Synthetic biology is the application of science, technology and engineering to facilitate and accelerate the design, manufacture and/or modification of genetic materials in living organisms, as defined by the European Commission. It envisions the redesign of natural biological systems for greater efficiency, as well as create new organisms as well as molecules with desired bio-attributes. Among the potential applications of this new field is the creation of bioengineered microorganisms (and possibly other life forms) that can produce pharmaceuticals, detect toxic chemicals, break down pollutants, repair defective genes, destroy cancer cells, and generate hydrogen for the post petroleum economy.
Synthetic Biology is also predicted to transform Defense and Security. New techniques to edit and modify the genome may allow scientists to harness organisms or biological systems as weapons or to perform engineering tasks typically impractical with conventional methods. DARPA wants to utilize the potential of Synthetic biology, to provide on-demand bio-production of novel drugs, new materials, food, fuels, sensors and coatings whatever suits the military’s needs. Future advances might include the construction of new biological parts and brain-computer interfaces.
While DARPA was providing almost no funding to synthetic biology in 2010, the organization had increased its investment to $100 million per year by 2014. Funding increases were followed by the creation of the DARPA program Living Foundries: Advanced Tools and Capabilities for Generalizable Platforms, which sought to increase the speed and decrease the cost of generating new production strains of organisms.
This program started in 2012, and in 2014, Living Foundries transitioned to a new program, Living Foundries: 1000 Molecules, which will invest $110 million through 2019 to enable facilities to generate organisms capable of producing 1,000 molecules of industrial and defense interests. These funds are going to a diverse group of projects. Some are incredibly broad, such as funding provided to MIT’s Broad Institute to advance our ability to assemble large genetic systems. Other projects have a specific, discrete purpose, such as the DARPA–funded biotech startup Ginkgo Bioworks, which is developing probiotics to help prevent common infections for soldiers.
Recognizing the importance of biotechnology, in 2014 the DOD created the Biology Technology Office (BTO), which houses the Living Foundries program as well as numerous others, such as Battlefield Medicine, which is developing platforms for creating medicine on demand in the field, and Safe Genes, a program to create tools for safe genome editing. While the purview of the BTO is greater than synthetic biology alone, further development of synthetic biology tools will result in the application of synthetic biology tools and techniques in greater numbers of projects. Synthetic biology is one of the most important research fields in the present day, and the DARPA approach to synthetic biology research has proven successful so far: the first iteration of Living Foundries succeeded in increasing the speed of creating production strains of new organisms by 7.5-fold, while decreasing the cost 4-fold.
“Just the amount of technological change in that area and the … more capability we have to engineer biology for use, is why I think it’s the most exciting field at DARPA right now, and why we stood up an office in 2014 to focus on it.”
During a discussion with Northeastern University President Joseph E. Aoun at the Center for Strategic and International Studies in Washington yesterday, Steven H. Walker said the life sciences trumps other areas of research as holding the most promise for the future. “That’s the area that I see the most incredible technical leaps and bounds every day,” Walker said. “DARPA researchers looking at how to make gene editing safe and actually reverse a gene edit if they need to,” he added.
While DARPA was providing almost no funding to synthetic biology in 2010, the organization had increased its investment to $100 million per year by 2014. Funding increases were followed by the creation of the DARPA program Living Foundries: Advanced Tools and Capabilities for Generalizable Platforms, which sought to increase the speed and decrease the cost of generating new production strains of organisms. This program started in 2012, and in 2014, Living Foundries transitioned to a new program, Living Foundries: 1000 Molecules, which will invest $110 million through 2019 to enable facilities to generate organisms capable of producing 1,000 molecules of industrial and defense interests.
These funds are going to a diverse group of projects. Some are incredibly broad, such as funding provided to MIT’s Broad Institute to advance our ability to assemble large genetic systems. Other projects have a specific, discrete purpose, such as the DARPA–funded biotech startup Ginkgo Bioworks, which is developing probiotics to help prevent common infections for soldiers.
Another DARPA project is rapid development of vaccines for never-before-seen viruses. “This is about being able to inject the cells in your muscles, say to produce antibodies automatically, for a vaccine that we’ve never seen before, and do it in 60 days or less to protect a large population,” Walker said. “This is work we’ve been funding for about 10 years at universities, and now we are going into clinical trials with this as we speak.”
