1. Current Thought on Bioterrorism: The Threat, Preparedness and Response Office of Basic Energy Sciences Workshop on Basic Research Needs to Counter Terrorism February 28 - March 1, 2002 Gaithersburg, MD 20878 David R. Franz, DVM, Ph.D Southern Research Institute University of Alabama at Birmingham

2. Examples of diseases often mentioned in the context of biological warfare Human diseases Smallpox Cholera Shigellosis Anthrax Brucellosis Coccidioidomycosis EEE / VEE / WEE Japanese B Ebola/Marburg Histoplasmosis Animal diseases African Swine Fever Foot and Mouth Fowl Plague Newcastle Rinderpest Melioidosis Glanders Plague Psittacosis Q Fever Rabies Tularemia Zoonoses Botulism SEB intoxication

3. B.W. Agents Differ from C.W. Agents Biological Agents Natural Production difficult None volatile Many toxins more toxic Infectious agents replicate Not dermally active Legitimate medical use Odorless and tasteless Diverse pathogenic effects Many are effective immunogens Aerosol delivery Delayed Onset (Days to Weeks) A few are contagious Chemical Agents Man-made Production difficult (industrial) Many volatile Less toxic than many toxins Do not replicate Many are dermally active No use other than as weapons Odor or taste when contaminated Fewer types of effects Poor immunogens Mist / droplet / aerosol delivery Rapid Onset (Minutes) Not Contagious

4. Implications and Constraints for the Weaponeer Must be presented as a respirable aerosol Preparation and weaponization may jeopardize viability Aerosols are dependant on meteorological conditions However... Contagious agents can be delivered without weaponization Some agents can be spread by vectors It follows therefore that...

5. Implications for Public Health Many diseases begin as “flu-like illness” Definitive diagnostics are specific and complex Treatment after clinical diagnosis may be too late Preclinical diagnostics are not generally available Few antiviral drugs available Vaccines are very specific and require years to field Prophylaxis may be socially or politically unacceptable Potential for complex psychological response

6. HAZMAT EVENT-----------------------------------PUBLIC HEALTH PROBLEM Chemical Terrorism Biological Terrorism Biological Terrorism and Public Health

7. Anthrax (and most others) Plague Smallpox Outbreak or Epidemic ? Day 0

8. Plague Smallpox Outbreak or Epidemic ? Day 10 Anthrax (and most others)

9. Plague Smallpox Outbreak or Epidemic ? Day 20 Anthrax (and most others)

10. Plague Smallpox Outbreak or Epidemic ? Day 30 Anthrax (and most others)

11. Plague Smallpox Outbreak or Epidemic ? Day 40 Anthrax (and most others)

12. The “Unique” Threat Dual-Use Nature Evolving Technology Political Factors

13. Expression of cereolysine AB genes in Bacillus anthracis vaccine strain ensures protection against experimental hemolytic anthrax infection A.P. Pomerantsev, N.A. Staritsin, Yu. V. Mockov and L.I. Marinin ….results describe the modulation of immunopathogenic properties of B. anthracis due to expression of cereolysin AB genes. Vaccine. Vol 15, 1997

14. Technological Change Could Make Biological Warfare a Moving Target Genomics Proteomics Automated Sequencing Cloning Transfection Polymerase Chain Reaction Access to technologies and information is getting easier Altered agent Tropism Production methods Enhanced Stability

15. The Moscow Times Thursday, January 20, 1994 Yeltsin Names Core of New Government Ruble Falls and Rush Continues Funds Disappearing

16. Cold-War Solutions Vaccines, Drugs and Diagnostics Environmental Sensors and Masks The Biological Weapons Convention

17. The Biological Threat has Changed Tactical use on the battlefield ….and strategic use against the U.S. “Terrorist” use against the force or our cities Cold WarGulf WarToday… & Tomorrow?

18. Why Bioterrorism in the US Today? 3 We’re the nation to beat 3 They can’t do it conventionally 3 Looking for a great equalizer 3 Biological warfare expertise is available 3 Dual-use nature makes it hard to detect 3 We’re still vulnerable 3 Biotechnology may make it easier 3 But, fortunately, it’s still not easy to do

19. The Biological Terrorist Spectrum Likelihood of Occurrence Mass Casualty Devices/Agents Devices/Agents Numbers of Casualties Hoaxes Classical AgentsClassical Agents State SponsorshipState Sponsorship Many AgentsMany Agents Individual/GroupIndividual/Group Non-Mass Casualty Devices/Agents Devices/Agents

20. The Biological Terrorist Spectrum Likelihood of Occurrence Mass Casualty Devices/Agents Devices/Agents Numbers of Casualties Hoaxes Classical AgentsClassical Agents State SponsorshipState Sponsorship Many AgentsMany Agents Individual/GroupIndividual/Group Non-Mass Casualty Devices/Agents Devices/Agents 1997: 27 hoaxes Since then: ca. 200/yr October 2001: > Thousands 1987: Salmonella on salad bar….now B. anthracis None

21. Tools for Identification of Biological agents Culture and Isolation (1 - 30 days) Animal Inoculation (2 - 30 days) Immunoassays (2 - 6 hours) Nucleic Acid Assays (3 - 5 hours) Mass Spectroscopy (1 - 8 hours)

