U.S. Air Force Research LaboratoryHuman Effectiveness Directorate

Cooperative Agreement FA8650-05-2-6523

U.S. Air Force Research LaboratoryU.S. Air Force Research LaboratoryHuman Effectiveness DirectorateHuman Effectiveness Directorate

Cooperative Agreement FA8650Cooperative Agreement FA8650--0505--22--65236523

_______________________ _______________________

Dr. Larry RegensUniversity of Oklahoma Health Sciences Center

Dr. Larry RegensDr. Larry RegensUniversity of Oklahoma Health Sciences CenterUniversity of Oklahoma Health Sciences Center

Science and Technology for Chem-Bio Information Systems

Albuquerque, NM25-28 October 2005

Science and Technology for Science and Technology for ChemChem--Bio Bio Information SystemsInformation Systems

Albuquerque, NMAlbuquerque, NM2525--28 October 2005 28 October 2005

Advances in Biotechnology and the Biosciences

for Warfighter Performance and Protection

Advances in Biotechnology and the Advances in Biotechnology and the Biosciences Biosciences

for Warfighter Performance and for Warfighter Performance and ProtectionProtection

Description of Effort

Focus on terrorist attempts to expose humans to aerosol releases of bacterial, viral, and toxin agents

Project elements designed to expand knowledge, tools, models, and strategies

Includes international collaboration with scientists in Israel and Russian Federation

Description of EffortDescription of Effort

Focus on terrorist attempts to Focus on terrorist attempts to expose humans to aerosol expose humans to aerosol releases of bacterial, viral, and releases of bacterial, viral, and toxin agents toxin agents

Project elements designed to Project elements designed to expand knowledge, tools, expand knowledge, tools, models, and strategiesmodels, and strategies

Includes international Includes international collaboration with scientists in collaboration with scientists in Israel and Russian FederationIsrael and Russian Federation

(b)

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Objective

Support Defense Threat Reduction Agency efforts to advance state-of-the-art in high-visibility area of paramount national importance by enhancing deterrence, detection, preparedness, response, and recovery from CBRNE terrorism

ObjectiveObjective

Support Defense Threat Reduction Agency Support Defense Threat Reduction Agency efforts to advance stateefforts to advance state--ofof--thethe--art in highart in high--visibility area of paramount national visibility area of paramount national importance by enhancing deterrence, importance by enhancing deterrence, detection, preparedness, response, and detection, preparedness, response, and recovery from CBRNE terrorism recovery from CBRNE terrorism

Benefits to Warfighter

Protect the Nation against terrorism and provide NORTHCOM and CENTCOM capabilities to support national incident response and support US forces fighting terrorism overseas

Benefits to WarfighterBenefits to Warfighter

Protect the Nation against terrorism and Protect the Nation against terrorism and provide NORTHCOM and CENTCOM provide NORTHCOM and CENTCOM capabilities to support national incident capabilities to support national incident response and support US forces fighting response and support US forces fighting terrorism overseasterrorism overseas

Engages a Broad-Based Interdisciplinary Team for Research Effort

Engages a BroadEngages a Broad--Based Interdisciplinary Team Based Interdisciplinary Team for Research Effortfor Research Effort

Projects concentrate on four areas:

Biomedical ApplicationsThreat CharacterizationConsequence Management Behavioral Dynamics

Projects concentrate on four areas:Projects concentrate on four areas:

Biomedical ApplicationsBiomedical ApplicationsThreat CharacterizationThreat CharacterizationConsequence Management Consequence Management Behavioral DynamicsBehavioral Dynamics● ●

MicrobiologyMicrobiology

Industrial HygieneIndustrial Hygiene

Policy AnalysisPolicy Analysis

EmergencyMedicineEmergencyMedicine

EngineeringEngineeringEnvironmentalHealth ScienceEnvironmentalHealth Science

PsychiatryPsychiatry

BIOMEDICAL APPLICATIONSBIOMEDICAL APPLICATIONSBIOMEDICAL APPLICATIONS

Key Challenge: Identify and model cell type-specific, cytotoxic effects and mechanism of lethality

Key Challenge: Identify Key Challenge: Identify and model cell typeand model cell type--specific, cytotoxic effects specific, cytotoxic effects and mechanism of lethalityand mechanism of lethality

Electron photography of sections of murine lungs with deposited soot particles. Magnification about 20,000.

Electron photography of sections of Electron photography of sections of murine lungs with deposited soot murine lungs with deposited soot particles. Magnification about 20,000.particles. Magnification about 20,000.

