Current Thought on Bioterrorism:Current Thought on Bioterrorism: The Threat, Preparedness and Response

Office of Basic Energy SciencesWorkshop on

Basic Research Needs toCounter Terrorism

February 28 - March 1, 2002Gaithersburg, MD 20878

David R. Franz, DVM, Ph.DDavid R. Franz, DVM, Ph.DSouthern Research InstituteSouthern Research Institute

University of Alabama at BirminghamUniversity of Alabama at Birmingham

Examples of diseases often Examples of diseases often mentioned in the context of mentioned in the context of

biological warfare biological warfare Human diseases

SmallpoxCholeraShigellosis Anthrax

BrucellosisCoccidioidomycosisEEE / VEE / WEEJapanese B Ebola/MarburgHistoplasmosis

Animal diseases

African Swine FeverFoot and MouthFowl PlagueNewcastleRinderpest

MelioidosisGlandersPlaguePsittacosisQ FeverRabiesTularemia

Zoonoses

BotulismSEB intoxication

B.W. Agents Differ from C.W. AgentsB.W. Agents Differ from C.W. Agents

Biological Agents

NaturalProduction difficultNone volatileMany toxins more toxicInfectious agents replicateNot dermally activeLegitimate medical useOdorless and tastelessDiverse pathogenic effectsMany are effective immunogensAerosol deliveryDelayed Onset (Days to Weeks)A few are contagious

Chemical Agents

Man-madeProduction difficult (industrial)Many volatileLess toxic than many toxinsDo not replicateMany are dermally activeNo use other than as weaponsOdor or taste when contaminatedFewer types of effectsPoor immunogensMist / droplet / aerosol deliveryRapid Onset (Minutes)Not Contagious

Implications and Constraints for the Implications and Constraints for the WeaponeerWeaponeer

• 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...

Implications for Public HealthImplications 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

HAZMAT EVENT-----------------------------------PUBLIC HEALTH PROBLEM

Chemical Terrorism

Biological Terrorism

Biological Terrorism and Public Health

Anthrax(and most others)

Plague Smallpox

Outbreak or Epidemic ?

Day 0

Plague Smallpox

Outbreak or Epidemic ?

Day 10

Anthrax(and most others)

Plague Smallpox

Outbreak or Epidemic ?

Day 20

Anthrax(and most others)

Plague Smallpox

Outbreak or Epidemic ?

Day 30

Anthrax(and most others)

Plague Smallpox

Outbreak or Epidemic ?

Day 40

Anthrax(and most others)

The “Unique” ThreatThe “Unique” Threat

• Dual-Use Nature

• Evolving Technology

• Political Factors

Expression of cereolysine AB Expression of cereolysine AB genes in genes in Bacillus anthracisBacillus anthracis

vaccine strain ensures protection vaccine strain ensures protection against experimental hemolytic against experimental hemolytic

anthrax infectionanthrax infection A.P. Pomerantsev, N.A. Staritsin, Yu. V. Mockov and L.I. Marinin

….results describe the modulation of immunopathogenic properties ofB. anthracis due to expression of cereolysin AB genes.

Vaccine. Vol 15, 1997

Technological Change Could Make Biological Warfare a Moving Target

GenomicsProteomicsAutomated SequencingCloningTransfectionPolymerase Chain Reaction

Access to technologies and information is getting easier

Altered agent TropismProduction methodsEnhanced Stability

The Moscow The Moscow TimesTimes

Thursday, January 20, 1994Thursday, January 20, 1994

Yeltsin Names Core of New Government

Ruble Fallsand RushContinues

Funds Disappearing

Cold-War SolutionsCold-War Solutions

• Vaccines, Drugs and Diagnostics

• Environmental Sensors and Masks

• The Biological Weapons Convention

The Biological Threat The Biological Threat has Changedhas Changed

Tactical use onthe battlefield….and strategicuse against the U.S.

“Terrorist” use againstthe force or our cities

Cold War Gulf War Today… & Tomorrow?

Why Bioterrorism in the US Today?Why Bioterrorism in the US Today?

We’re the nation to beatThey can’t do it conventionallyLooking for a great equalizerBiological warfare expertise is availableDual-use nature makes it hard to detectWe’re still vulnerableBiotechnology may make it easierBut, fortunately, it’s still not easy to do

The Biological Terrorist SpectrumThe Biological Terrorist SpectrumL

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Mass CasualtyMass Casualty Devices/AgentsDevices/Agents

Numbers of CasualtiesNumbers of Casualties

HoaxesHoaxes

•Classical AgentsClassical Agents•State SponsorshipState Sponsorship

•Many AgentsMany Agents•Individual/GroupIndividual/Group

Non-Mass CasualtyNon-Mass Casualty Devices/AgentsDevices/Agents

The Biological Terrorist SpectrumThe Biological Terrorist SpectrumL

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Mass CasualtyMass Casualty Devices/AgentsDevices/Agents

