Hawaii Biotechnology Research: Interest Areas and Opportunities with the Department of Defense COL Karl Friedl, PhD Telemedicine & Advanced Technology Research Center US Army Medical Research & Materiel Command Frederick, MD

A hiatus exists between the inventor who knows what they could invent, if they only knew what was wanted, and the soldiers who know, or ought to know, what they want and would ask for it if they only knew how much science could do for them. - Winston S. Churchill (1929)

Agenda Military medical research interests Biomedical research in the DoD USAMRMC organizational structure Competitive funding opportunities Hawaii Federal Healthcare Network Program

Technology Shortfalls: Fill the Gaps Current Operational Concepts and Environment Future Operational Concepts and Environment Desired Capabilities S&T Shortfalls Needed S&T Work Needed S&T Work Capability Challenges Capability Needs Existing Tech or Non-Technology Solutions Ongoing S&T Work Existing Tech or Non-Technology Solutions Capability Today Capability Today

The Linear Approach to R&D Army Medical Product Development Life Cycle Fed / DoD Needs ICD ICD CDD CPD Opportunities, Gaps, & Resources MDD A B Program Management Initiation C Life Cycle Funding 6.1 6.2 6.3 6.4 6.5 6.7 Ops & Maint $ Research, Development, Test, & Evaluation (RDT&E) $ Procurement $ DoD Funding Categories 6.1 – 6.3: Basic research, applied research, and advanced technology development 6.4 – 6.5: Program management activities 6.6: Program support including test and evaluation facilities 6.7: Improvements to existing operational systems Vannevar Bush model Basic research is a pacemaker of technological innovation but must be segregated to avoid premature thoughts of practical use Joint Capability Integration & Development System Documents ICD: Integrated Capabilities Documents CDD: Capability Development Documents CPD: Capability Production Documents

DoD Problem-solving Focus: Use-inspired Medical Research Understanding underlying science creates rule base to help solve future problems Low Emphasis on Fundamental Understanding High Emphasis on Basic Science Low Emphasis on Applications Pure basic research (Bohr) High Emphasis on Applications Pure applied research (Edison) Use-inspired basic research (Pasteur) Revolutionary Evolutionary

What are the DoD Medical Research Priorities. (Where do they come from National strategic plans (e.g., Quadrennial Review – in progress!) Secretary of Defense & other authoritative sources in the DoD and Services Armed Services Biomedical Research Evaluation and Management Near-term problems identified by field commanders & COCOMs

Secretary Gates' Press Briefing May 3, 2007 Apart from the war, this department and I have no higher priority than to ensure wounded servicemembers have the best care and facilities and ample assistance navigating the next step in their lives. That is what we intend to give them.

Current Priorities: Secretary Gates' Budget Briefing April 6, 2009 Recognize the critical and permanent nature of wounded, ill and injured, traumatic brain injury, and psychological health programs. This means institutionalizing and properly funding these efforts in the base budget and increasing overall spending by $300 million. The department will spend over $47 billion on healthcare in FY10.

Enduring Challenges: Old Medical Threats, New Science LIMB LOSS SHELL SHOCK HEMORRHAGE

Core Medical R&T Responds to Threats to Soldier Health and Performance Endemic Disease Threats Parasitic Diseases Bacterial Diseases Viral Diseases Operational Stressors Sleep Deprivation Traumatic Stress and Situational Stressors Physical Work Load Cognitive Burden & Operational Complexity Chemical/Biological Warfare Threats Bacterial Threats Viral Threats Toxin Threats Nerve Agents Vesicant Agents Blood Agents Combat Injuries Hemorrhage Head Trauma Blast Injury Systems Hazards Laser Blast Biomechanical Insults and Stresses Noise Environmental Hazards Heat and Cold Altitude Toxic Industrial Chemicals & Materials Inadequate Medical C4ISR

