For the fiscal year 2010-2011 (FY10-FY11) period, JSTO-CBD released a solicitation for research proposals for chemical and biological defense. Research ranges from basic research (6.1 funding) to more mature applied research (6.2 funding) and advanced technology development (6.3 funding). It encompasses a broad spectrum of topics that address chemical and biological defense S&T requirements. Medical chemical and biological research topic areas included the following:

• Medical Basic Research: Provides the supporting sciences to expand basic knowledge in threat agent biology and chemistry to enable the development of lead candidate vaccines, treatments, and pharmaceuticals against chemical and biological threat agents. Biologically based basic research focuses on understanding biological warfare agents of interest and their pathways, virulence, immunization factors, and identification. Chemically based basic research focuses on understanding chemical warfare agents of interest and their mechanisms of action, toxicity, cellular mechanisms of injury, and identification.
• Biological Pretreatments: Dedicated to research and development of vaccines and technologies given to the service member prior to potential exposure to biological agents. The goal is to reduce or prevent entirely adverse effects of exposure.
• Biological Therapeutics: Dedicated to providing medical solutions for military requirements to sustain and protect the force in biological environments. Biological Therapeutics deals primarily with medical countermeasures to bacterial, viral, and toxin agent exposure.
• Biological Diagnostics: Dedicated to developing improved screening procedures and analytical methods to verify exposure and determine effects of exposure to biological warfare agents.
• Chemical Medical Countermeasures: Dedicated to developing medical countermeasures (i.e., pretreatments, therapeutics, and diagnostics) to protect the Warfighter against chemical warfare agents, both traditional and nontraditional.

For extramural organizations, including universities, industry, or other private institutions, the primary means for submitting research preproposals is through the DTRA Broad Agency Announcement. Chemical and biological defense S&T programs are managed by JSTO-CBD at DTRA.

DTRA solicits proposals for its requirements through the Federal Business Opportunities (FedBizOpps) and the DoD Small Business Innovation Research (SBIR) Program solicitations.

In addition to submitting proposals directly to DTRA, extramural partners may instead choose to partner with an intramural laboratory. There are a variety of mechanisms available for USAMRDC to work together with industry, including the following mechanisms:

• Cooperative Research and Development Agreements
• Material Transfer Agreements
• Patent License Agreements
• Clinical Trial Agreements
• Test and Evaluation Agreements
• Technical Assistance Agreements
• Partnership Intermediaries

The DTRA JSTO-CBD also invites U.S. Government laboratories to submit research proposals on chemical and biological defense, and proposals for these intramural efforts are managed on the Joint Chemical and Biological Defense Science and Technology Program web site at https://jacks.jpeocbrnd.army.mil/JETT/Register/384.

The DoD CBDP is the lead organization providing RDA of capabilities to protect the Warfighter. Other federal agencies are providing related capabilities, especially in the protection of civilians and emergency personnel. Other organizations conducting related research include:

• The Department of Health and Human Services, including the National Institute of Allergy and Infectious Diseases (NIAID), the Biomedical Advanced Research and Development Authority, and the Centers for Disease Control and Prevention (CDC).
• The Department of Homeland Security, especially the National Biodefense Analysis and Countermeasures Center.

The roles and responsibilities of the various federal agencies are outlined in Biodefense for the 21st Century (HSPD-10) and Medical Countermeasures Against Weapons of Mass Destruction (HSPD-18).

The CBDP RDA Plan details mid- and long-term CBDP goals, objectives, and transition of materiel within each phase of the acquisition process consistent with the Under Secretary of Defense for Acquisition, Technology, and Logistics' comprehensive RDA strategy in accordance with the National Military Strategy to Combat Weapons of Mass Destruction. To request a copy of the January 2009 DoD CBDP RDA Plan, contact the CBRN Defense Program Analysis and Integration Office RDA Manager at 410-436-5743 or the RDA Coordinator at 410-436-2080.

Medical S&T successes in FY07 included the establishment of assay standards and the focus on knowledge-based publications, which resulted in more than 150 peer-reviewed publications and 33 patents.