Creating Synthetic Life through BioDesign Program launched in 2010
In 2010, Darpa invested $6 million into a project called BioDesign, with the goal of eliminating “the randomness of natural evolutionary advancement.” The plan would assemble the latest bio-tech knowledge to come up with living, breathing creatures that are genetically engineered to “produce the intended biological effect.” Darpa wants the organisms to be fortified with molecules that bolster cell resistance to death, so that the lab-monsters can “ultimately be programmed to live indefinitely.”
DARPA under their BioDesign program wants to create living organisms, that can be programmed to live indefinitely, that shall be tamper proof through genetic locks, can be traced using DNA manipulation and could be killed as last-resort through genetically coded kill switch. It’s not totally far-fetched. A team at the NYU Langone Medical Center’s Institute for Systems Genetics has announced the creation a fully functional synthetic chromosome from baker’s yeast, Saccharomyces cerevisiae.
Alicia Jackson, the deputy director for DARPA’s biological program, said biology can do things “that no other technology can come close to doing.” “Biology can replicate itself, it can adapt, it can evolve,” she said. “It can scale from one to millions, to billions, effortlessly in a day, and it’s programmable through its genetic code.” Jackson also suggested that genetically engineered microbes might someday transform Mars and other planets into livable habitats.
DARPA’s Living Foundries Program started in 2012, and in 2014, Living Foundries transitioned to a new program, Living Foundries: 1000 Molecules
According to the DARPA website, the goal of the Living Foundries program is “to leverage the unparalleled synthetic and functional capabilities of biology to create a revolutionary, biologically-based manufacturing platform to provide access to new materials, capabilities and manufacturing paradigms for the DoD and the nation.”
Living Foundries seeks to transform biology into an engineering practice by developing the tools, technologies, methodologies, and infrastructure to increase the speed of the biological design-build-test-learn cycle while significantly decreasing the cost and expanding the complexity of systems that can be engineered. The technologies and infrastructure developed as part of this program are expected to enable the rapid and scalable development of transformative products and systems that are currently inaccessible. Examples include novel materials, industrial chemicals, pharmaceuticals, and improved agricultural products.
The Living Foundries program is comprised of two components: 1) Living Foundries: Advanced Tools and Capabilities for Generalizable Platforms (ATCG) and 2) Living Foundries: 1000 Molecules.
The first component, Living Foundries: ATCG, is now complete. It focused on the development of next-generation tools and technologies for engineering biological systems with the goal of compressing the biological design-build-test-learn cycle by at least ten times in both time and cost, while increasing the complexity of systems that are created. Technical areas of interest included design and automation tools, modular genetic parts and devices, standardized test platforms and chassis, tools for rapid physical construction of biological systems, editing and manipulation of genetic designs, and new characterization and debugging tools for synthetic biological networks.
The ongoing Living Foundries: 1000 Molecules component seeks to further refine this initial capability to significantly decrease the cost, improve the scalability, and expand the complexity of engineered systems for biomanufacturing. Aim is to create a scalable, integrated, rapid design and prototyping infrastructure. Efforts are focused on using automation, novel genome editing tools, and machine learning technologies to alleviate the challenges of prototyping.
As a proof of concept, DARPA aims to produce 1,000 molecules and material precursors spanning a wide range of defense-relevant applications including industrial chemicals, pharmaceuticals, coatings, and adhesives that can be customized to continuously evolving DoD needs while ensuring continued leadership of the United States in the rapidly evolving field of synthetic biology.
“Traditionally we use chemistry to make new compounds or new drugs. But recently we’ve realized that microbes like yeast and bacteria can also produce compounds, and we can program them to make those compounds by first understanding the chemical pathways they use. Take yeast. Yeast uses sugar for a variety of pathways to produce alcohols. If you reprogram those pathways, however, you could potentially have yeast build a variety of different compounds that they weren’t initially designed to make and we would still use the same feedstocks—like sugar. Our teams design the genetic codes that would be needed to reprogram the yeast, explains director of its BTO, neuroprosthetic researcher Justin Sanchez. “They are on milligram quantities of these new compounds, but ultimately, throughout the course of the program, they are scaling up to kilograms.”
