Tag Archives: DARPA and neuroscience

The Reckless Gambles that Changed the World: darpa

Using messenger RNA to make vaccines was an unproven idea. But if it worked, the technique would revolutionize medicine, not least by providing protection against infectious diseases and biological weapons. So in 2013 America’s Defense Advanced Research Projects Agency (DARPA) gambled. It awarded a small, new firm called Moderna $25m to develop the idea. Eight years, and more than 175m doses later, Moderna’s covid-19 vaccine sits alongside weather satellites, GPS, drones, stealth technology, voice interfaces, the personal computer and the internet on the list of innovations for which DARPA can claim at least partial credit.

It is the agency that shaped the modern world, and this success has spurred imitators. In America there are ARPAS for homeland security, intelligence and energy, as well as the original defense one…Germany has recently established two such agencies: one civilian (the Federal Agency for Disruptive Innovation, or SPRIN-d) and another military (the Cybersecurity Innovation Agency). Japan’s interpretation is called Moonshot R&D. 

As governments across the rich world begin, after a four-decade lull, to spend more on research and development, the idea of an agency to invent the future (and, in so doing, generate vast industries) is alluring and, the success of DARPA suggests, no mere fantasy. In many countries there is displeasure with the web of bureaucracy that entangles funding systems, and hope that the DARPA model can provide a way of getting around it. But as some have discovered, and others soon will, copying DARPA requires more than just copying the name. It also needs commitment to the principles which made the original agency so successful—principles that are often uncomfortable for politicians.

On paper, the approach is straightforward. Take enormous, reckless gambles on things so beneficial that only a handful need work to make the whole venture a success. As Arun Majumdar, founding director of ARPA-e, America’s energy agency, puts it: “If every project is succeeding, you’re not trying hard enough.” Current (unclassified) DAROA projects include mimicking insects’ nervous systems in order to reduce the computation required for artificial intelligence and working out how to protect soldiers from the enemy’s use of genome-editing technologies.

The result is a mirror image of normal R&D agencies. Whereas most focus on basic research, DARPA builds things. Whereas most use peer review and carefully selected measurements of progress, DARPA strips bureaucracy to the bones (the conversation in 1965 which led the agency to give out $1m for the first cross-country computer network, a forerunner to the internet, took just 15 minutes). All work is contracted out. DARPA has a boss, a small number of office directors and fewer than 100 program managers, hired on fixed short-term contracts, who act in a manner akin to venture capitalists, albeit with the aim of generating specific outcomes rather than private returns.

Excerpt from Inventing the future: A growing number of governments hope to clone America’s DARPA, Economist, June 5, 2021

Planting Electronics in Brains

 An implantable brain device that literally melts away at a pre-determined rate minimizes injury to tissue normally associated with standard electrode implantation, according to research led by a team from the Perelman School of Medicine at the University of Pennsylvania. …Thin, flexible neural electrode arrays with fully bioresorbable construction based on patterned silicon nanomembranes (Si NMs) as the conducting component.

“Dissolvable silicon electronics offer an unprecedented opportunity to implant advanced monitoring systems that eliminate the risks, cost, and discomfort associated with surgery to extract current devices used for post-operative monitoring,” said senior co-author Brian Litt, MD,….“This study tested the usefulness of temporary, dissolvable monitoring systems capable of providing continuous streams of data for guiding medical care over predetermined periods of time — from days to months — before dissolving.”

The device is made of layers of silicon and molybdenum that can measure physiological characteristics and dissolve at a known rate, as determined by its thickness. For example, the team used the device to record brain waves in rats under anesthesia, as well as voltage fluctuations between neurons (EEGs), and induced epileptic spikes in intact live tissue. A separate experiment demonstrated a complex, multiplexed array made from these materials that could map rat-whisker sensing capabilities at high resolution.

These electrophysiological signals were recorded from devices placed at the surface of the brain cortex (the outer layer of tissue) and the inner space between the scalp and skull. Chronic measurements were made over a 30-day period, while acute experiments demonstrated device operations over three to four hours.

The type of neurophysiologic features measured by the new device are commonly used for diagnosing and treating such disorders as epilepsy, Parkinson’s disease, depression, chronic pain, and conditions of the peripheral nervous system. “….

This work was funded by the Defense Advanced Research Projects Agency, the Penn Medicine Neuroscience Center,  and others.