Other medical chemical and biological S&T program research accomplishments are outlined in the May 2008 DoD CBDP Annual Report to Congress and include the following:

Medical Biological Defense - Diagnostics:

• The U.S. Food and Drug Administration (FDA) cleared the Q-flow kit for DNA extraction from blood, and it is currently being fielded in the Joint Biological Agent Identification and Diagnostic System Block I deployment package. This kit addresses the main user-identified issues of the previous kit by eliminating the need for a large tabletop centrifuge and decreasing the sample volume required by approximately 1,000-fold.
• Established standards for reporting data on assay design, optimization, and performance. These also are being adopted for use by the environmental and infectious disease communities and have been presented to our international partners.

Medical Biological Defense - Therapeutics:

• Sponsored the establishment of a clinical field site for orthopoxvirus in the Democratic Republic of Congo.
  • Enrolls more than 100 patients with monkeypox annually; these patients are provided the current standard of care for this disease.
  • Collects human pathogenesis data, which are compared with similar data generated in current animal models.
  • Advanced clinical developers, NIAID, and SIGA Technologies will manage the site in the future.
• ST-246 (SIGA Technologies)-an oral antiviral therapeutic drug.
  • Demonstrated 100% protection against monkeypox and human smallpox virus in NHP trials and is the first drug to do so.
  • Developed an intravenous monkeypox animal model that is being used as the pivotal animal model in the FDA licensure process.
  • At the CDC's request, it was used recently to successfully treat a child having significant atopic dermatitis and a disseminated case of the disease acquired from contact with a parent's smallpox vaccination.

Medical Chemical Defense - Pretreatments:

• Recombinant BioScavenger pretreatment of guinea pigs followed by exposure to soman or VX resulted in 100% survival with no signs of toxicity or behavioral impairment.
• Developed and validated physiologically based pharmacokinetic/pharmacodynamic models for intravenous, subcutaneous, and inhalational administration of soman in three animal models.
• Further refined and analyzed the x-ray structure of candidate bioscavenger yCE.
• Cloned, sequenced, expressed, purified, and kinetically characterized more than eight mutants of yCE to increase organophosphorous acid anhydrase.
• Achieved up to a 20-fold increase in the specificity constant for carboxyl acid ester (pNPA) hydrolysis and at least a 200-fold increase in paraoxon reactivity through site-directed mutagenesis of candidate bioscavengers.
• Continued characterization of human serum paraoxonase 1 as a third-generation bioscavenger.

Medical Chemical Defense - Diagnostics:

• Completed development of a robotic, whole-blood diagnostic system for nerve agent exposure.
• Continued comparative research into field-sampling techniques and technologies for postexposure diagnosis.

Medical Chemical Defense - Therapeutics:

• Developed a mathematical molecular model to clarify the reactivation of inhibited AChE, as well as the effect of substituent groups on the reactivation event..
• Initiated research into technologies to enhance blood-brain barrier penetration for nerve agent countermeasures.
• Used site-directed mutagenesis to better identify the role of the key amino acids in the reactivation event.
• Used proteomic analysis to identify changes to proteome and genome of neuronal tissue following exposure to nerve agent.
• Evaluated effects of nerve agents on mitochondrial function and tested efficacy of cyclosporine A and its analogs at mitigating damage.
• Continued investigation of gross, cellular, and subcellular alterations of central nervous system tissue following exposure; identified temporal and spatial progression of damage in small animal models.
• Evaluated galantamine and huperzine A as potential replacements for pyridostigmine bromide.
• Testing putative compounds to ameliorate seizures and reduce lethality using established animal models; tested compounds included FDA-licensed drugs and proprietary compounds obtained through a Cooperative Research and Development Agreement.
• Identified and tested several potential compounds in small-animal seizure models for medical countermeasures for nontraditional agents.
• Investigated basic mode and mechanism of injury for nontraditional agents.

USAMRICD and USAMRIID have developed a number of training programs in chemical and biological defense, as follows.

• Field Identification of Biological Warfare Agents Course - This course was designed to allow students to set up, maintain, and operate a deployable laboratory under field conditions.
• Field Management of Chemical and Biological Casualties Course - This course focuses on emergency treatment, triage, decontamination, and evacuation of casualties.
• Hospital Management of Chemical, Biological, Radiological/Nuclear, and Explosive Incident Course - This course focuses on diagnosis, treatment, and incident management in response to mass casualty events of all types, including incidents involving weapons of mass destruction.
• Medical Management of Chemical and Biological Casualties Course - This course focuses on the pathophysiology, diagnosis, and treatment of chemical and biological casualties.
• Computer-Based Training - Computer modules offer service members a variety of interactive, multimedia learning courses both online and in compact disc format.