The program is looking, for example, at developing a type of plastic that won’t melt when heated. This type of material could conceivably replace metal parts in aircraft, making them incredibly lightweight, Jackson says. They are working on creating a new type of conductive wire. “Can you imagine having conductive wires that you could actually stretch and wrap around — so you could truly just roll up your phone or fold it in half?” Jackson says on an interview.
“We’re interested in something called gene-encoded antibodies,” Jackson says on an interview. “Instead of just giving you a protective antibody straight — the protein itself — we want to encode the blueprint for that antibody in DNA or RNA. The magic about DNA or RNA is that all the cells in your body can read it .The blueprint of DNA/RNA is first read from antibody of recovering patient, these RNA/DNA can be chemically synthesized and transferred to patients. The cells in your body can read that code and generate the antibodies itself. We can give you immunity within hours against any infectious disease.”
Renee Wegrzyn, DARPA’s Living Foundries program manager, said the challenge for the Pentagon is that it lacks bio-manufacturing capabilities to generate molecules and materials that are cost effective, domestically sourced and have high-performance rates for a broad range of applications.
The focus is on “understanding where do current materials and molecules fail, and [where] we can make them better, make them domestically, and … in an agile way,” Wegrzyn said. The program is exploring various manufacturing methods as it pursues the technology, she noted. Living Foundries is also aiming to improve the quality of biological medical countermeasures such as chemical weapon filtration capabilities. “Think of a garment that could bind and neutralize chemical weapons” much like a filter, Wegrzyn said. “We have solutions now, but we know that there’s a gap — that we can make those capabilities better.”
As it works to meet its goals, the 1,000 molecules program is first focusing on the design aspect of biotech. “Design here means finding what is the biosynthetic pathway — what are the genes that I need to layer on here and how can I design that very quickly,” she said. “We have multiple cases where we may in nature identify an enzyme that looks like it should do the trick, but we actually have to test 100 different variants before we find the one that really works the way that we want it to.”
Next the scientists build and synthesize DNA to insert it into organisms in order to produce molecules. They then grow and test the organisms, which can be a time consuming task, she said. “The dirty little secret here is that most of the time it doesn’t work and we actually have to iterate on those designs over and over,” Wegrzyn said. “We have made millions of different variants to learn those rules and apply them and enhance performance going forward so that we can scale this foundry output.” DARPA hit the 1,000 molecules goal more than a year ago and has since manufactured more than 1,500 of them, Wegrzyn said.
That has allowed the agency to “pivot our investing and say: ‘Well, now let’s actually start to make things and test them and see if they can perform better,’” she said. DARPA is working with the Air Force Research Laboratory, the Naval Air Warfare Center Weapons Division and various cohorts in the Army on testing and evaluation, she said. “This is really relevant to the whole military,” she said.
DARPA gave MIT lab $32 million to program living cells to produce products In 2015
MIT has announced its contract with DARPA under which the lab will receive $32 million for engineering cells to find better treatments for disease, make new biofuels, or create fabrics woven with life. “Living cells are the ultimate engineering substrate. They are the most difficult thing out there to be able to control,” says Christopher Voigt, a professor of biomedical engineering and one of the lab’s co-founders, in a video. “Imagine being able to engineer a living cell that can navigate the human body, identify disease, and correct that disease. That requires that the cell be able to sense where they are in the body, be able to detect it, and deliver a therapeutic. And that’s something that biology, we know it can do. But we don’t know how to harness that as part of a medicine.”
The press release states that the grant will enable the Foundry to “offer critical new products in human health, agriculture, and chemistry, and serve as a mechanism for tackling some of the big problems of the world,” over the coming decades. The lab has already created hundreds of man-made nucleotides, and has even found a less resource-intensive way to make fertilizer.
Biological Robustness in Complex Settings (BRICS) program launched in 2015
To date, the work in synthetic biology has focused primarily on manipulating a micro-organism to make a substance, such as penicillin. However, these organisms tend to be fragile, requiring precise environmental controls to survive, and often lose their engineered advantages during the production process.
DARPA under their Biological Robustness in Complex Settings (BRICS) program 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.
