Rapid Threat Assessment

The Rapid Threat Assessment (RTA) program aims to provide critical information to speed production of medical countermeasures to protect U.S. forces against novel chemical and biological weapons. Such weapons have historically been mass-produced within a year of discovery. Development of countermeasures, however, currently takes far longer. Using current methods and technologies, researchers require decades of study to gain a cellular-level understanding of how new threat agents exert their effects. This temporal gap between threat emergence, mechanistic understanding, and potential treatment leaves U.S. forces vulnerable, so DARPA launched the RTA program with an aggressive goal for researchers: develop methods and technologies that can, within 30 days of exposure to a human cell, map the complete molecular mechanism through which a threat agent alters cellular processes.

Threat agents, drugs, chemicals, and biologics interfere with normal cell function by interacting with one or more molecules associated with the cell membrane, cytoplasm, or nucleus. Since a human cell may contain up to 30,000 different molecules functioning together in complex, dynamic networks, the molecular mechanism of a given threat agent might involve hundreds of molecules and interactions. RTA performer teams are developing high-throughput tools and methods to detect and identify the cellular components and mechanistic events that take place over a range of times, from the milliseconds immediately following threat agent exposure to the days over which alterations in gene and protein expression might occur. The molecular mechanism must also account for molecular translocations and interactions that cross the cell membrane, cytoplasm, and nucleus.

Rapidly understanding the molecular mechanism of a given threat agent would provide researchers the framework with which to develop novel medical countermeasures and mitigate threats. If RTA is successful, potential adversaries will have to reassess the cost-benefit analysis of using chemical or biological weapons against U.S. forces that have credible medical defenses. Successful RTA technologies would also be readily applicable to drug development and combating emerging diseases. In both cases, detailed knowledge of molecular mechanism would facilitate approval of new drugs by shortening the time needed to evaluate drug efficacy and toxicity.