Protecting Warfighters In Extreme Environments
by Defense Advanced Research Projects Agency (DARPA)
January 5, 2025

Warfighters operate in environments that stress physiology and present conditions that can compromise health and reduce readiness. Stressors may include too much/little oxygen, extreme heat or cold, pathogens, or endemic diseases such as malaria.

Warfighters often enter these conditions with little or no physiological preparation or protection. Increased preparedness prior to deployment and enduring protection while in theater is needed for service members to operate effectively in these challenging environments.

To address these issues, DARPA’s RBC-Factory program aims to create a platform to modify human red blood cells (RBC) to include additional biologically active components that protect warfighters and allow them to operate more effectively in extreme or threat environments.

Specifically, modified RBCs (mRBC) will be endowed with additional peptides, proteins, or pigments to confer broad yet reversible protection to the recipient for long durations.

“The current state of the art to maintain and protect warfighters operating in extreme environments or facing potential threats requires administration of pre-exposure prophylaxes or post-exposure medical countermeasures,” noted Dr. Christopher Bettinger, RBC-Factory program manager. “But these approaches produce side effects, have limited efficacy, and can be costly. They also present logistical challenges like carrying bulky personal protective equipment or cognitive burdens such as taking oral medications with specific regimes and schedules. RBC-Factory aims to create a device-based approach to imbue RBCs with novel cargoes while precluding genetic modification.”, RBC-Factory program manager. “But these approaches produce side effects, have limited efficacy, and can be costly. They also present logistical challenges like carrying bulky personal protective equipment or cognitive burdens such as taking oral medications with specific regimes and schedules. RBC-Factory aims to create a device-based approach to imbue RBCs with novel cargoes while precluding genetic modification.”

If successful, the 21-month program will deliver two items:

1. Durable Knowledge Product
   Performers will seek to establish the physical and chemical limits of what can be inserted into an RBC. The program further seeks to establish the effect, or lack-thereof, of inserting novel bioactive molecules and materials into RBCs on their physiological properties. Taken together, this durable knowledge product will identify the experimental and practical limits of what novel materials can be inserted into an RBC.

2.  Medical Device Prototype
   The RBC-Factory program will deliver a medical device prototype that can modify RBCs at high rates to meet prospective operational demands. Performer progress across all dimensions of activity will be validated by independent verification and validation (IV&V) partners.

The RBC-Factory program will include an ethical, legal, and societal implications (ELSI) plan to include discussions regarding acceptance, adherence and equity impacts of mRBC platforms. Performer and IV&V teams will connect with ELSI group members at regular intervals to discuss anticipated areas of concern to document the relevant issues and inform technology development.

Defense Advanced Research Projects Agency (DARPA) | U.S. Department of Defense

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