DARPA seeks innovative approaches to the development of engineered Forensic Microbial Systems (FMS) that may be deployed in complex environments to create unique microbial signatures for environmental forensics operations. The specific task areas will focus on engineering robust microbial communities that can thrive in a specific environment, the design and detection of molecular signatures to identify that community when placed in complex environments, and mechanisms that will enable the potential safe deployment of the engineered system in open environments. The resulting technology is intended to complement methods being developed for existing microbiome forensics techniques by improving the speed and portability of detection and analysis, and enabling the addition of more advanced functions, such as chemical sensing and logic functions.
DARPA launched BRICS Part 2 in 2017 with goal to develop a synthetic microbiome that contains a unique signature that is easily detected, can be maintained over time in a complex environment, and may be transferred to an object of interest within that environment. Proposals for this final portion of BRICS will delineate practical approaches to the challenges described in this BAA, with limited development of new tools, reagents, or methods. Prior participation in BRICS Part 1 is not a prerequisite for proposing to Part 2, and approaches that leverage technologies developed outside of the BRICS program will be considered.
Soldier: Medical and Human Performance Modification
One of the defence applications is maintaining a soldier’s fighting ability at peak levels by creating medical advances like vaccines before an outbreak, healing soldiers who have severely damaged their bodies, and ensuring the mental health of soldiers is sound. It involves everything from better field cares to improved prosthetics, prophylactic application of bacteria on the skin to prevent infection and to help heal wounds and probiotics that decrease the effects of stress and enhance mental performance. It also involves basic research in molecular genetics and genomics that will enable optimization of soldier cognitive and physical performance.
Walker also said DARPA would like to be able to protect soldiers from disease and chemical or biological warfare agents by modifying those soldiers genetically to make them able to resist. “Can you actually protect a soldier on the battlefield from chemical weapons and biological weapons by controlling their genome, … having their genome produce proteins that would automatically protect the soldier from the inside out?” he said. Walker said making soldiers biologically adaptable to threats is a good idea because it no longer makes sense to have medications or remedies stockpiled for every possible threat.
“You can’t stockpile enough of the vaccine or antivirus capability to protect the population against that in the future. … This is all research at this point — we don’t have the capability yet,” he said. “But that is why you want to be able to actually have your body be the antibody factory, if possible.” Walker said the goal is not to use genetics to make super soldiers, but rather to make soldiers who can be kept safe.
“I think our focus is about the protection aspect and the restoration, versus enhancements,” he said. “All these technologies, they are dual use. You can use them for good, and you can use them for evil. DARPA is about using them for good to protect our warfighters.”
Defense against Biological and Chemical Warfare
“Synthetic biology may enable potential adversaries to develop chemical and biological threat agents with new characteristics. DoD has a responsibility to stay abreast of this field to enable protection for our military personnel, but because biological and chemical weapons defense is focused on threat mitigation instead of enhancing overall DoD capabilities, it is important to keep its size relative to its importance and not allow this aspect to overshadow the major opportunities provided by the field,” according to DOD report titled Technical Assessment: Synthetic Biology.
The historical DARPA approach to protecting against novel bio-threats is appropriate. By developing the capability to respond to any new pathogen, R&D resources benefit DoD and the nation by improving emerging infectious disease preparedness while also enhancing defenses against novel threats. The DoD (mainly DARPA) and healthcare organizations are creating treatments for potential biological and chemical threats to protect both citizens and warfighters. Synthetic biology can assist to combat biological warfare through protein design processes, and by providing a platform to create new biosensor circuits by connecting diverse sensing parts with information processing modules. BTO’s Rapid Threat Assessment program, aims to develop methods and technologies that can map the complete molecular mechanism of a threat agent within 30 days of its exposure to a human cell.
DARPA THoR – Technologies for Host Resilience launched in 2015
The Defense Advanced Research Projects Agency (DARPA) has launched Host Resilience (THoR) program to catalyze the development of breakthrough interventions that would increase the ability of patients own bodies to tolerate a broad range of pathogens. The rising prevalence of multi-drug-resistant pathogens, as well as emerging biological threats, makes developing new medical countermeasures a national security priority. The THoR program will explore the fundamental biology of host tolerance in animal populations with the goal of expanding treatment options for humans in the future.
