U.S. military medical researchers have focused on how to defend against the threat of biological and chemical warfare since World War I. With recent conflicts and terrorist attacks, the threat of bioterrorism has quickly risen to the consciousness of the general public. The threatened deliberate use of biological agents as weapons in the future may require infectious diseases to be classified as battlefield related and will be extremely serious to the unprepared.
Since 1991, the Biological Defense Research Directorate (BDRD) at NMRC researched ways to protect military personnel in the event of a biological attack. They became the leader in the field of detection, including hand-held assays, molecular diagnostics, and confirmatory analysis. Following the Base Realignment and Closure (BRAC) commission of 2005 all government Biodefense assets were realigned at Fort Detrick. This coincided with the movement in 2011 of NMRC biodefense assets, including BDRD, into a new building that became Naval Medical Research Center – Frederick (NMRC-F).
National Testing and Analysis
BDRD serves as a national resource providing testing and analysis for the presence of anthrax and other potential biological hazards. Its portable laboratory, the only one of its kind devoted to detecting biological agents, was deployed to conduct tests at the Pentagon following the crash of American Airlines flight 77 on 11 September 2001 and deployed to New York City to assist with bio-detection.
After the subsequent anthrax attacks in October 2001, BDRD analyzed more than 16,000 samples from the Capitol. They detected the presence of anthrax at Hart Senate Office Building, the Supreme Court, and several area mail processing facilities. The laboratory has been present at multiple high profile events including the 2002 Salt Lake City Winter Olympics rendering its testing services. In 2014 during the Ebola outbreak crisis in Western Africa, BDRD responded by mobilizing the laboratories to Liberia in response to Operation United Assistance. In 2015 during the DoD response to the US Army Dugway Proving Ground inadvertent shipping of live B. anthracis spores as reported by USA Today, BDRD was a key contributor to the Biological Safety Task Force, engaging to help provide for a safer and more secure system in handling Biological Select Agents and Toxins.
Genomics and Bioinformatics
This department is responsible for Sequencing, Bioinformatics, Software development and Phage applications. Recent applications that have arisen from this department include:
EDGE Bioinformatic Software which is a DTRA funded collaborative effort with LANL and is a design & testing of field-forward bioinformatic software.
AssembleIt!, a DTRA funded game development crowd-sourcing genome assembly game.
A completed study of genome variation in 55 Bacillus anthracis strains using an Affymetrix resequencing microarray, and determined that the Bacillus cereus strain G9241, which causes an anthrax-like disease.
Targeted Sequencing for increased sensitivity, viral detection & surveillance (ILIR funded; collaboration w/ Illumina) and Detection of antibiotic resistance genes (Collaboration w/ LLNL).
This department also has embarked into Phage Therapeutics which has started a congressionally funded collaborative effort with Wounds Department therapeutics for difficult to treat infections.
BDRD pioneered the development of small hand-held assays that identify most of the common biological threats, including anthrax. The Department of Defense (DoD), Federal Bureau of Investigation, and the Secret Service routinely use these assays, which identify the biological agent within 15 minutes.
These assays were selected by the Joint Program Office for Biological Defense as the standard assay produced for the DoD. They provide rapid diagnostics and detection assays for field identification of biothreat agents Develop biosensor-linked automated detection systems with real-time capability. Produce antibodies for the detection of new and emerging disease threats. They are an ISO Guide 34 Accredited Certified Reference Material Producer (Antibodies) and operate a CDC-Registered Toxin Lab and CDC-Registered BSL3 Lab (Operated with Ops Dept.)