Numbers of CasualtiesNumbers of Casualties

HoaxesHoaxes

•Classical AgentsClassical Agents•State SponsorshipState Sponsorship

•Many AgentsMany Agents•Individual/GroupIndividual/Group

Non-Mass CasualtyNon-Mass Casualty Devices/AgentsDevices/Agents

1997: 27 hoaxesSince then: ca. 200/yrOctober 2001: > Thousands

1987: Salmonella onsalad bar….now B. anthracis

None

Tools for Identification of Tools for Identification of Biological agentsBiological 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 EnvironmentalThe Challenge of EnvironmentalDetectionDetection

• Logistics (e.g.. power and reagents)

• Sensitivity

• Background Interference

• Timeliness

Detect to Warn orDetect to Treat

Bill Patrick’s Relative Aerosol Bill Patrick’s Relative Aerosol Potency ChartPotency Chart

Agent Respiratory Dose for Man (ug)

Q Fever 0.0000021Tularemia 0.0001VEE 0.0004Anthrax 0.008SEB 0.025Botulinum A 4.5Nerve Agent VX 8,000

-More infective-More Toxic

Detector Sensitivity Detector Sensitivity RequirementsRequirements

IF…...ID50 is 100 organismsAND..Aerosol retention is 60%AND..Minute volume is 10 litersAND..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)

ID50 Human. Sensor Reqmt.10 6 org/100 l 10 org/100 l100 6 org/10 l 10 org/10 l1,000 6 org/l 10 org/ l10,000 60 org/ l 100 org/l

Note: The human must see 10 orgs to retain 6

The Challenge of Timely The Challenge of Timely DiagnosticsDiagnostics

• Sample collection

• Sample preparation (clean-up)

• Complex matrices/background

• Accurate differentiation

• MiniaturizationReasonable Goals:• Sample Prep in <5min• Gene Amplification and Detection in <25min

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 enoughMilitary and Publicpreparedness is a

deterrent

The New, Multivalent Threat:The New, Multivalent Threat:Reducing ProliferationReducing 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 maylook like the 1999 West

Nile Outbreak

What has changed…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?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

The Way AheadThe Way Ahead

Surveillance (diagnostics and communication)EducationProactive DeterrencePublic Health InfrastructureHUMINTBiomedical Research

The Way AheadThe Way Ahead

Surveillance (diagnostics and communication)EducationProactive DeterrencePublic Health InfrastructureHUMINTBiomedical Research

It’s not about: - Suits - Masks - Decon StationsIt’s Public Health

The Way AheadThe Way Ahead

Surveillance (diagnostics and communication)EducationProactive DeterrencePublic Health InfrastructureHUMINTBiomedical Research

But it’s not JUST Public Health….

It’s Public Health (+)

Bioterrorism: Lessons Learned Bioterrorism: Lessons Learned

Think Public Health (plus)Think Dual-use InvestmentsThink Tech-base not MaterielThink EducationThink Cost-BenefitThink Long-Term

The FutureThe Future

…challenges and potential …challenges and potential solutionssolutions

The last 5-6 years: The last 5-6 years: Rapid ChangeRapid Change Nonprolif. Treaties……………..Cooperative Threat Reduction Focus Cold-War defense…..Domestic Preparedness PCMs DoD masks……………New clothing technologies MCMs Specific Vaccines…..Diagnostics, Drugs, Generic CMs Intel Humint……………….Masint and Threat Analysis Surveillance Nuclear……………….Bio Analysis DoD………………..…DoD/CDC/DoJ/DoE…State and Local Complexity Low…………………...High Experts Few…………………..(Many) Mgt DoD……………….….HHS, FEMA, DoJ Research $ $\ DoD……………....$/ HHS, DoJ, DoD, DoE, IC

$137M in DoD in ‘97..$11B Nationally in ‘03 Education DoD………….……….DoD, DoJ, HHS, Academia,

Industry The Enemy Soviet Union (80s)…..State and Non-state actors Collaborators Allies…………………..Russian Colleagues Hoaxes Almost none………….Routine……..Overwhelming Interest Low…………………....High……..Extremely High

““Wish List” for the FutureWish List” for the Future Nonprolif. “Trust” pills PCMs In-place oro-nasal “filter” and non-invs. Ind. exposure alarm Detection Simple, cheap, generic, integrated……..dual-use MCMs Pre-clinical diagnostic, Generic therapeutic drugs Triage Within-4hr minimally invasive “triage machine” Intel “Intent” meter Surveillance Satellite-based, high sensitivity, immediate Management Educated, objective Leadership Mission oriented; willing to take responsibility/share results Education CB “M.A.S.H.” of Seinfield Series…..The “anthrax” letters Regulatory Effective FDA teaming…..we’re getting there Research Risk-benefit based, dual-use, basic Hoaxes Airplane hijacking model?….but this is more difficult Policy Swift retaliation and extreme measures