The Biological Technologies Office (BTO) of the Defense Advanced Research Projects Agency (DARPA) launched an ambitious new program to counter proliferation of weapons of mass destruction. DARPA is interested in diminishing the threat posed by state or non-state actor use of weapons of mass destruction (WMD) and improving diagnostics for troops who may have been exposed to threat agents.
DARPA launched the Epigenetic CHaracterization and Observation (ECHO) program in Feb 2018, that aims to develop a portable device that could identify–within 30 minutes—which pathogen you have been exposed to and when? It could be caused by a virus, bacteria, or in the most extreme catastrophe, a biological agent from a weapon of mass destruction. It would be pretty remarkable for soldiers in the field, but also for civilians seeking medical treatment.
Its success depends on a biological phenomenon known as the epigenome. It seeks to develop technologies that enable the use of an individual’s epigenome to reveal their history of exposure to WMD and WMD precursors.
The epigenome is biology’s record keeper. Though DNA does not change over a single lifetime, a person’s environment may leave marks on the DNA that modify how that individual’s genes are expressed. This is one way that people can adapt and survive in changing conditions, and the epigenome is the combination of all of these modifications. Though modifications can register within seconds to minutes, they imprint the epigenome for decades, leaving a time-stamped biography of an individual’s exposures that is difficult to deliberately alter. It’s thanks to the epigenome that identical twins – who share identical DNA – can differ in health, temperament, and appearance.
DARPA’s new Epigenetic CHaracterization and Observation (ECHO) program aims to build a field-deployable platform technology that quickly reads someone’s epigenome and identifies signatures that indicate whether that person has ever been exposed to materials that could be associated with weapons of mass destruction. Researchers in the ECHO program plan to create a database of signatures for exposure events, so that their envisioned device will be able to quickly scan someone’s epigenome and refer to the database to sort out a diagnosis. The same technology could also serve as a tool for U.S. troops to diagnose infectious disease or reveal exposure to threat agents so that medical countermeasures can be applied in time to make a difference.
Whereas current forensic and diagnostic screening technologies only detect the immediate presence of contaminants, the envisioned ECHO technology would read someone’s epigenome from a biological sample, such as a finger prick or nasal swab, to reveal possible exposure to WMD or WMD precursors, even when other physical evidence has been erased.
“The human body registers exposures and logs them in the epigenome,” explained Eric Van Gieson, the ECHO program manager. “We are just beginning to understand this rich biographical record that we carry around with us. We hope that with the capabilities developed within ECHO, someone in the field will immediately know if a suspected adversary has handled or been exposed to threat agents. The same technology could also serve as a diagnostic tool for our own troops, to diagnose infectious disease or reveal exposure to threat agents, so that medical countermeasures can be applied in time to make a difference.”
“ECHO technology could open up new sources of forensic evidence and make battlefield collection of evidence safer, more efficient, and more accurate,” said Van Gieson. “Additionally, by making it possible to deploy an analytical capability to vastly more locations, we would enhance our ability to conduct global, near-real-time surveillance of emerging threats.”
The program will last four years and be divided into two missions. Researchers on the f ECHO program will solve two primary challenges: to identify and discriminate epigenetic signatures created by exposure to threat agents; and to create technology that performs highly specific forensic and diagnostic analyses to reveal the exact type and time of exposure. To develop this capability, researchers will have to assemble a foundational training dataset of pre- and post-exposure epigenetic readouts in biological samples.
“One difficult part is to put a timestamp on this result, in addition to the sign of which exposure it was — to tell us when this exposure happened,” says Thomas Thomou, a contract scientist who is providing technical assistance to the ECHO program manager. Other questions that remain up in the air for now: Do all humans have the same epigenetic response to the same exposure events? Is it possible to distinguish viral from bacterial exposures? Does dose and duration of exposure affect the signature of epigenome modification?
They will also have to create a device capable of performing multiple molecular analyses and onboard bioinformatics in 30 minutes or less, compared to an average of two days using current lab-centered processes. By the end of the effort, DARPA’s goal is to deliver ECHO capability in a man-portable device that can be used by an operator with minimal training.
“In an outbreak,” says Dr. Thomou, “it will help everyone on the ground immediately to have a rapidly deployable machine that will give you very quick answers to issues that could have far-reaching ramifications for public health safety.”
The ability to partially reconstruct an individual’s history through analysis of the epigenome, however, could have application well beyond national security and thus raise privacy concerns. Accordingly, DARPA intends to proactively engage with several independent ethical and legal experts to help inform the Agency’s research plans, think through potential issues, and foster broader dialogue in the scientific community on social implications