department of Microbiology and Molecular Genetics Harvard Medical School 1 Pine Hill Drive Southborough, MA 01772-9102, USA Phone: (508) 786-3326 Fax: (508) 786-3317 Email: [email protected] 3 OBJECTIVE The Controlling Dangerous Pathogens Project of the Center for International Security Studies at Maryland (CISSM) outlines a prototype oversight system for ongoing microbiological research to control its possible misapplication. This so-called Biological Research Security System (BRSS) foresees the creation of regional, national, and international oversight bodies that review, approve, or reject those proposed microbiological research projects that would fit three BRSS-defined categories: Potentially Dangerous Activities (PDA), Moderately Dangerous Activities (MDA), and Extremely Dangerous Activities (EDA). It is the objective of this working paper to assess these categories qualitatively and quantitatively. To do so, published US research of the years 2000-present (early- to mid-2005) will be screened for science reports that would have fallen under the proposed oversight system had it existed already. Qualitatively, these selective reports will be sorted according to the subcategories of each individual Dangerous Activity, broken down by microbiological agent, and year. Quantitatively, institutes and researchers, which conducted research that would have fallen under review by BRSS, will be listed according to category and year. Taken together, the results of this survey will give an overview of the number of research projects, institutes, and researchers that would have been affected had the new proposed system existed, and thus should allow estimating the potential impact of BRSS on US microbiological academic and industrial research in the future. Furthermore, this working paper might aid refining the proposed system. 4 INTRODUCTION Over the last years, the number of scientific advances and inventions has increased exponentially. To date, there is no effective mechanism to evaluate the potential implications of the ever-growing number of scientific experiments. Benign and legitimate research might lead to results, which, in the wrong hands, could be misused to threaten entire human, animal, or plant populations. This holds true especially for microbiological and genomic research. Recently, a prototype oversight system (“Controlling Dangerous Pathogens Project”) has been proposed by a working group of the Center for International Security Studies at Maryland (CISSM). This Biological Research Security System (BRSS) aims to achieve more protection against deliberate or inadvertent misapplication of microbiological research.1 BRSS envisions complementing the 1972 Biological Toxins and Weapons Convention. It is supposed to be legally binding to countries that would choose to abide to the system, which foresees the creation of international, national, and regional governmental oversight bodies. It is impossible to survey the complete microbiological literature on a regular basis. However, certain experiments are more likely to yield results that could be misused than others. Similarly, certain microbiological agents are more likely to be considered for illegitimate purposes than others. The Controlling Dangerous Pathogens Project has established three categories, which outline the most critical research to be controlled. These Potentially Dangerous Activities (PDA), Moderately Dangerous Activities (MDA), and Extremely Dangerous Activities 1 Steinbruner, John, Elisa D. Harris, Nancy Gallagher, and Stacy Gunther. 2003. Controlling Dangerous Pathogens: A Prototype Protective Oversight System. Center for International Security Studies at Maryland, USA. [Online.] http://www.cissm.umd.edu/documents/pathogensmonograph.pdf 5 (EDA) would be monitored by the governmental oversight bodies. These Dangerous Activities are currently defined as follows: Potentially Dangerous Activities (PDA): 1. Work with listed agent— or exempt avirulent, attenuated, or vaccine strain of select agent — not covered by EDA/MDA 2. Increasing virulence of non-listed agent 3. Increasing transmissibility or environmental stability of non-listed agent 4. Powder or aerosol production of non-listed agent 5. Powder or aerosol dispersal of non-listed agent 6. De novo synthesis of non-listed agent 7. Genome transfer, genome replacement, or cellular reconstitution