22. The Challenge of Environmental Detection Logistics (e.g.. power and reagents) Sensitivity Background Interference Timeliness Detect to Warn or Detect to Treat

23. Bill Patrick’s Relative Aerosol Potency Chart AgentRespiratory Dose for Man (ug) Q Fever0.0000021 Tularemia0.0001 VEE0.0004 Anthrax0.008 SEB0.025 Botulinum A4.5 Nerve Agent VX 8,000 -More infective -More Toxic

24. Detector Sensitivity Requirements IF…...ID 50 is 100 organisms AND..Aerosol retention is 60% AND..Minute volume is 10 liters AND..Cloud is on site for 10 min 100 org X 60% = 60 org 10 l /min X 10 min = 100 liters Must detect 60 org in 100 liters OR 0.6 org/liter (or 6 organisms / 10 liters) ID 50 Human. Sensor Reqmt. 106 org/100 l 10 org/100 l 1006 org/10 l 10 org/10 l 1,0006 org/l 10 org/ l 10,00060 org/ l 100 org/l Note: The human must see 10 orgs to retain 6

25. The Challenge of Timely Diagnostics Sample collection Sample preparation (clean-up) Complex matrices/background Accurate differentiation Miniaturization Reasonable Goals: Sample Prep in <5min Gene Amplification and Detection in <25min

26. Complexity of the Problem Targets may be military, civilian or both Threat footprint may be very small It may appear to be a naturally occurring disease Attribution will not always be possible Fundamentally, it’s a public health problem Materiel solutions alone are not enough Military and Public preparedness is a deterrent

27. The New, Multivalent Threat: Reducing Proliferation The New, Multivalent Threat: Reducing Proliferation NO SINGLE APPROACH FOR ALL SITUATIONS Russia Current economic weakness provides threat reduction options China A growing world-power in biotechnology; the great unknown Smaller threat nations Many may be capable of producing effective biological weapons Subnational Groups….or individuals? The new threat may look like the 1999 West Nile Outbreak

28. What has changed… Something related to “intent to harm” New diseases added to physician differentials Public understanding of the biological threat Funding for Bioterrorism Preparedness National...and apparently international...will And even, thought of immunizing the population …and what hasn’t? The technical difficulty of agent preparation The importance of meteorology to the attacker The difficulty of intelligence collection The value of Public Health for preparedness The value of our Science and Technology base The value of Education Since 9-11

29. The Way Ahead 3 Surveillance (diagnostics and communication) 3 Education 3 Proactive Deterrence 3 Public Health Infrastructure 3 HUMINT 3 Biomedical Research

30. The Way Ahead 3 Surveillance (diagnostics and communication) 3 Education 3 Proactive Deterrence 3 Public Health Infrastructure 3 HUMINT 3 Biomedical Research It’s not about: - Suits - Masks - Decon Stations It’s Public Health

31. The Way Ahead 3 Surveillance (diagnostics and communication) 3 Education 3 Proactive Deterrence 3 Public Health Infrastructure 3 HUMINT 3 Biomedical Research But it’s not JUST Public Health…. It’s Public Health (+)

32. Bioterrorism: Lessons Learned 3 Think Public Health (plus) 3 Think Dual-use Investments 3 Think Tech-base not Materiel 3 Think Education 3 Think Cost-Benefit 3 Think Long-Term

33. The Future …challenges and potential solutions

34. The last 5-6 years: Rapid Change 3 Nonprolif.Treaties……………..Cooperative Threat Reduction 3 FocusCold-War defense…..Domestic Preparedness 3 PCMsDoD masks……………New clothing technologies 3 MCMsSpecific Vaccines…..Diagnostics, Drugs, Generic CMs 3 IntelHumint……………….Masint and Threat Analysis 3 SurveillanceNuclear……………….Bio 3 AnalysisDoD………………..…DoD/CDC/DoJ/DoE…State and Local 3 Complexity Low…………………...High 3 ExpertsFew…………………..(Many) 3 MgtDoD……………….….HHS, FEMA, DoJ 3 Research $$\ DoD……………....$/ HHS, DoJ, DoD, DoE, IC $137M in DoD in ‘97..$11B Nationally in ‘03 3 EducationDoD………….……….DoD, DoJ, HHS, Academia, Industry 3 The EnemySoviet Union (80s)…..State and Non-state actors 3 CollaboratorsAllies…………………..Russian Colleagues 3 HoaxesAlmost none………….Routine……..Overwhelming 3 InterestLow…………………....High……..Extremely High

35. “Wish List” for the Future 3 Nonprolif.“Trust” pills 3 PCMsIn-place oro-nasal “filter” and non-invs. Ind. exposure alarm 3 DetectionSimple, cheap, generic, integrated……..dual-use 3 MCMsPre-clinical diagnostic, Generic therapeutic drugs 3 TriageWithin-4hr minimally invasive “triage machine” 3 Intel“Intent” meter 3 SurveillanceSatellite-based, high sensitivity, immediate 3 ManagementEducated, objective 3 LeadershipMission oriented; willing to take responsibility/share results 3 EducationCB “M.A.S.H.” of Seinfield Series…..The “anthrax” letters 3 RegulatoryEffective FDA teaming…..we’re getting there 3 ResearchRisk-benefit based, dual-use, basic 3 HoaxesAirplane hijacking model?….but this is more difficult 3 PolicySwift retaliation and extreme measures