This is a gut-on-a-chip prototype device, which may one day be capable of mimicking complex biological processes for drug development. Image source: DARPA, Wyss Institute.
What is the most powerful technology on Earth?
You may think of a B-2 bomber, or a nuclear reactor, or maybe even far-reaching social media platforms. Those are all great answers, but only one technology known to man can heal itself, adapt to its environment, sustain itself for decades, replicate, and evolve: the living organism. If we could harness the power of biology in a predictable manner, then we could create living materials that perform those functions seamlessly, cheaply, and with very low energy requirements.
Hundreds of companies are now attempting to leverage the manufacturing and computational paradigms of biology. Many may still be privately owned, but several are within reach of everyday investors. Industrial biotech Amyris (AMRS +0.00%) has engineered yeast to manufacture over 1.7 million malaria cures, developed tools to digitize genomes to expedite research, and designed novel processes for more predictably engineering organisms. AstraZeneca (AZN +0.00%) is collaborating to research rapid-response therapeutics. And the list goes on.
Given the enormous potential of engineered biology, it should come as no surprise that DARPA, the agency tasked with developing emerging technologies for the U.S. military, is knee-deep in the field. The Biological Technologies Office may not grab headlines away from drone fighter jets and guided bullets, but the work being performed is no less impressive. To find out more about the agency's projects, I reached out to Dr. Alicia Jackson, program manager of the Living Foundries Program. Our discussion is below.
Maxx Chatsko: Many readers may be curious as to why the Department of Defense is investigating biotechnologies and biological systems. What makes biology relevant to the DoD, especially in non-health related applications?
Alicia Jackson: DARPA's mission is to prevent and to create strategic surprise. A new technology vector at the intersection of biology, information science, and engineering holds the potential for significant impact and surprise for National Security. This space of "biology as technology" is becoming tangible due to the rapid, simultaneous development of genome-scale engineering tools, enormous datasets of genome sequences, new imaging and analytical capabilities, and the convergence of advances in information science and engineering with biology. The opportunity is a radically new approach to developing game-changing capabilities across neurotechnology, infectious disease, advanced materials, and programmable biosystems. Biological systems have the ability to do things that no human-made machine or chemistry can begin to approach: the ability to replicate, to learn, to scale from one to billions, to adapt, and to evolve. We can now begin to harness biology's incredibly complex functionality to forward engineer capabilities. It is in the DoD's interest to be ahead of these technologies, rather than trying to catch up with the rest of the world.
One non-medical area of specific interest is that of harnessing biology to make new materials. By gaining control over biological systems and their biochemical pathways -- and designing new pathways by rewriting the DNA "software" in cells -- synthetic biologists are ushering in the "Biological Age," creating substances with not only superior electrical, optical, and mechanical properties, but with properties that we have never seen before in man-made materials: materials that can regenerate, that respond to the environment, that learn and evolve. Ultra light-weight flexible armor, dramatically better anti-fouling and anti-corrosive coatings, and thermotolerant plastics for light-weighting are within sight. Chameleon-like, responsive fabrics, surfaces that harden or flex in response to changing conditions, and extremely efficient, sugar-fueled biological actuators for hybrid robotics are on the horizon, all grown in "living foundries."
MC: Living Foundries is just one of 26 active programs spread across three focus areas being pursued by BTO. With applications ranging from safeguarding engineered microbes to wirelessly repairing the brain to rapidly manufacturing millions of doses of vaccines, there's simply too much to discuss in a single interview. What programs or general themes stand out?
AJ: The office currently has three major thrust areas: outpacing infectious disease, neurotechnology beyond prosthetics, and engineering biology (i.e. programming biological systems). In outpacing infectious disease we are developing a platform for immunoprophylaxis based on gene encoded antibodies to impart immediate immunity, which will be able to pivot toward any emerging infectious disease and be rapidly deployed. As an example of major program in the neurotech space, ElectRx is leveraging control of the body's innate neurophysiology to restore and maintain health -- essentially enabling the body to heal itself.
MC: The field of engineering biology is still emerging, but it holds great potential for transforming multiple aspects of everyday life ranging from obvious applications in health care to less obvious applications in digital storage devices and electronics. What industries will be the first to mature -- and possibly enable investment opportunities?
AJ: It is in DARPA's interest that the investments we are making transition to the commercial market. We would like to see the companies that we work with succeed outside of the realm of DoD. Areas that we are excited about for engineering biology are (1) rapid, scalable, and cost-effective production of millions of doses of vaccines and therapeutics in weeks and (2) the generation of novel chemicals and materials with superior properties that are inaccessible through traditional chemistry (either for chemical or economic reasons).
MC: Many everyday technologies we use today have trickled down to consumers after being researched and developed under DARPA programs. While it's difficult, if not impossible, to predict future consumer applications from current work, what are some possible products or applications that could end up in consumer hands from ongoing work at the BTO?
AJ: One example we can point to is the prosthetic arm developed under the Revolutionizing Prosthetics program. You may be familiar with this, as it has been widely discussed in the media, including a feature on 60 Minutes. DARPA actually took this from inception to FDA approval, which is not our usual model. We have developed other products, which we are transitioning to the warfighter such as our Wound Stasis System that quickly treats abdominal wounds that cannot be subject to pressure. We can imagine many commercial applications for synthetic biology, our vaccine and therapeutics platform, our neurobiology platform, and our other efforts in the neurotechnology realms.
A great example of this is our work with ModeRNA to develop a new RNA-based therapeutics platform to rapidly respond to infectious disease. ModeRNA has been researching mRNA therapeutics for safe and effective gene-based therapies. DARPA gave a seedling contract to the then start-up ModeRNA in 2013, providing the resources necessary to demonstrate pre-clinical efficacy of a therapeutic mRNA platform. This then led to the largest pharma licensing deal ever pursued based on pre-clinical data alone by AstraZeneca for $240M and Alexion for $125M soon thereafter. In 2015, DoD-relevant infectious disease applications of the platform were invested in further through a $100M licensing agreement with Merck and the ModeRNA spin-off company Valera LCC. Also in 2015, ModeRNA closed the largest private funding round in biotech ever, at $450M. ModeRNA now has 145 employees and 45 preclinical product candidates and continues to develop RNAs for effective drug production in humans.
For more on DARPA's work on engineered biology, view Dr. Alicia Jackson's talk at the agency's recent Biology is Technology conference.