DARPA and the Army Research Laboratory (ARL) are supporting the research through a $6.4 million contract to Researchers at Emory University, the University of Georgia, and the Georgia Institute of Technology. The research partnership is part of DARPA’s THoR (Technologies for Host Resilience) program and is termed the HAMMER (Host Acute Models of Malaria to study Experimental Resilience) project.
“Malaria is a potentially lethal disease, but resilience in some people and non-human primates allows them to control the disease and avoid adverse outcomes, so that the infection is not incapacitating,” says Mary R. Galinski, Ph.D., professor of medicine and infectious diseases at Emory University School of Medicine, Emory Vaccine Center and Yerkes National Primate Research Center. “Our goals are to identify host features associated with resilience, thinking beyond the host’s immune response into the realms of physiology, biochemistry and pathogenesis, and develop interventions that could enhance that resilience.”
“Our aim with THoR is to lay the foundation for new treatments that would enable the body to more easily and safely cope with infection,” said Col. Matt Hepburn, DARPA program manager. “Among other potential advantages, these new treatments would prevent the body’s overreaction to infection and buy time for the individual’s natural recovery mechanisms to kick in. We want to help patients ‘weather the storm’ during the critical phases of acute illness.” If THoR is successful, it could provide substantial benefits to warfighter health and military readiness. New treatments would help reduce reliance on antibiotics and complement ongoing efforts both to fight microbes themselves and slow the emergence of antibiotic resistance.
Control Systems and Biology: Biological Control Program launched in 2016
Biological Control program seeks to build the foundations for multiscale control of biological systems. DARPA seeks to develop new capabilities for the control of biological systems across scales—from nanometers to centimeters, seconds to weeks, and biomolecules to populations of organisms—using embedded controllers made of biological parts to program system-level behavior.
Specifically, DARPA seeks to develop new capabilities for the control of biological systems across scales—from nanometers to centimeters, seconds to weeks, and biomolecules to populations of organisms—using embedded controllers made of biological parts to program system-level behavior. This program will apply and advance existing control theory to design and implement generalizable biological control strategies analogous to conventional control engineering, for example, for mechanical and electrical systems. The resulting advances in fundamental understanding and capabilities will create new opportunities for engineering biology.
This program will apply and advance existing control theory to design and implement generalizable biological control strategies analogous to conventional control engineering, for example, for mechanical and electrical systems. The resulting advances in fundamental understanding and capabilities will create new opportunities for engineering biology.
Setting a Safe Course for Gene Editing Research through Safe Genes program in 2016
During the second biennial Department of Defense Lab Day May 18, 2017, One AFRL exhibit, called Military Applications of Gene Editing Technology, highlighted research into how geneticists and medical researchers edit parts of the genome by removing, adding or altering sections of the DNA sequence in order to remove a virus or disease caused by harmful chemical, biological or environmental agents a warfighter may have contact with.
The most dramatic possibility raised by the primate work, of course, would be using CRISPR to change the genetic makeup of human embryos during in vitro fertilization. Pentagon scientists are researching gene manipulation to build the soldiers of tomorrow that will be able to run at Olympic speed, and won’t need food or sleep. It will also be possible to trigger the cells of injured soldiers’ bodies to rebuild lost limbs.
In 2016, a Chinese group has become the first to inject a person with cells that contain genes edited using the revolutionary CRISPR–Cas9 technique. On 28 October, a team led by oncologist Lu You at Sichuan University in Chengdu delivered the modified cells into a patient with aggressive lung cancer as part of a clinical trial at the West China Hospital, also in Chengdu.
Using Crispr to cure disease “is probably ethical,” said Eric Hendrickson, a professor at the University of Minnesota Medical School, whose research uses Crispr techniques for DNA repair. “To use that technology to make your child run faster or jump higher is uniformly frowned upon. The technology to do that, however, will soon be in place.” The DARPA’s Safe Genes program aims to deliver novel biological capabilities to facilitate the safe and expedient pursuit of advanced genome editing applications, while also providing the tools and methodologies to mitigate the risk of unintentional consequences or intentional misuse of these technologies.