of non-listed agent Moderately Dangerous Activities (MDA): 1. Increasing virulence of listed agent or related agent 2. Insertion of host genes into listed agent or related agent 3. Increasing transmissibility or environmental stability of listed agent or related agent 4. Powder or aerosol production of listed agent or related agent 5. Powder or aerosol dispersal of listed agent or related agent 6. De novo synthesis of listed agent or related agent 7. Construction of antibiotic- or vaccine-resistant related agent 8. Genome transfer, genome replacement, or cellular reconstitution of listed agent or related agent Extremely Dangerous Activities (EDA):1 1. Work with eradicated agent (eradicated agent includes work with the 1918 Influenza A virus, derivatives of the 1918 Influenza A virus, and chimeric influenza virus with at least one gene from the 1918 Influenza A virus) 1 In a previous version of the Controlling Dangerous Pathogens Project’s categories, an EDA subcategory “Work with revived extinct agent related to listed agent” was included. The author suggests to reintroduce this subcategory, because such work is potentially dangerous; and scientific success has been achieved in this field by US groups (e.g. the revival of ancient Bacillus, Halobacterium, and other bacterial strains from amber and other materials). 6 2. Work with agent requiring Biosafety Level-4 3. De novo synthesis of eradicated agent/agent requiring Biosafety Level-4 4. Expanding host range of agent to new host (in humans, other animals and plants) or changing the tissue range of a listed agent 5. Construction of antibiotic- or vaccine-resistant listed agent For these categories, an “agent” has been defined as a “fungus, protist, rickettsia, bacterium, virus, viroid, or prion; or genetic element, recombinant nucleic acid, or recombinant organism”. A “listed agent” has been defined as an “agent on [the] CDC Select Agent list, USDA High-Consequence Livestock Pathogens list, or USDA/APHIS/PPQ Plant Pathogens list” with the exception of toxins. The Centers for Disease Control and Prevention (CDC) Select Agent and US Department of Agriculture (USDA) High-Consequence Livestock Pathogens lists overlap.1 The agents that are listed on the three different lists are, in alphabetical order, the following: CDC/DHSS NON-OVERLAP SELECT AGENTS2 - Crimean-Congo hemorrhagic fever virus - Coccidioides posadasii - Cercopithecine herpesvirus 1 - Filoviruses - Kyasanur forest disease virus - Lassa virus - Monkeypox virus - Omsk hemorrhagic fever virus - Rickettsia prowazekii - Rickettsia rickettsii - South American hemorrhagic fever viruses (Flexal virus, Guanarito virus, Junín virus, Machupo virus, Sabiá virus) - Tick-borne encephalitis virus (Far Eastern, and Western European subtypes) - Variola virus 1 [Online.] http://www.aphis.usda.gov/programs/ag_selectagent/index.html, and http://www.cdc.gov/od/sap/docs/salist.pdf. 2 The list has been modified to fit the current taxonomy of the listed agents (see Method section). 7 - Yersinia pestis HIGH CONSEQUENCE LIVESTOCK PATHOGENS/SELECT AGENTS (OVERLAP AGENTS) - Bacillus anthracis - Brucella melitensis (strains abortus, melitensis, and suis) - Burkholderia mallei - Burkholderia pseudomallei - Clostridium botulinum (neurotoxin-producing) - Coccidioides immitis - Coxiella burnetii - Eastern equine encephalitis virus - henipaviruses - Francisella tularensis - Rift Valley fever virus - Venezuelan equine encephalitis virus USDA HIGH CONSEQUENCE LIVESTOCK PATHOGENS (NON-OVERLAP AGENTS) - African horse sickness virus - Akabane virus - Alcelaphine herpesvirus 1,2 (formerly known as Malignant catarrhal fever viruses, exotic strains only) - African swine fever virus - Bluetongue virus (exotic) - Bovine spongiform encephalopathy prion - Camelpox virus - Classical swine fever virus - Ehrlichia ruminantium (formerly known as Cowdria ruminantium) - Foot-and-mouth disease virus - Goatpox virus - Human enterovirus B (strain Human coxsackievirus B5 (formerly Swine vesicular disease virus) - Lumpy skin disease virus - Influenza A virus (avian highly pathogenic strains; eradicated agent according to table above) - Japanese encephalitis virus - Menangle virus 8 - Mycoplasma capricolum - Mycoplasma mycoides capri - Mycoplasma mycoides mycoides - Newcastle disease virus - Peste-des-petits-ruminants virus - Rinderpest virus - Sheeppox virus