1. What will be studied? What are the risks? Part II October 1, 2007 National Emerging Infectious Diseases Laboratories

2. Presenters Mark Klempner, MD Associate Provost for Research Director, NEIDL Institute Jack Murphy, PhD Professor of Medicine and Microbiology Chief, Section of Molecular Medicine Co-Director, NEIDL Institute

3. Category A: Bacillus anthracis (anthrax) Clostridium botulinum Yersinia pestis (plague) Francisella tularensis (tularemia) Variola major (smallpox) and other pox viruses (smallpox virus can only be studied at the CDC BSL-4 facility by international convention – and will not be studied at the NEIDL) Viral Hemorrhagic fevers Arenaviruses LCM, Junin, Machupo, Guanarito, Lassa Bunyaviruses Hantaviruses Rift Valley Fever Flaviviruses Dengue Filoviruses Ebola, Marburg The NEIDL will study NIAID Category A, B, & C agents

4. Category B: Burkolderia pseudomallei (meliodosis Coxiella burnetii (Q fever) Brucella sp. (glanders) Ricin toxin Epsilon toxin (Clostridium perfringes) Typhus fever (Rickettsia prowazeki) Food and Water-borne Pathogens Diarrheagenic Escherichia coli Pathogenic Vibrios (e.g., V. cholerae) Shigella sp. Salmonella sp. Listeria monocytogenes Campylobacter jejuni Yersinia entercolitica Viruses Calciviruses Hepatitis A Protozoa Cryptosporidium parvum Cyclospora cayatenensis Giardia lamblia Entamoeba histolytica Toxoplasma Microsporidia Other viruses West Nile virus LaCross California encephalitis Venezuelan equine encephalitis Western equine encephalitis Japanese encephalitis virus Kyasanur forest virus The NEIDL will study NIAID Category A, B, & C agents

5. Category C: Emerging infectious diseases Nipah virus Hantaviruses (other) Tickborne hemorrhagic viruses Crimean Congo hemorrhagic fever virus Tickborne encephalitic viruses Yellow fever Multi-drug resistant Mycobacterium tuberculosis Influenza Other Rickettsias Rabies The NEIDL will study NIAID Category A, B, & C agents

6. The following agents must be studied under BSL-4 containment. 1) Central European tick-borne encephalitis 2) Congo-Crimean hemorrhagic fever 3) Ebola 4) Guanarito 5) Hendra/Nipah 6) Junin 7) Kyasanur Forest disease 8) Lassa 9) Machupo 10) Marburg 11) Omsk hemorrhagic fever 12) Russian Spring-Summer encephalitis 13) Sabia http://www4.od.nih.gov/oba/rac/guidelines/guidelines.html

7. Smallpox - by international convention smallpox can only be studied in the U.S. at the CDC BSL-4 laboratory in Atlanta, Georgia Monkey B virus - there is only one laboratory that has been contracted by the NIH to study Monkey B virus – Georgia State University, Atlanta, Georgia BSL-4 agents that will not be studied at the NEIDL

8. Who has the BSL-4 expertise & what will they study when the NEIDL opens? Dr. Tom Geisbert – Ebola, Marburg, Lassa, Nipah (likely) Dr. Tom Geisbert – Ebola, Marburg, Lassa, Nipah (likely) ~ 20 years experience working at BSL-4; work has lead to prototype vaccine for Ebola Joan Geisbert – Ebola, Marburg, Lassa, Nipah (likely) Joan Geisbert – Ebola, Marburg, Lassa, Nipah (likely) ~ 25 years experience working at BSL-4; work has involved the training of most all BSL-4 investigators in the U.S. and has assisted in development of prototype vaccine for Ebola Dr. Elke Muhlenberger – Ebola, Marburg, Nipah (likely) Dr. Elke Muhlenberger – Ebola, Marburg, Nipah (likely) ~ 15 years experience working at BSL-4; work has focused on the molecular biology of Ebola and Marburg virus

9. What are the risks to the community from the NEIDL? MaterialForm Community Risk 1 hemorrhagic fever viruses liquid negligible – transmission by intimate contact with infected bodily fluids 2 anthraxliquid negligible – liquid contains spore dispersion 3 tularemialiquid negligible - no person to person spread 4 MDR tuberculosisliquid Negligible from the NEIDL – agent is already in the community 5 Protein Toxins (e.g., botulinum, ricin) liquid negligible – “chemical”

10. There are many safeguards to minimize risks to protect the community Building system and design Experienced BSL-4 investigators have & are being recruited Rigorous safety and security Standard Operating Procedures (SOPs) that must be followed by researchers Agents are stored as frozen liquid in inventoried small volumes Single vial thawed for individual experiments

11. ■ Limited access to the NEIDL and security checks of persons and property ■ Collaborative Training Programs with city agencies ■ Integration of staff and knowledge with BMC clinicians ■ Institutional Biosafety Committee oversight of all experimental protocols ■ Boston Public Health Commission regulations & oversight ■ Massachusetts Department of Public Health ■ NIH and CDC guidelines, regulations & oversight There are many safeguards to minimize risks to protect the community

12. How do we decide what will be studied in the NEIDL? ■ Expertise of investigators who have been and will be recruited to the NEIDL institute ■ Programmatic initiatives instituted by the NEIDL (e.g., MDR-tuberculosis) ■ Ongoing research programs at BUMC which require high containment laboratories (e.g., tularemia) ■ The funding of research grant submissions to support individual research programs in the NEIDL ■ Regulatory approval of individual research programs and protocols by both institutional committees (e.g., IBC) and Boston Public Health Commission

13. How Will the Community Know What’s Being Studied? Institutional Biosafety Committee (public representation) NEIDL Institute Executive Committee (public representative) NEIDL External Scientific Advisory Committee Boston Public Health Commission Community Liaison Committee Mass. Department of Public Safety

14. The NEIDL is Accountable to Independent Public Health and Safety Officials LOCAL Institutional Biosafety Committee Boston Public Health Commission Boston Fire Department Boston Inspectional Services Boston Water and Sewer Commission STATE Massachusetts Department of Public Health Massachusetts Department of Environmental Protection Massachusetts Water Resources Authority FEDERAL Centers for Disease Control U.S. Department of Transportation U.S. Environmental Protection Agency Occupational Health & Safety Administration National Institutes of Health U.S. Department of Agriculture Nuclear Regulatory Commission

15. Q & A