Pharmaceutical Advanced Development Pipeline at USAMMDA Pre-Clinical Phase 1 Phase 2 Phase 3 Licensed VACCINES Adenovirus Type 4 & 7 HIV Prime-Boost Dengue Tetravalent (Proof-of-Concept) (Proof-of-Concept Completed) (License Submitted) Leish Drug, PentostamTM Antimalarial-IV Artesunate Topical Leishmania Drug Antimalarial-Tafenoquine Leish Rapid Diagnostic ANTIPARASITIC DRUGS/Dx Intranasal Ketamine RBCs Extended Life Cryopreserved Platelets Freeze-Dried Plasma COMBAT CASUALTY CARE

Joint Force Health Protection Capability Gap Medical R&D OVERARCHING NEEDS: Maintain a Healthy & Fit Force Protect Personnel in the Field Diagnosis for Early Treatment Rapid Return to Duty Military Infectious Diseases Research Program Vaccines Prophylaxis/treatment drugs Diagnostics/prognostics Vector control HIV countermeasures (Congressional mandate) Combat Casualty Care Research Program Meet Demands on First Responders Reduce the Number of Deaths on the Battlefield Limit Brain Damage Improve Medic, Provider, and Team Training Restore Full Function Improve En Route Care Reduce Morbidity and “Died of Wounds” Rate Clinical Trials Military Operational Research Program Prevent, Detect and Treat Mental Health Problems and mTBI (Concussion) Prevent/Mitigate Blast, Blunt, Ballistic, and Impact Injury Reduce Attrition in Basic Combat Training Due to Injury and Mental Health Problems Prevent/Mitigate Injury from Environmental Exposures to Heat/Cold/Altitude and Toxic Chemicals and Materials Sustain Soldier Performance Medical Biological Defense Research Program Vaccines and pre-treatments Small molecule therapeutics Next generation diagnostics Animal model development Broad-spectrum therapeutics Medical Chemical Defense Research Program Nerve agent pre-treatments Therapeutics for nerve agents Therapeutics for vesicant injury Diagnostic assays/technologies Clinical and Regenerative Medicine Research Program Improve Prosthetic Function Enhance Self Regenerative Capacity Improve Limb/Organ Transplant Success Create Fully-Functioning Limbs/Organs Blast Injury Program Coordinating Office Develop Medical Standards for Individual and Combat Vehicle Crew Blast Protection Systems Elucidate the Mechanism of Blast-Induced Brain Injury Improve Diagnosis of mTBI Effectively Communicate Blast-Related Research Across the DoD Reset Advance Treatment Options 13 13

Key Blast Injury Research Topics (FY07-10 Investments) Injury Prevention ($183M) Blast Loading CFD Simulation Observed Pathology FEM Simulation Test Conditions Existence and mechanism of non-impact, blast- induced mTBI? Drugs to prevent and treat blast-related hearing loss Analysis of combat injuries and PPE performance (JTAPIC) Multi-effect blast injury models to improve protective equipment Resilience enhancement and prevention of PTSD R x Hair Cell Antioxidant Defenses Tissue engineering and prosthetics Return-to-duty Standards Recovery of function Reset ($141M) Before After Diagnostics and neuroprotectant drugs for TBI Hemorrhage control & blood products Treatment of psychological trauma Damage control orthopedics Pain management Acute Treatment ($437M)

DoD Blast Injury Research Extends Back to World War II Nuclear & conventional explosions Los Alamos & Albuquerque Cave blasts Armored Med Res Lab

New Science and Technology Options: Modernization of Military Medical R&D “Laying the tracks for the train” Prevention (Mitigate Risk) Acute Treatment (Mitigate Injury) Reset (Mitigate Disability) Personalized Medicine Diagnostics Regenerative Medicine Individual Resilience Provider Training Individual Retraining Biomedical Standards Wound Care Advanced Prosthetics Injury Surveillance Optimized Interventions Return-to-Duty Standards Systems Biology Methods Advanced Training Technologies & Neuroplasticity Computational Bioengineering, Biomaterials & Nanotechnologies Electronic Health Record Outcomes Research

