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
Examples of diseases often mentioned in the context of biological warfare Human diseases Smallpox Cholera Shigellosis Botulism SEB intoxication Animal diseases Zoonoses Anthrax Brucellosis Coccidioidomycosis EEE / VEE / WEE Japanese B Ebola/Marburg Histoplasmosis Melioidosis Glanders Plague Psittacosis Q Fever Rabies Tularemia African Swine Fever Foot and Mouth Fowl Plague Newcastle Rinderpest
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
Implications and Constraints for the Weaponeer • Must be presented as a respirable aerosol It follows therefore that. . . • 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
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
Biological Terrorism and Public Health Chemical Terrorism HAZMAT EVENT------------------PUBLIC HEALTH PROBLEM Biological Terrorism
Outbreak or Epidemic ? Anthrax (and most others) Plague Smallpox Day 0
Outbreak or Epidemic ? Anthrax (and most others) Plague Smallpox Day 10
Outbreak or Epidemic ? Anthrax (and most others) Plague Smallpox Day 20
Outbreak or Epidemic ? Anthrax (and most others) Plague Smallpox Day 30
Outbreak or Epidemic ? Anthrax (and most others) Plague Smallpox Day 40
The “Unique” Threat • Dual-Use Nature • Evolving Technology • Political Factors
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
Technological Change Could Make Biological Warfare a Moving Target Genomics Proteomics Automated Sequencing Cloning Transfection Polymerase Chain Reaction Altered agent Tropism Production methods Enhanced Stability Access to technologies and information is getting easier
The Moscow Times Thursday, January 20, 1994 Yeltsin Names Core of New Government Ruble Falls and Rush Continues Funds Disappearing
Cold-War Solutions • Vaccines, Drugs and Diagnostics • Environmental Sensors and Masks • The Biological Weapons Convention
The Biological Threat has Changed Cold War Gulf War Tactical use on the battlefield …. and strategic use against the U. S. Today… & Tomorrow? “Terrorist” use against the force or our cities
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 make it easier 3 But, fortunately, it’s still not easy to do
The Biological Terrorist Spectrum Likelihood of Occurrence • Many Agents • Individual/Group • Classical Agents • State Sponsorship Hoaxes Non-Mass Casualty Devices/Agents Numbers of Casualties Mass Casualty Devices/Agents
The Biological Terrorist Spectrum Likelihood of Occurrence • Many Agents • Individual/Group • Classical Agents • State Sponsorship Hoaxes 1997: 27 hoaxes Non-Mass Casualty Since then: ca. 200/yr Mass Casualty Devices/Agents October 2001: > Thousands Devices/Agents 1987: Salmonella on salad bar…. now B. anthracis Numbers of Casualties None
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)
The Challenge of Environmental Detection • Logistics (e. g. . power and reagents) • Sensitivity • Background Interference • Timeliness Detect to Warn or Detect to Treat
Bill Patrick’s Relative Aerosol Potency Chart Agent Q Fever Tularemia VEE Anthrax SEB Botulinum A Nerve Agent VX Respiratory Dose for Man (ug) 0. 0000021 0. 0004 0. 008 0. 025 4. 5 8, 000 -More infective -More Toxic
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 ID 50 10 100 1, 000 10, 000 Human. 6 org/100 l 6 org/10 l 6 org/l 60 org/ l Sensor Reqmt. 10 org/100 l 10 org/10 l 10 org/ l 100 org/l Note: The human must see 10 orgs to retain 6 100 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)
The Challenge of Timely Diagnostics • Sample collection • Sample preparation (clean-up) • Complex matrices/background • Accurate differentiation • Miniaturization Reasonable Goals: • Sample Prep in <5 min • Gene Amplification and Detection in <25 min
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
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
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 Since 9 -11 …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
The Way Ahead 3 Surveillance (diagnostics and communication) 3 Education 3 Proactive Deterrence 3 Public Health Infrastructure 3 HUMINT 3 Biomedical Research
The Way Ahead 3 Surveillance (diagnostics and communication) 3 Education 3 Proactive Deterrence 3 Public Health Infrastructure It’s not about: 3 HUMINT - Suits 3 Biomedical Research - Masks - Decon Stations It’s Public Health
The Way Ahead 3 Surveillance (diagnostics and communication) 3 Education 3 Proactive Deterrence 3 Public Health Infrastructure 3 HUMINT But it’s not JUST Public Health…. 3 Biomedical Research It’s Public Health (+)
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
The Future …challenges and potential solutions
The last 5 -6 years: Rapid Change 3 3 3 3 Nonprolif. Focus PCMs MCMs Intel Surveillance Analysis Complexity Experts Mgt Research $ Treaties……………. . Cooperative Threat Reduction Cold-War defense…. . Domestic Preparedness Do. D masks……………New clothing technologies Specific Vaccines…. . Diagnostics, Drugs, Generic CMs Humint………………. Masint and Threat Analysis Nuclear………………. Bio Do. D………………. . …Do. D/CDC/Do. J/Do. E…State and Local Low…………………. . . High Few…………………. . (Many) Do. D………………. …. HHS, FEMA, Do. J $ Do. D……………. . $/ HHS, Do. J, Do. D, Do. E, IC $137 M in Do. D in ‘ 97. . $11 B Nationally in ‘ 03 Education Do. D…………. Do. D, Do. J, HHS, Academia, Industry The Enemy Soviet Union (80 s)…. . State and Non-state actors Collaborators Allies…………………. . Russian Colleagues Hoaxes Almost none…………. Routine……. . Overwhelming Interest Low…………………. . High……. . Extremely High
“Wish List” for the Future 3 3 3 3 Nonprolif. PCMs Detection MCMs Triage Intel Surveillance Management Leadership Education Regulatory Research Hoaxes Policy “Trust” pills In-place oro-nasal “filter” and non-invs. Ind. exposure alarm Simple, cheap, generic, integrated……. . dual-use Pre-clinical diagnostic, Generic therapeutic drugs Within-4 hr minimally invasive “triage machine” “Intent” meter Satellite-based, high sensitivity, immediate Educated, objective Mission oriented; willing to take responsibility/share results CB “M. A. S. H. ” of Seinfield Series…. . The “anthrax” letters Effective FDA teaming…. . we’re getting there Risk-benefit based, dual-use, basic Airplane hijacking model? …. but this is more difficult Swift retaliation and extreme measures
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