Laboratory Studies to Investigate Cytotoxicity and Immunological

ConsequencesCell and microorganism interactions (microorganism detection and diagnostics)Immunology (antivirals and immune system stimulants/suppressors)Therapeutics

Laboratory Studies to Investigate Laboratory Studies to Investigate Cytotoxicity and Immunological Cytotoxicity and Immunological

ConsequencesConsequencesCell and microorganism Cell and microorganism interactions (microorganism interactions (microorganism detection and diagnostics)detection and diagnostics)Immunology (antivirals and Immunology (antivirals and immune system immune system stimulants/suppressors)stimulants/suppressors)TherapeuticsTherapeutics

MAJOR GOALS

Short-Term: Define molecular and cellular mechanisms of ET-induced cell death for possible development of therapeutics. Most research and therapeutics designed to treat late stage effects of anthrax focus on blocking LT protein complex due to assumption LT is the major virulence factor. Recent OUHSC study has found that ET is cytotoxic to mammalian cells and is more effect killer of cells than LT.

Long-Term: Determine combined effects of ET and LT on cell physiology in order to develop the first comprehensive model of anthrax toxin’s collective impact on mammalian cells. Total impact of anthrax toxin on developing embryos will be determined to make predictions about possible birth defects in infants from women exposed to B. anthracis to support diagnosis, vaccines, immunology, and therapeutics.

MAJOR GOALSMAJOR GOALS

ShortShort--Term: Define molecular and cellular Term: Define molecular and cellular mechanisms of ETmechanisms of ET--induced cell death for induced cell death for possible development of therapeutics. Most possible development of therapeutics. Most research and therapeutics designed to treat research and therapeutics designed to treat late stage effects of anthrax focus on late stage effects of anthrax focus on blocking LT protein complex due to blocking LT protein complex due to assumption LT is the major virulence factor. assumption LT is the major virulence factor. Recent OUHSC study has found that ET is Recent OUHSC study has found that ET is cytotoxic to mammalian cells and is more cytotoxic to mammalian cells and is more effect killer of cells than LT.effect killer of cells than LT.

LongLong--Term: Determine combined effects of Term: Determine combined effects of ET and LT on cell physiology in order to ET and LT on cell physiology in order to develop the first comprehensive model of develop the first comprehensive model of anthrax toxinanthrax toxin’’s collective impact on s collective impact on mammalian cells. Total impact of anthrax mammalian cells. Total impact of anthrax toxin on developing embryos will be toxin on developing embryos will be determined to make predictions about determined to make predictions about possible birth defects in infants from women possible birth defects in infants from women exposed to B. anthracis to support diagnosis, exposed to B. anthracis to support diagnosis, vaccines, immunology, and therapeutics. vaccines, immunology, and therapeutics.

THREAT CHARACTERIZATIONTHREAT CHARACTERIZATIONTHREAT CHARACTERIZATION

2 4 6 8 10

(b) 45 -- 50 40 -- 45 35 -- 40 30 -- 35 25 -- 30 20 -- 25 15 -- 20 10 -- 15 5.0 -- 10 0 -- 5.0 Key Challenge: Model

dispersion, estimate human exposures, and assess risk of aerosol releases for in-door and ambient environments

Key Challenge: Model Key Challenge: Model dispersion, estimate human dispersion, estimate human exposures, and assess risk of exposures, and assess risk of aerosol releases for inaerosol releases for in--door and door and ambient environmentsambient environments

Modeling and Simulation to Investigate Bioaerosol

DispersionAerosol propagation (direct, inverse, statistical)Methods for aerosol samplingand detectionMeasurement of particle deposition in respiratory tract

Modeling and Simulation to Modeling and Simulation to Investigate Bioaerosol Investigate Bioaerosol

DispersionDispersionAerosol propagation (direct, Aerosol propagation (direct, inverse, statistical)inverse, statistical)Methods for aerosol samplingMethods for aerosol samplingand detectionand detectionMeasurement of particle Measurement of particle deposition in respiratory tractdeposition in respiratory tract

MAJOR GOALS

Short-Term: Develop integrated develop computational fluid dynamic (CFD) predictive models of B. anthracis spore inhalation, transport, and deposition for physiologically accurate 3-dimensional representation of adult male, adult female, and child respiratory tract.

Long-Term: Verify predictive models via laboratory experiments with representative simulants and morphologically accurate human respiratory tract airway replicas to support differential exposure-risk assessment. Exposure-dose curves for pulmonary deposition of B. anthracis spores in adult males, adult females, and young children under physiologically realistic breathing conditions will provide basis for infection risk assessment for various exposure scenarios and enable more effective consequence management.

MAJOR GOALSMAJOR GOALS

ShortShort--Term: Develop integrated develop Term: Develop integrated develop computational fluid dynamic (CFD) predictive computational fluid dynamic (CFD) predictive models of B. anthracis spore inhalation, transport, models of B. anthracis spore inhalation, transport, and deposition for physiologically accurate 3and deposition for physiologically accurate 3--dimensional representation of adult male, adult dimensional representation of adult male, adult female, and child respiratory tract.female, and child respiratory tract.