Chemical Biological Defense Program Threat Focus Advanced Threats pathogens engineered to increase resistance, transmissibility, and virulence Traditional Threats intracellular bacterial pathogens (e.g., plague) viral hemorrhagic fevers (e.g., ebola) Enhanced Threats “bioprospecting” of virulent strains in nature cultivating virulent strains in the laboratory Emerging Threats natural diseases (e.g., pandemic flu, malaria) multidrug and vaccine resistant pathogens

www.tmti-cbdefense.org; ww.fedbizops.gov Chemical Biological Defense Program: Transformational Medical Technologies Initiative Develop broad-spectrum countermeasures and novel technology platforms (one drug, many bugs) Pursue countermeasures targeting common disease pathways or enhance the host’s immune system Integrate best efforts within government, academia, DoD, biotech industry, and small and large pharmaceutical corporations Provide seamless “end-to-end” product development Eliminate capability gaps by adding promising candidate technologies to the pipeline www.tmti-cbdefense.org; ww.fedbizops.gov

The Changing Operational Environment “Low level Persistent Conflict” General Casey, 14 Aug 07

& International Health The Changing Operational Environment “Low level Persistent Conflict” General Casey, 14 Aug 07 Stability Operations & International Health

Medical Research and Related Programs in the DoD DARPA (e.g., DSO) CBDP/DTRA (e.g., TMTI) SOCOM (BISC) VA-DoD sharing (e.g., JIF) NIH joint efforts Other Agencies DCoE for PH and TBI DCoE for Vision USAMRMC ARO NMRC ONR AFMOA AFRL AFOSR Services

Medical Research and Related Programs in the DoD DARPA (e.g., DSO) CBDP/DTRA (e.g., TMTI) SOCOM (BISC) VA-DoD sharing (e.g., JIF) NIH joint efforts Other Agencies DCoE for PH and TBI DCoE for Vision USAMRMC ARO NMRC ONR AFMOA AFRL AFOSR Services ASBREM

Armed Services Biomedical Research Evaluation & Management The ASBREM Committee shall: Review medical RDT&E program plans and accomplishments for quality, relevance, and responsiveness to military operational needs, the needs of the Military Health System, and the goals of Force Health Protection Review program plans and budgets in support of the various guidance documents relevant to National Security and to the missions and functions of the Department of Defense Provide coordination, recommendations, and support to DoD Executive Agencies and other DoD officials as requested, directed, or otherwise appropriate

Medical Research and Related Programs in the DoD ASBREM Joint Technical Coordinating Groups 1 Med Training Systems & Information Tech 2 Military Infectious Diseases 3 Chemical Defense 4 Biological Defense 5 Military Operational Medicine 6 Combat Casualty Care 7 Radiation Effects 8 Clinical and Rehabilitative Medicine

Defense Health Program: GDF Enhancement MISSION DESCRIPTION AND BUDGET ITEM JUSTIFICATION: This Program Element (PE) funds Advanced Component Development of medical products that are regulated by the U.S. Food and Drug Administration (FDA) and the accelerated transition of FDA licensed and unregulated products and medical practice guidelines to the military operational user through clinical and field validation studies. Projects in this PE are designed to address areas of interest to the Secretary of Defense and to close medical capability gaps associated with the Joint Force Health Protection Concept of Operations (JFHP CONOPS) and are complementary to research conducted by the Army, Navy and Air Force in analogous PEs. Projects include Trials for Accelerated Transition of Modeling and Simulation Technology for Medical Training/Education/Treatment; Trials for Accelerated Transition of Medical Technology, Practice Guidelines and Standards; Medical Products – Advanced Component Development; and Medical Information Technology Development. $198 M

Congressional Special Interest (CSI) RDA Programs About 50% of USAMRMC Funding Each Year Is Congressionally Directed Function of Congressional Special Interest (CSI) Research: Sponsor good science using Congressional appropriations that are not in the President’s budget Responsive to the intent of Congress, managed to maximize military relevance Process: Proposals peer reviewed for scientific merit prior to award Programs executed by extramural awardees and USAMRMC laboratories and acquisition offices Program Managers: USAMRMC Research Area Directorates (33%) U.S. Army Medical Materiel Development Activity (USAMMDA – 9%) Congressionally Directed Medical Research Programs Telemedicine and Advanced Technology Research Center TATRC 29% CDMRP 32% Core R&T 33% Advanced Development 9% Core Effort 39%