They are responsible for transition rapid detection assays to operational forces. Recent accomplishments include:
Licensed anti-Ebola polyclonal antibody to Orasure for large-scale assay production at request of CDC (annual royalty agreement)
Ongoing participation by Department Head in BSAT-related working groups as co-PI of BDRD/NMRC BSL3 and BSL2 BSAT labs
New project to test and evaluate platform for Common Analytical Laboratory System (CALS)
Scientists at NMRC developed a real-time Polymerase Chain Reaction (PCR) based diagnostics for confirmatory testing. ISO Guide 34/17025 Accredited Certified Reference Material Producer (Real Time PCR reagents), these confirmatory assays are based on the DNA sequence of a particular biological agent. BDRD's anthrax assays are the standard assays for the Centers for Disease Control and Prevention. The final step in the confirmation process, definitive testing, can then be done at the NMRC laboratories in their Bio-Safety Level 3 facility.Recent accomplishments include:
• Produced ~500,000 Ebola surveillance assays in support of ongoing USG response in Western Africa
• Produced ~200,000 Ebola EUA kits for testing of US personnel by DoD MTFs (CONUS and OCONUS) and CDC LRN network (63 public health labs)
The first portable laboratory capable of conducting molecular detection was developed by the BDRD in 1991. This unique laboratory allows military personnel in the field to quickly conduct confirmatory assays to determine whether biological agents are present. It was deployed in Desert Storm/Desert Shield, and similar capabilities were deployed in Operation Iraqi Freedom. The portable lab currently weighs approximately 1,000 pounds and requires three people to run it. It can be checked onto commercial airlines and requires only gas and motor oil to operate. The portable laboratory holds supplies sufficient to process about 150 samples with PCR and ELISA testing. It also includes protective gear for the personnel, a generator, a freezer, field lighting, and field uninterruptible power supply (UPS).
OPS is responsible for:
• Provide material research and development support through the operation of the BSL-3 laboratory.
• Provide specialty analysis of samples for the presence and identification of biological threats.
• Develop a rapidly deployable bio-threat agent identification laboratory incorporating immunological, molecular, and microbiological identification techniques.
• Continued requests to provide BW agent overview and detection training to Special Operations assets
• JBAIDS QA/PT 23 ships/USAF 51 Sites/NEPMUs 3 sites) ~582 specimens/yr, pre-deployment ship visits, 24/7 Reach-back support to Fleet
• Transitioning to NGDS in FY16/17 – include Army
Recent accomplishments Include:
• CDC inspections, Anthrax Mishap investigation and GAO engagement
• Plague confirmation testing for JSTO/DTRA 24-M Challenge
• Joint/Allied FTX refining BW TTPs and CONOPs
Navy Ebola Detection Labs – Liberia – which was a major proof of concept for the continued exercise of these mobile laboratories. BDRD mobile labs processed thousands of samples, turning a diagnosis of Ebola from days to mere hours, a major improvement to health increasing the chances for potential Ebola victims.
International Field Microbiology
The institute for Functional Medicine provides Subject Matter Expertise to the Defense Threat Reduction Agency, focusing primarily on international laboratory training efforts and outbreak response.
Recent accomplishments include:
• Diagnostic efforts and training on Ebola in Liberia
• Authored Ebola Diagnostic Training manual to be used in the Liberian national curriculum.
• Aided the pre-deployment training of Navy personnel prior to Liberia mission
• Lumpy Skin Disease (LSDV) outbreak in Iraq, Azerbaijan and Georgia
• Dengue outbreak in Tanzania
• ISO-certified media production facility at KEMRI
• PCR training in Azerbaijan and Armenia
• Provided assays with synthetic positive controls to NAMRU 2, 3, and 6 (MERS-CoV, Influenza, Yellow Fever, Hantavirus, Norovirus, etc.)
One of the major programs in Clinical Research is:
ACESO (Austere environment Consortium for Enhanced Sepsis Outcomes)
Sepsis is a complication caused by the body’s overwhelming and life-threatening response to an infection, which can lead to tissue damage, organ failure, and death.
ACESO is an international collaboration of experts focusing on research to facilitate early recognition, improved treatment, and full recovery for severe infection in forward-deployed and resource-constrained settings.
• Observational studies of sepsis host biomarkers
• >450 patients enrolled between Cambodia, Duke, Ghana
• Discovery for classifiers of disease and prognosis
• Clinical trial for sepsis CPG’s in resource-limited settings
• Fort Portal, Uganda
As a result of the lessons learned from the 2014-15 Ebola epidemic in West Africa, and using funds left over from Operation United Assistance, the DoD launched the Joint West Africa Research Group in late 2015. Co-led by the Naval Medical Research Center's Austere environment Consortium for Enhanced Sepsis Outcomes (ACESO), Naval Medical Research Unit #3's Ghana Detachment, and the Walter Reed Army Institute of Research's Military HIV Research Program, JWARG built on existing research partnerships in Liberia, Ghana, and Nigeria to address 3 goals: 1) Prevent repeat emerging infectious disease surprise in West Africa; 2) Advance DoD medical research mission for countermeasures to infectious diseases threats; 3) Build sustainable partnerships and platforms to address DoD research needs and host-nation public health threats.