LongLong--Term: Verify predictive models via Term: Verify predictive models via laboratory experiments with representative laboratory experiments with representative simulants and morphologically accurate human simulants and morphologically accurate human respiratory tract airway replicas to support respiratory tract airway replicas to support differential exposuredifferential exposure--risk assessment. Exposurerisk assessment. Exposure--dose curves for pulmonary deposition of B. dose curves for pulmonary deposition of B. anthracis spores in adult males, adult females, anthracis spores in adult males, adult females, and young children under physiologically realistic and young children under physiologically realistic breathing conditions will provide basis for breathing conditions will provide basis for infection risk assessment for various exposure infection risk assessment for various exposure scenarios and enable more effective consequence scenarios and enable more effective consequence management. management.

Posterior ViewPosterior View

Left Side Left Side

Prototype Computer Model of Tracheobronchial Portion of

Male Respiratory Tract

Prototype Computer Model of Prototype Computer Model of TracheobronchialTracheobronchial Portion of Portion of

Male Respiratory TractMale Respiratory Tract

CONSEQUENCE MANAGEMENTCONSEQUENCE MANAGEMENTCONSEQUENCE MANAGEMENT

Key Challenge: Delineate information requirements and knowledge transfer mechanisms for effective emergency medical systems

Key Challenge: Delineate Key Challenge: Delineate information requirements information requirements and knowledge transfer and knowledge transfer mechanisms for effective mechanisms for effective emergency medical systemsemergency medical systems

Investigate Strategies for Effective Preparedness and Response

Models of system capabilities for mass casualty incidentsPredictors of responseLessons learned from prior incidents to enhance resilienceCollaboration with Israel National Center for Trauma and Emergency Medicine Research

Investigate Strategies for Effective Investigate Strategies for Effective Preparedness and ResponsePreparedness and Response

Models of system capabilities Models of system capabilities for mass casualty incidentsfor mass casualty incidentsPredictors of responsePredictors of responseLessons learned from prior Lessons learned from prior incidents to enhance resilienceincidents to enhance resilienceCollaboration with Israel Collaboration with Israel National Center for Trauma and National Center for Trauma and Emergency Medicine ResearchEmergency Medicine Research

0

1

2

3

4

5

6

7

23.50 23.54 23.58 0.02 0.06 0.10 0.14 0.18

time (O'clock)

numbe

r of

pat

ient

s

Critical (ISS 25+)Severe (ISS 16-24)Moderate (ISS 9-14)Minor (ISS 1-8)

Patient arrival by time and severity,level I trauma center

Patient arrival by time and severity,Patient arrival by time and severity,level I trauma centerlevel I trauma center

Israel National Center for Trauma and Emergency Medicine Research, Gertner InstituteIsrael National Center for Trauma and Emergency Medicine ResearcIsrael National Center for Trauma and Emergency Medicine Research, h, GertnerGertner InstituteInstitute

MAJOR GOALS

Short-Term: Define key elements in emergency medical response to pediatric mass trauma events utilizing data from Israeli experience. Current US practice is direct transport to hospitals for triage and treatment.

Long-Term: Determine applicability of mass trauma experience for bioterrorism mass casualty events in order to develop integrated model of pediatric mass casualty management strategies in the event of exposure to bacterial, viral, or toxin pathogens used by terrorists.

MAJOR GOALS MAJOR GOALS

ShortShort--Term: Define key elements in Term: Define key elements in emergency medical response to emergency medical response to pediatric mass trauma events utilizing pediatric mass trauma events utilizing data from Israeli experience. Current data from Israeli experience. Current US practice is direct transport to US practice is direct transport to hospitals for triage and treatment. hospitals for triage and treatment.

LongLong--Term: Determine applicability Term: Determine applicability of mass trauma experience for of mass trauma experience for bioterrorism mass casualty events in bioterrorism mass casualty events in order to develop integrated model of order to develop integrated model of pediatric mass casualty management pediatric mass casualty management strategies in the event of exposure to strategies in the event of exposure to bacterial, viral, or toxin pathogens bacterial, viral, or toxin pathogens used by terrorists. used by terrorists.