Medical Advanced Development Supporting Commands USAMMDA U.S. Army Medical Materiel Development Activity USAMMA U.S. Army Medical Materiel Agency Defense Medical Logistics Center Pharmaceutical Systems Applied Medical Systems Integrated Clinical Systems Medical Devices

Core Medical R&T Supporting Laboratories USAARL U.S. Army Aeromedical Research Laboratory USAISR U.S. Army Institute of Surgical Research USARIEM U.S. Army Research Institute of Environmental Medicine Combat Casualty Care 18.3% Military Operational Medicine 17.1% Infectious Diseases 23.6% Medical Biological Defense 25.5% Chemical 15.5% USAMRIID U.S. Army Medical Research Institute of Infectious Diseases USAMRICD U.S. Army Medical Research Institute of Chemical Defense WRAIR Walter Reed Army Institute of Research U.S. Army Medical Research Unit - Nairobi, Kenya Armed Forces Res Inst of Med Sci, Bangkok, Thailand US Army Medical Research Unit, Heidelberg, Germany US Army Dental and Trauma Research Detachment US Army Medical Research Detachment US Army Center for Env Health Med

FY09 Funding Opportunities: http://cdmrp.army.mil/ FY09 Funding Opportunities:

http://cdmrp.army.mil/

Medical Research and Related Funding Programs in the DoD DARPA (e.g., DSO) CBDP/DTRA (e.g., TMTI) SOCOM (BISC) VA-DoD sharing (e.g., JIF) NIH joint efforts Other Agencies DCoE for PH and TBI DCoE for Vision USAMRMC ARO NMRC ONR AFMOA AFRL AFOSR Services Small Business Innovative Research Small Business Technology Transfer (SBIR/STTR) http://www.acq.osd.mil/osbp/sbir/

KEY TATRC Initiatives and Portfolios Robotic rescue & evacuation Shelf stable diagnostics & vaccines Blood products & blood safety Natural orifice transluminal endoscopic surgery Advanced medical imaging Distance medical training & simulation Operating room of the future Prosthetics and human performance Regenerative medicine & biomaterials Virtual environments Computational models & tools Human/soldier phenome Performance & injury prediction models Cell phone-based systems Remote biomonitoring Global Biosurveillance Health information portal unified EHR Research data cube/ medical outcomes Pharmacovigilance e-HEALTH MEDICINE IN AUSTERE ENVIRONMENTS DIGITAL WARRIOR INTEGRATIVE MEDICINE HOSPITAL OF THE FUTURE Optimal healing environments Advanced pain management Complementary and alternative medicine Neuroplasticity/resilience Genomics/personalized medicine www.tatrc.org

TATRC Portfolios Joint Technical Coordinating Group 1. Medical Information & Training Technologies 4. Infectious Diseases 5. Military Operational Medicine 6. Combat Casualty Care 8. Clinical & Rehabilitative Medicine Psych Health Dr. Shore Resilience & Retraining MAJ Brininger Simulation & Training Technology Mr. Wiehagen Bio-Monitoring Technologies Dr. Lai Medical Robotics Dr. Gilbert Advanced Prosthetics Mr. Turner Human Performance Optimization Dr. Cardin Medical Imaging Technologies Dr. Pacifico Health Information Technologies LCDR Steffensen Computational Biology Dr. Reifman Genomics / Proteomics Ms. Stanley International Health Ms. Barrigan Nano-Medicine & Biomaterials Dr. Grundfest Regenerative Medicine Dr. Lai Infectious Disease Dr. Carney Medical Logistics Mr. DePasquale Blood Products & Safety Mr. Malloy Head & Spinal Cord Injury Dr. Curley Vision Mr. Read Trauma Dr. Broderick Acoustic Trauma Dr. Holtel Slide 33 of 12

