DARPA has proposed 2012 budget which includes a review of projects and what was achieved in 2010 and what is being done in 2011 and what is planned for 2012 (380 pages). Budget is about $3 billion per year. Here I look at a selection of projects that are medical related.
Human Assisted Neural Devices – The aim of this project is to develop devices to restore memory by bridging gaps in injured brains, so that wounded soldiers can be returned to active duty quickly with improved performance on the battlefield. DARPA says this research will significantly advance models of how the human brain works in terms of short-term memory encoding, neural computation and reorganization. The 2012 estimate is $14.9 million and $34.2 million was allocated for the two years prior.
– Assess ability of primate to retain short-term memory encoding following simulated injury through use of neural codes.
– Identify homogeneity of neural codes involving long-term memory between primates conducting similar long-term memory tasks.
– Map dynamic functional motor and sensory networks and develop methods for characterizing brain-wide sensory/motor tasks.
– Determine the role of specific neural pathways in a complex motor/sensory task through perturbation of existing and defined
functional networks in primate and rodent experiments.
– Investigate stimulation of sensory networks to determine how sensory information is encoded and utilized by the brain.
– Improve learning and performance of primates during complex sensorimotor tasks through robust decoding of neural activity.
– Develop models of neural behavior that more accurately approximate biological signaling.
– Fabricate neural interfaces capable of stimulating and recording multiple channels of neural activity at distributed sites throughout the brain.
Tactical Biomedical Technologies – More than half of the fatalities on the battlefield are due to hemorrhage. This initiative will enable nonmedical personnel to diagnose and treat injuries, including locating and stopping deep bleeders in the thorax or abdomen. Researchers are also working to develop new pain control treatments that can be administered in medically unmonitored sites like the battlefield. The budget estimate for 2012 is $17 million.
Blood Pharming – The objective is to produce a large quantity of safe, transfusable blood, satisfying a large battlefield demand and reducing the logistics of sourcing donated blood. Biotech firm Arteriocyte worked with researchers at Johns Hopkins University to develop the NANEX Stem Cell Expansion technology, which allows for quick reproduction of universal donor red blood units from umbilical cord blood. The technology shows promise in the lab, but requires further development to produce a large supply of red blood cells at an effective cost. DARPA has earmarked $4.3 million for the blood pharming project in 2012, further to the $17 million total allocated in 2010-2011.
Virtual Tricorder Program project involves developing a technology to analyze data collected on individual patients to visualize and assess their health status. Data would then be compared to electronic medical records. By running simulations, the tricorder could help physicians predict how pharmaceuticals would affect the patient. No specific funds are budgeted for 2012, but conceptual work will begin to develop techniques for combining medical imagery and modeling the physiological impact of medications.
Preventing Violent Explosive Neurologic Trauma (PREVENT) – Medical ($7.7 million over FY 2010 and FY2011) PREVENT is funded in the newly created
Budget Activity 6.1 Medical Program Element 0601117E, beginning in FY 2012.
Develop and design devices and diagnostic platforms suitable for blastbrain injury detection in theater capable of early identification of blast neurotrauma from physiological, neurological, and behavioral changes.
Biological Adaptation, Assembly and Manufacturing ($25.5 million from 2010-2012)
The Biological Adaptation, Assembly and Manufacturing program will examine the structure, function, and informational basis underlying biological system adaptation, and the factors employed by the organism to assemble and manufacture complex biological subsystems. The unique stability afforded biological systems in their ability to adapt to wide extremes of physical and endurance (e.g., heat, cold, and sleeplessness) parameters will be examined and exploited in order to engineer stability into biological systems required for the military (such as blood, bioengineered tissues or other therapeutics). In addition, the fault tolerance present in biological systems will be exploited in order to assemble and manufacture complex physical and multi-functional systems, both biological and abiotic (such as tissue constructs designed for reconstructive surgery). These systems include novel load-bearing bio-interactive materials and composites for repair of severe hard tissue trauma, including complex bone fractures. A key new antibody technology will develop the ideal antibody master molecule for use in unattended sensors that maintains high temperature stability and controllable affinity for threat agents. Using the Freytag triangle structure, the interplay of narratives or stories may reveal how they tap into an array of mechanisms implicated in memory, reasoning, and strategy behavior. Applications to Defense systems include the development of chemical and biological sensors, tools for strategic military decision-makers involved in public relations and information operations, and improved warfighter battlefield survivability.
FY 2010 Accomplishments:
– Developed novel resorbable wet adhesives with the mechanical properties of natural bone, for inclusion into fracture putty formulation.
– Demonstrated fracture putty in small animal model of bone fracture.
– Initiated large animal studies of fracture putty for bone fracture repair.
– Identified fundamental mechanisms for controlling antibody stability and affinity.
– Initiated efforts to modify antibody affinity and temperature stability of the MS2 scFv antibody.
– Determined the baseline binding parameters of the anti-MS2 scFv and established the methodology for evaluating improvements in antibody performance.
