BTO Lays Foundation for a New Generation of Biotech Ventures

DARPA has enjoyed a strong relationship with Silicon Valley since the early 1960s, working with innovators to lay the groundwork for new industries built around Agency investments in semiconductors, networking, artificial intelligence, user interfaces, programming, materials, microsystems, and more. Biotech is now emerging as a breakthrough opportunity space and it represents an area that is ripe for fresh collaboration among DARPA, the nation's top researchers, venture capitalists, and entrepreneurs.

In an effort to harness that potential, DARPA's Biological Technologies Office (BTO) hosted two days of talks last week in Menlo Park, California, that focused on identifying ways to speed innovations from the lab to patients, consumers, and national security practitioners. The meeting—titled "Biotech Startups of the Future"—showcased several of BTO's current programs and research results, including groundbreaking work in in synthetic biology, gene editing, personalized medicine, infectious disease management, and neurotechnology.

"Biotechnology is a 21st century science with the potential to transform the national security landscape and spark the industries of the future, much as aerospace engineering, materials science, microelectronics, and computer and information science shaped the late 20th century," said Justin Sanchez, Director of BTO. "DARPA's work in this space has been extremely productive, but moving from technology demonstration to application and maintaining the United States' first-mover advantage requires the larger science and technology ecosystem to be involved. DARPA and its colleagues across academia, industry, and the investment community must work together to investigate, refine, and develop innovations so that they benefit society at large."

That kind of cooperation in the biological sciences would turn on its head the traditional calls for synergy between commercial innovators and the Defense Department because they're a domain in which DARPA remains an unchallenged pioneer. Due to the high level of technological risk and initial investment involved with moving bio- and neurotechnologies beyond concept phase, DARPA is often among the earliest movers, funding breakthroughs upon which others build.

"In areas such as memory enhancement, real-time health monitoring, living materials, and brain-machine interfaces, the barriers to entry are numerous and many investors are hesitant to take a risk on an unproven idea. In pursuing its mission of gaining a deep understanding of new technologies' function and potential, DARPA eliminates many of those barriers and much of the risk," Sanchez said.

Early commercial transition of DARPA research positions the military to adopt more powerful capabilities at a lower cost in the future after the creativity and competition of the marketplace have evolved technologies to a mature phase and generated new applications. This model has been effective with self-driving vehicles, smartphones and mobile devices, microprocessors, cybersecurity, and more. The life sciences, because they are so foundational and have enormous room to evolve, stand to be even more impactful.

To highlight the level of progress that has been made so far and the investment opportunities that exist, BTO assembled a diverse collection of DARPA-funded researchers to describe their research and results to the Menlo Park gathering. The speakers represented: Ecovative; Phylagen; MIT Broad Foundry for Synthetic Biology; Massachusetts General Hospital / Harvard Medical School; Seromics, Inc.; RenBio, Inc.; National Emerging Infectious Diseases Laboratories, Boston University; Emulate, Inc.; Profusa; University of California, San Francisco; University of California, Los Angeles; Starfish Prosthetics Foundation; Johns Hopkins University Applied Physics Laboratory; and Teledyne Scientific & Imaging.

Among the talks were topics such as:

• Building with Biology Using Engineered Living Materials, which focused on programming DNA to grow materials to specifications at the sites where they are needed and developing living materials that are responsive to their environments and can heal when damaged;
• Staying on Target: Minimizing Off-Target Effects in Gene Editing, which focused on making personalized medicine feasible by conducting rapid, low-cost screens of an individual's likely responses to tailored gene therapy;
• Creating a Pandemic-free World, which focused on DARPA's vision of distributed healthcare that combines technology to detect pandemic outbreaks, rapidly identify and grow potent antibodies to fight infectious disease, and response tools for creating a pandemic firebreak;
• Immunity on Demand, which focused on rapidly developing and delivering nucleic-acid-based protections against infectious disease;
• Failing Faster: De-Risking the Path to FDA Approval, which focused on using organ-on-chip technology to better predict the efficacy of new drugs in the development pipeline;
• A Real-time Window into Your Body's Chemistry, which focused on tissue-integrating in vivo biosensors to continuously monitor physiology over the long term to predict the onset of disease;
• Reinventing Psychiatry Using Neurotechnology, which focused on using implanted, closed-loop neural systems to record and stimulate the brain to treat neuropsychiatric illness;
• MindFlight: Your Brain Will Be Your Pilot Today, which focused on direct neural control of complex physical systems;
• Memory Enhancement in Everyday Life, which focused on non-invasive electrical and auditory stimulation technology to enhance memory by facilitating the neural replay process.

DARPA held a similar meeting in 2016 specifically on the subject of neurotechnology in which BTO leadership laid out a vision for medical, consumer, and national security applications. One year later, Sanchez noted, the conversation is very different as new players have begun to see the technology's potential. "There's a race to get neurotechnology up and running," he said.

During last week's Menlo Park meetings, the timeline BTO laid out for neurotechnology development made clear the pace at which the field has been evolving.

DARPA has been studying brain interfaces since the 1970s, but began investing heavily in the space in 2002 with the launch of the foundational Brain-Machine Interface program, followed shortly thereafter by the Human-Assisted Neural Devices (HAND, 2002) program, which showed it was possible to read motor signals from rodents' brains. Based on the success of that work, the Agency launched the Revolutionizing Prosthetics (2006) and Hand Proprioception and Touch Interfaces (HAPTIX, 2014) programs, which moved the motor advances into humans and expanded the research to close the neural feedback loop by delivering touch sensation through a prosthetic limb to the brain through the central and peripheral nervous systems. In 2009, DARPA launched the Restorative Encoding Memory Integrative Neural Device (REMIND) program to read memory activity in non-human primates. From there, DARPA launched the Restoring Active Memory (RAM, 2013) and Systems-based Neurotechnology for Emerging Therapies (SUBNETS, 2013) programs to pursue breakthroughs in treating memory disorders and neuropsychiatric illness. In 2015, inspired by breakthroughs under RAM, BTO launched the RAM Replay program to pursue memory improvement in healthy individuals going about their daily lives. That technology is on the verge of transitioning to the marketplace.

That rate of progress is equally evident in the area of synthetic biology. BTO program manager Renee Wegrzyn described the Living Foundries program to develop a generalizable platform technology capable of producing almost any molecule on demand and at relevant scales for defense, medical, agricultural, and manufacturing needs. The performers on Living Foundries, Wegrzyn said, are already nearly a third of the way toward meeting DARPA's proof-of-concept goal of producing 1,000 different molecules using modified microbes as the growth platform.

"We've taken a process that was manual, low-throughput, error-prone, and that required Ph.D. expertise, and applied robotics, machine learning, and computational design to transform it into something automated, miniaturized, and high-throughput," Wegrzyn said. "A development cycle that originally took multiple years and upwards of $100 million to synthesize just one molecule of interest has turned into a process that is efficient and predictable thanks to DARPA investment and our refusal to accept the status quo."

Sanchez urged investors to consider working with DARPA and take the next steps toward realizing the commercial potential of the technologies that were presented. DARPA contracting officials were even on hand to facilitate talks. "We're a group that likes to say, ‘Yes,'' Sanchez explained.

BTO is planning future meetings elsewhere in the United States.

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