BEHAVIORAL DYNAMICSBEHAVIORAL DYNAMICSBEHAVIORAL DYNAMICS

Investigate Psychological Consequences

Emotional, Behavioral, and Cognitive Effects (distress responses, behavioral changes, and psychiatric illness)Predictors of ResponseRecovery EnvironmentResilience

Investigate Psychological Investigate Psychological ConsequencesConsequences

Emotional, Behavioral, and Emotional, Behavioral, and Cognitive Effects (dCognitive Effects (distress istress responses, behavioral changes, responses, behavioral changes, and psychiatric illness)and psychiatric illness)Predictors of ResponsePredictors of ResponseRecovery EnvironmentRecovery EnvironmentResilienceResilience

Distress Response

Psychiatric Illness

Behavior Change

Oklahoma City 1995 Bombing SurvivorsOklahoma City 1995 Bombing SurvivorsOklahoma City 1995 Bombing Survivors

45.1

34.3

22.5

6.69.4

05

101520253035404550

Anydisorder

PTSD Depression Panic AlcoholUse

% sample

North et al. 1999North et al. 1999

MAJOR GOALS

Key Challenge: Assess impact of behavioral dynamics on terrorist actions and response to terrorism

Short-Term: Apply attack-oriented analysis to identify which pathogens are of interest for bioterrorism. Identify emotional and behavioral issues specific to bioterrorism.

Long-Term: Develop models for incorporating prevention and intervention approaches to emotional and behavioral health. Evaluate behavioral dynamics of terrorism to enhance counter measures.

MAJOR GOALSMAJOR GOALS

Key Challenge: Assess impact of Key Challenge: Assess impact of behavioral dynamics on terrorist behavioral dynamics on terrorist actions and response to terrorismactions and response to terrorism

ShortShort--Term: Apply attackTerm: Apply attack--oriented oriented analysis to identify which pathogens analysis to identify which pathogens are of interest for bioterrorism. are of interest for bioterrorism. Identify emotional and behavioral Identify emotional and behavioral issues specific to bioterrorism. issues specific to bioterrorism.

LongLong--Term: Develop models for Term: Develop models for incorporating prevention and incorporating prevention and intervention approaches to emotional intervention approaches to emotional and behavioral health. Evaluate and behavioral health. Evaluate behavioral dynamics of terrorism to behavioral dynamics of terrorism to enhance counter measures. enhance counter measures.

INTERNATIONAL COLLABORATION: RUSSIAINTERNATIONAL COLLABORATION: RUSSIAINTERNATIONAL COLLABORATION: RUSSIA

Key Challenge: Developing effective research collaboration on projects with scientists in Russian bioresearch institutes to reduce the threat of bioterrorism and proliferation

Key Challenge: Developing effective research collaboration on projects with scientists in Russian bioresearch institutes to reduce the threat of bioterrorism and proliferation

Potential collaborative research areas:

AnthraxAvian FluTularemiaPneumonic PlagueAerosol BiologyAntivirals and Novel Therapeutics

Potential collaborative research areas:

AnthraxAvian FluTularemiaPneumonic PlagueAerosol BiologyAntivirals and Novel Therapeutics

Established Contacts:State Research Center for Virology and

Biotechnology "VEKTOR“ (Koltsovo)State Research Center for Applied Microbiology

(Obolensk) Institute of Immunological Engineering

(Lubuchany) Gamaleya Research Institute for Epidemiology

and Microbiology RAMS (Moscow)Institute of Computational Mathematics and

Mathematical Geophysics SB RAS (Novosibirsk)Institute of Atmospheric Optics SB RAS

(Tomsk)Institute of Chemical Biology and Fundamental

Medicine SB RAS (Novosibirsk)Shemyakin-Ovchinnikov Institute of Bioorganic

Chemistry RAS (Moscow)

Established Contacts:State Research Center for Virology and

Biotechnology "VEKTOR“ (Koltsovo)State Research Center for Applied Microbiology

(Obolensk) Institute of Immunological Engineering

(Lubuchany) Gamaleya Research Institute for Epidemiology

and Microbiology RAMS (Moscow)Institute of Computational Mathematics and

Mathematical Geophysics SB RAS (Novosibirsk)Institute of Atmospheric Optics SB RAS

(Tomsk)Institute of Chemical Biology and Fundamental

Medicine SB RAS (Novosibirsk)Shemyakin-Ovchinnikov Institute of Bioorganic

Chemistry RAS (Moscow)

Point-of-Contact PointPoint--ofof--Contact Contact

Dr. Larry RegensDr. Larry RegensDr. Larry Regens

Phone: 405-271-2070 ext 46770Fax: 405-271-1971E-mail: larry-regens@ouhsc.edu

Phone: 405Phone: 405--271271--2070 ext 467702070 ext 46770Fax:Fax: 405405--271271--19711971EE--mail: larrymail: larry--regens@ouhsc.eduregens@ouhsc.edu

Center for BiosecurityCollege of Public HealthUniversity of Oklahoma Health Sciences Center801 N.E. 13th StreetOklahoma City, OK 73104

Center for BiosecurityCenter for BiosecurityCollege of Public HealthCollege of Public HealthUniversity of Oklahoma Health University of Oklahoma Health Sciences CenterSciences Center801 N.E. 13th Street801 N.E. 13th StreetOklahoma City, OK 73104Oklahoma City, OK 73104

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