Tag Archives: DARPA Biological Technology Office

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

How to Engineer Bacteria to Search for Underground Chemical Weapons: DARPA

U.S. military researchers asked in 2019 two companies to develop new kinds of biological sensors that can detect underground disturbances or the presence of buried chemicals or weapons.

Officials of the U.S. Defense Advanced Research Projects Agency (DARPA) in Arlington, Va., are looking to Raytheon BBN Technologies, and Signature Science, for the BioReporters for Subterranean Surveillance program.  This project seeks to use indigenous and engineered organisms to sense changes of interest to military commanders in natural and built environments. Raytheon BBN and Signature Science won separate $1.6 million contracts for the Subterranean Surveillance progam.

The two companies will perform laboratory research and proof-of-concept demonstrations of biological sensing systems in well- controlled field tests that take advantage of recent advances in microbial science and synthetic biology to develop biological sensors, signal transducers, and reporters that can reveal subterranean phenomena at a distance.  Bio Reporters should be able to sense a phenomenon at least one meter below the surface, propagate a signal to the surface within seven days, and be continuously detectable on the surface at a distance of 10 meters over the subsequent seven days.

DARPA researchers want Raytheon BBN and Signature Science experts to take advantage of the extensive biological networks that exist underground to monitor large areas to increase the military’s ability to detect subterranean events without the need for precise coordinates.

Excerpts from John Keller, Researchers eye new biological sensors to to detect underground objects like buried chemicals and weapons, https://www.militaryaerospace.com,  Nov. 6, 2019

In more detail  Signature Science and its partner, the Texas A&M University Center for Phage Technology, aim to leverage modern and synthetic phage biology and the straightforward molecular genetics of the harmless soil bacterium Bacillus subtilis to generate a new platform to recognize and report on specific chemical threats underground. The Spore-Phage Amplified Detection (SPADe) method, potentially extensible to explosives, radiation or physical disturbance sensing, seeks to substantially advance currently used techniques which rely heavily on manual soil testing. 

On-Demand Germs: Bioengineering for the Military

From the DARPA website:

The development of increasingly sophisticated techniques and tools to sequence, synthesize and manipulate genetic material has led to the rapidly maturing discipline of synthetic biology. …[But] The costs of maintaining required environmental controls and detecting and compensating for genetic alterations are substantial and severely limit the widespread application of synthetic biology to U.S. national security missions.

To help address these challenges, DARPA has created the Biological Robustness in Complex Settings (BRICS)  BRICS seeks to develop the fundamental understanding and component technologies needed to increase the biological robustness and stability of engineered organisms while maintaining or enhancing the safe application of those organisms in complex biological environments. The goal is to create the technical foundation for future engineered biological systems to achieve greater biomedical, industrial and strategic potential.

“By making these systems more robust, stable and safe, BRICS seeks to harness the full range of capabilities at the intersection of engineering and biology,” said Justin Gallivan, DARPA program manager. “These capabilities could include efficient on-demand bio-production of novel drugs, fuels, sensors and coatings; or engineered microbes able to optimize human health by treating or preventing disease.”

Excerpt from BUILDING THE FOUNDATION FOR FUTURE SYNTHETIC BIOLOGY APPLICATIONS WITH BRICS, July 29, 2014

Predator Bacteria for War

The  Pathogen Predators Program of DARPA would represent a significant departure from conventional antibacterial therapies that rely on small molecule antibiotics. While antibiotics have been remarkably effective in the past, their widespread use has led to the emergence of antibiotic-resistant bacterial infections that are difficult or impossible to treat. In vitro studies have shown that predators such as Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus can prey upon more than one hundred different human pathogens and will also prey on multi-drug resistant bacteria.

The Pathogen Predators program will answer three fundamental questions about bacterial predators:

1) Are predators toxic to recipient (host) organisms?
2) Against what pathogens (prey) are predators effective?
3) Can pathogens develop resistance to predation?

This list [of bacteria that could be killed by predator bacteria] includes NIAID (National Institute of Allergy and Infectious Diseases) Category A and B threats to national security:

NIAID Category A and B
Yersinia pestis (i.e. plague)
Francisella tularensis (i.e. tularemia)
Brucella species
Coxiella burnetii (i.e. Q fever)
Rickettsia prowazekii (i.e.  typhus)
Burkholderia mallei (i.e. glanders)
Burkholderia pseudomallei (i.e. melioidosis)

Source DARRA (pdf)

Synthetic Biology and the Military

Twist Bioscience announced that it raised $26 million in a Series B financing to commercialize the company’s semiconductor-based synthetic gene manufacturing process. Nick and Joby Pritzker, through their family’s firm Tao Invest, led the round, with participation from ARCH Venture Partners, Paladin Capital Group, Yuri Milner and additional strategic corporate and venture investors. All existing investors participated in the round.

The company also received a $5.1 million contract from the Defense Advanced Research Projects Agency (DARPA) to fund development of Twist’s technology platform for the large-scale, high-throughput construction of genetic designs. DARPA granted the contract under the Living Foundries: 1000 Molecules Program, which seeks to build a scalable, integrated, rapid design and prototyping infrastructure for the facile engineering of biology…

Said Emily Leproust, Ph.D., chief executive officer of Twist Bioscience. “Today, we have all the necessary components in place to automate and scale our synthetic gene manufacturing process and staff strategically, with the goal of bringing our first products and services to the market in 2015.”

According to to Twist Bioscience “At Twist Bioscience, our expertise is synthetic DNA. We have developed a proprietary semiconductor-based synthetic DNA manufacturing process featuring a 10,000-well silicon platform capable of producing synthetic biology tools, such as oligonucleotides, genes, pathways, chassis and genomes. By synthesizing DNA on silicon instead of on traditional 96-well plastic plates, our platform overcomes the current inefficiencies of synthetic DNA production, and enables cost-effective, rapid, high-quality and high throughput synthetic gene production. The Twist Bioscience platform has the potential to greatly accelerate the development of personalized medicine, sustainable chemical production, improved agriculture production as well as new applications such as in vivo diagnostics, biodetection and data storage. 

Twist Bioscience Secures $31.1 Million,  PRESS RELEASE, May 27, 2014