Hawaii Federal Health Care Network (AKAMAI II) – FY10 Competitive RFP AKAMAI II supports applied research, development and deployment of telehealth and healthcare technology, biotechnology, clinical informatics, VA/DoD systems interoperability, to improve access and the quality of care to service members, their families, and impacted communities. With a focus on programs that align closely with military medical requirements, a competitive process will be used to provide funding in Hawaii to develop advanced medical technologies and biotechnology research critical to our nation's military medicine and the warfighter. Priority will be given to innovative collaborations between Hawaii-based industries and the Department of Defense. Outside partnerships that help to bring unique expertise to research in Hawaii to solve military medical problems will also be an important factor. http://inouye.senate.gov/Congressional_Initiatives/

Basic Steps to Innovation in the Hawaii Federal Health Care Network Come up with a concept that would be immensely important to the DoD, if successful Secure the intellectual property Publish the seminal supporting article in peer reviewed literature Conduct the initial risk mitigation studies (e.g., toxicity) that will encourage investors

Hawaii Biomedical Research Advantages and Dual Use Applications for DoD Stable population (~1.2M) Unique healthcare system and DoD-VA sharing of facilities (great starting point to optimize practices) Distributed across islands (e.g., model of remote health care access) Chronic health care concerns, even though a state with the best longevity (e.g., preventive medicine interventions and personalized health care/personal empowerment opportunities) Modest size makes manageable testbed and model system and increases cooperation in the islands

AAMTI: Pediatric Telecardiology Referrals with Echocardiographic Validation Pacific Rim Pediatric Heartsounds Trial: Store and Forward telcardiology with echocardiographic validation Simultaneous Multi-site Phonocardiography: A simplified heartsound Improved heartsound signal analysis using simultaneous multi-site phonocardiograms in children Pediatric Multi-site Phonocardiography: Automated interpretation of pediatric heartsounds Telecardiology evaluation of newborns with heart murmurs using simultaneous, multi-site phonocardiography AMEDD Advanced Medical Technology Initiative

Janus – DoD and VA Common Data View

Pacific Asynchronous Tele-Health (PATH) Teleconsultation Telehealth Services -VA Pacific Islands Health Care System (VAPICS)

Telehealth Voice Therapy in Remote Regions in the Pacific Basin ICU Multipoint Military Pacific Consultation Using Telehealth (IMMPACT) Telehealth Voice Therapy in Remote Regions in the Pacific Basin

Environmental Medical Surveillance (CBI “wet ware” / “canary”) Cell Matrix Chips for Air/Water Monitoring of Toxic Chemicals Principal Investigator: Kevin Chinn, PhD; Cellular Bioengineering, Inc.

Cell-based Treatments Treatment of Peripheral Vascular Disease by Adipose Derived Stromal Cell Injection Principal Investigator: Paul Kosnik PhD; Tissue Genesis, INC. Development of Technologies for Bioengineered Tissue Repair Principal Investigator: Mark Mugiishi, MD; Cellular Bioengineering, Inc.

Nanotechnology Capabilities RAIDER: Rapid Adverse Identifier for Drugs and Evaluation Resource Principal Investigator: Joanne S.M. Ebesu, Ph.D.; Oceanit SEM image of nanoarray functionalized with antibodies

Development of the versaHSDI system – Colon Automated disease detection Video reconstructed colon model Local 3D rendering 3-D rendering software development to enable and develop Computer Aided Diagnosis and in situ pathology for colon cancer detection

Neurophysiologically-based Performance Monitoring and Enhancement Devices Intelligent PTSD Classification and Treatment-Augmentation Technology The device will utilize off the shelf technology and Archinoetics developed hardware to produce an integrated, unobtrusive monitoring/communication capability. Warfighter Physiologic System Interface Research

Broadband Respiratory Virus Surveillance

SimCenter Hawaii Technology Enabled Learning and Intervention Systems Virtual Reality Applications for Health Care Education and Training

TATRC Science & Engineering Research Support Dr. Stan Saiki, Chief, TATRC Hui Dr. Chuck Peterson, Chief Scientist Ms. Jessica Kenyon, Chief, TATRC West Mr. Ron Marchessault, ORTA www.tatrc.org