FY 2011 Plans:
– Demonstrate fracture putty in large animal model of bone fracture, with independent validation.
– Initiate expanded large animal studies of fracture putty in preparation for human clinical trials.
– Demonstrate the ability to produce an antibody with thermal stability from room temperature up to 60 degrees Celsius.
– Combine identified antibody stability and affinity capabilities into a single “Master Antibody Molecule” that exhibits two target metrics against a single biological threat agent and deliver a minimum of two grams for testing by a government laboratory.
– Incorporate the identified “Master Antibody Molecule” into an existing biosensor platform and demonstrate advanced capability in terms of robustness and potential for multiplexing.
– Initiate investigations into the relationship between dopaminergic-driven learning systems, hormones/neurotransmitters such as oxytocin, emotion-cognition interactions, and narrative structures.
FY 2012 Plans:
– Further investigate use of fracture putty in fixation and healing of large animal injury.
– Revise design of fracture putty compounds as appropriate for safety in human clinical trials.
– Explore and refine foundational assumptions on the utility of the Freytag structure (“setup-climax-resolution”) for narrative
analysis, including determining relationships between decomposed stories and neuropsychological mechanisms, and understanding relationships between narratives and behavior.
– Develop decomposition frameworks and initial cluster of neurobiological mechanisms to better understand their relationship.
– Develop tools to link analytic frameworks, neural mechanisms, and environmental variables to a particular story.
Dialysis-Like Therapeutics $5 million in 2012
Description: Sepsis, a bacterial infection of the blood stream, is a significant cause of injury and death among combat-injured soldiers. The key goal of this program is to run the blood volume (approximately five liters) through an external machine (akin to a dialysis system) and literally scrub out harmful bacteria and their toxins. The proposed approach is low-shear/low-resistance fluidic structures to connect cellular and biomolecular purification techniques for blood purification.
Initial basic research will develop novel low-shear, low-resistance fluidic structures that enable rapid, large volume blood filtration. Additional research will develop novel intrinsic separation techniques that selectively remove bacteria, toxins and host cells from complex fluids, as well as new methods for continuous sensing of these components. Finally, research into predictive control techniques for directing patient health will close the sense, scrub, and control loop. The applied research portion of the program is budgeted in PE 0602115E, Project BT-01.
FY 2012 Plans:
– Develop “label-free” intrinsic separation technologies that remove pathogens of different classes, toxins, and activated cells from complex fluids.
– Design high flow, low shear microfluidics to transport wound fluid and blood without cellular activation.
– Design pathogen sensors for continuous use in complex biological fluids.
– Establish mathematical models to classify and predict patient state over relevant time scales.
Unconventional Therapeutics* ($9 million in 2012)
Description: * Previously funded in PE 0602383E, Project BW-01
This thrust is developing unique and unconventional approaches to ensure that soldiers are protected against a wide variety of naturally occurring, indigenous or engineered threats. This program will develop approaches to counter any natural or anthropogenic pathogen within one week. This includes development of countermeasures that do not require prior knowledge of the pathogen and are broadly applicable to multiple unrelated bacterial and/or viral infectious agents. The integration of academic research programs with pharmaceutical development efforts will result in reducing the traditional drug development cycle timeframe.
FY 2012 Plans:
– Demonstrate various technologies that can increase the median infectious dose (ID50) of a given pathogen by 100-fold in an animal model compared to the untreated control ID50 in order to prevent infection.
– Demonstrate a 4-fold increase in survival time after a lethal dose (LD95) challenge of a given pathogen in an animal model due to administered technology.
– Demonstrate 95% survival against a first LD95 challenge of a given pathogen in an animal model using a therapy developed within 7 days of receipt of an unknown pathogen.
– Demonstrate 95% survival after three LD95 challenges of a given pathogen in an animal model spaced 1 week apart =7 days post countermeasure.
Pathogen Defeat* ($19 million in 2012)
Description: *Previously funded in PE 0602715E, Project MBT-02
Pathogens are well known for the high rate of mutation that enables them to escape drug therapies and primary or secondary immune responses. The Pathogen Defeat thrust area will provide capabilities to predict future threats and to deflect pathogen evolution to non-human spaces such as animals, insects, and bacteria. This area will also determine malicious intent by monitoring key technology acquisitions and commercialization of potential dual-use technologies. Pathogen Defeat focuses not on the threats that are already known but rather on the threats of newly emerging agents and mutations in the future, allowing preemptive preparation of vaccine and therapy countermeasures.
FY 2012 Plans:
– Demonstrate capability of evolutionary pathway of the viral system under multiple selective pressures.
– Use demonstrated capability to validate the algorithms’ predictions.
Use optimized winner system and algorithm to investigate virus mitigation and frequency globally to predict the timing and geographic location of reassortment events.
– Model processes to accurately predict the drift and shift of virus in pre-human animal reservoirs.
– Create viral reservoir specific countermeasures that reduce probability that a novel viral pathogen could transfer from animals to humans.
– Establish partners for transition of immune-hardening and pathogen anti-evolution technologies.