Program Summary
The Technologies for Host Resilience (THoR) Program aims to develop new methods to maintain and optimize force health in the face of new and emerging infectious diseases. The goal is to discover the molecular mechanisms for tolerance of infection in animals, and develop therapeutic strategies that modulate the resilience of humans against infection. This capability would support military readiness by enabling warfighters to weather the storm of infectious diseases in low-resource or remote settings where pathogen-specific therapeutics or intensive care unit capabilities may not be locally available.
Current treatments for infection focus primarily on host response mechanisms based on resistance to a pathogen, meaning the host maintains fitness by inhibiting the pathogen—often with drugs—gradually reducing pathogen load. This approach frequently relies on a priori knowledge of the pathogen, is limited to a discrete set of pathogens, and has imposed evolutionary pressures leading to the increased prevalence of drug-resistant organisms. In contrast, the THoR program focuses on host tolerance rather than on directly attacking the pathogen, effectively exploring how a host can maintain fitness despite active infection by a pathogen.
THoR performer teams are developing approaches and methodologies to identify mechanisms of tolerance and characterize the key biological drivers of that response. DARPA aims to replicate those pro-tolerance mechanisms in hosts using a single intervention or combination of interventions to improve health and reduce mortality.
The program is organized into three technical areas:
- 1) Discover Tolerant Populations: perform animal studies to examine intra- and inter-species differences in host fitness; identify sub-populations and species that are tolerant to infection;
- 2) Identify Biological Mechanisms of Tolerance: define and characterize the basis for tolerance across multiple biological scales (i.e., species, tissues, and cells); and
- 3) Identify and Validate Pro-Tolerance Interventions: recapitulate pro-tolerance mechanisms in susceptible hosts using small-animal and large-animal models to demonstrate improved survival.
The long-term objective of the THoR program is to integrate the new methods and tools into an end-to-end pipeline for discovering novel host-centric countermeasures against infectious diseases.