See Next-Gen Electrodes: Proof-of-Concept Animal Study Shows that Flexible, Dissolvable Silicon Electronic Device Holds Promise for Brain Monitoring , Press Release, May 5, 2016

See also Nature Materials

The US Military and the Peripheral Nervous System

Bio-Electrical Brains: Military

DARPA has selected seven teams of researchers to begin work on the Agency’s Electrical Prescriptions (ElectRx) program, which has as its goal the development of a closed-loop system that treats diseases by modulating the activity of peripheral nerves…. Ultimately, the program envisions a complete system that can be tested in human clinical trials aimed at conditions such as chronic pain, inflammatory disease, post-traumatic stress and other illnesses that may not be responsive to traditional treatments.

“The peripheral nervous system is the body’s information superhighway, communicating a vast array of sensory and motor signals that monitor our health status and effect changes in brain and organ functions to keep us healthy,“ said Doug Weber, the ElectRx program manager and a biomedical engineer who previously worked as a researcher for the Department of Veterans Affairs. “We envision technology that can detect the onset of disease and react automatically to restore health by stimulating peripheral nerves to modulate functions in the brain, spinal cord and internal organs.”

The oldest and simplest example of this concept is the cardiac pacemaker, which uses brief pulses of electricity to stimulate the heart to beat at a healthy rate. Extending this concept to other organs like the spleen may offer new opportunities for treating inflammatory diseases such as rheumatoid arthritis. Fighting inflammation may also provide new treatments for depression, which growing evidence suggests might be caused in part by excess levels of inflammatory biomolecules. Peripheral nerve stimulation may also be used to regulate production of neurochemicals that regulate learning and memory in the brain, offering new treatments for post-traumatic stress and other mental health disorders.

Circuit Therapeutics (Menlo Park, Calif.), a start-up co-founded by Karl Deisseroth and Scott Delp, is a new DARPA performer. The team plans to further develop its experimental optogenetic methods for treating neuropathic pain, building toward testing in animal models before seeking to move to clinical trials in humans.

A team at Columbia University (New York), led by Elisa Konofagou, will pursue fundamental science to support the use of non-invasive, targeted ultrasound for neuromodulation. The team aims to elucidate the underlying mechanisms that may make ultrasound an option for chronic intervention, including activation and inhibition of nerves.

A team at the Florey Institute of Neuroscience and Mental Health (Parkville, Australia), led by John Furness, is a first-time DARPA performer. Team members will seek to map the nerve pathways that underlie intestinal inflammation, with a focus on determining the correlations between animal models and human neural circuitry. They will also explore the use of neurostimulation technologies based on the cochlear implant —developed by Cochlear, Inc. to treat hearing loss, but adapted to modulate activity of the vagus nerve in response to biofeedback signals—as a possible treatment for inflammatory bowel disease.

A team at the Johns Hopkins University (Baltimore), led by Jiande Chen, aims to explore the root mechanisms of inflammatory bowel disease and the impact of sacral nerve stimulation on its progression. The team will apply a first-of-its-kind approach to visualize intestinal responses to neuromodulation in animal models.

A team at the Massachusetts Institute of Technology (Cambridge, Mass.), led by Polina Anikeeva, will aim to advance its established work in magnetic nanoparticles for localized, precision in vivo neuromodulation through thermal activation of neurons in animal models. The team’s work will target the adrenal gland and the splanchnic nerve circuits that govern its function. To increase specificity and minimize potential side effects of this method of stimulation, the team seeks to develop nanoparticles with the ability to bind to neuronal membranes. Dr. Anikeeva was previously a DARPA Young Faculty Awardee.

A team at Purdue University (West Lafayette, Ind.), led by Pedro Irazoqui, will leverage an existing collaboration with Cyberonics to study inflammation of the gastrointestinal tract and its responsiveness to vagal nerve stimulation through the neck. Validation of the mechanistic insights that emerge from the effort will take place in pre-clinical models in which novel neuromodulation devices will be applied to reduce inflammation in a feedback-controlled manner. Later stages of the effort could advance the design of clinical neuromodulation devices.

A team at the University of Texas, Dallas, led by Robert Rennaker and Michael Kilgard, will examine the use of vagal nerve stimulation to induce neural plasticity for the treatment of post-traumatic stress. As envisioned, stimulation could enhance learned behavioral responses that reduce fear and anxiety when presented with traumatic cues. Dr. Rennaker is a U.S. Marine Corps veteran who served in Liberia, Kuwait and Yugoslavia.

“Using the peripheral nervous system as a medium for delivering therapy is largely new territory and it’s rich with potential to manage many of the conditions that impact the readiness of our military and, more generally, the health of the nation,” Weber said. “It will be an exciting path forward.”

Press Release: Work Begins to Support Self-Healing of Body and Mind
Integrated, international efforts under ElectRx program blend mapping of neural circuits and development of novel bio-electrical interfaces  OUTREACH@DARPA.MIL, Oct. 5, 2015