“Gene editing holds incredible promise to advance the biological sciences, but right now responsible actors are constrained by the number of unknowns and a lack of controls,” said Renee Wegrzyn, DARPA program manager. “DARPA wants to develop controls for gene editing and derivative technologies to support responsible research and defend against irresponsible actors who might intentionally or accidentally release modified organisms.”
From a national security perspective, Safe Genes addresses the inherent risks that arise from the rapid democratization of gene editing tools. The steep drop in the costs of genomic sequencing and gene editing toolkits, along with the increasing accessibility of this technology, translates into greater opportunity to experiment with genetic modifications. This convergence of low cost and high availability means that applications for gene editing—both positive and negative—could arise from people or states operating outside of the traditional scientific community.
DARPA’s Advanced Plant Technologies (APT) program launched in 2017 envisions plants as discreet, self-sustaining sensors
DARPA’s new Advanced Plant Technologies (APT) program looks to seemingly simple plants as the next generation of intelligence gatherers. The program will pursue technologies to engineer robust, plant-based sensors that are self-sustaining in their environment and can be remotely monitored using existing hardware.
Microbes are found in nearly every realm on earth, ranging from thermal vents to Antarctic ice. The spectrum of sensing and metabolic activities that microbes exhibit to thrive in these environments has long inspired efforts to harness microbial biology for sensing and metabolic engineering applications. Sensing, for example, has been achieved with a wide range of different biological components, including enzymes, antibodies, receptor proteins, and nucleic acids
Natural and synthetic biological systems can already sense a wide variety of phenomena of interest, from specific chemicals to light and ionizing radiation. The DoD is looking to utilize natural biologically occurring sensing for their benefit. For example, certain biological systems can naturally or synthetically detect electromagnetic waves, light and ionizing radiation. These organisms can produce physical or chemical signals, which scientists can harvest to create living sensors and detect changes in an environment.
Because of their small size, high sensitivity, ability for self-replication, multiple stimulus sensing ability and the difficulty of distinguishing synthetic vs. organic organisms in the environment, synthetic organisms can become very accurate and discrete sensors for military applications. Potential applications include: distributed tag, track and trace systems and persistent clandestine sensors.
US Naval Research Laboratory (Naval Research Laboratory, NRL) has allocated $ 45 million for the implementation of a program to study the prospects for the use of genetic engineering for the navy. Part of the program was the development of genetically modified microorganisms capable of detecting the presence of enemy ships, submarines, underwater drones and divers.
Some biological systems are able to naturally produce materials that are difficult, expensive, or impossible to produce by traditional means. Potential defense applications include: sensor active materials, high strength polymers for armor, stealth materials, corrosion resistant coatings, biological computing; data storage and cryptographic materials. Arti Prabhakar said that she expects synthetic biology to produce materials “better” by borrowing tricks from nature. Spider silk, for example, is stronger than steel, and abalone shells are tougher than glass and more flexible than plastic. More powerful fuels might also come from genetically engineered microbes, she said.
Commodity materials that the DoD can create using synthetic biology include cheaper textiles and fuels. In the commodity sector, the DoD is investing most in the production of fuels in warzones, such as in Afghanistan, where a gallon of fuel can cost as much as $400.
Synthetic biologists get $1.7 million to engineer world’s strongest biomaterial
Synthetic biologists are attempting to manufacture sporopollenin, the extremely durable biopolymer that forms the outer walls of pollen grains. This naturally occurring polymer coats and protects individual grains of plant pollen, and it’s been found in 500 million-year-old sediments. They’ll get there thanks to a $1.7 million grant from the Defense Advanced Research Projects Agency (DARPA), part of the U.S. Department of Defense.
Synthetic biologists at Colorado State University are attempting to manufacture sporopollenin in the lab using plants, and to control its properties using gene parts designed for specific functions, known as genetic circuits. Their goal is to produce coatings that could one day protect ships, bridges and other infrastructure that crack as they age.
Making sporopollenin in quantities large enough to become commercially viable is a challenge no scientist has yet overcome. This polymer is nature’s original tough nut to crack: So resistant is it to degradation, that scientists have trouble taking it apart and identifying how the polymer is formed.
“The biosynthetic pathway of this polymer is very complex,” Antunes said. “In order to replicate it, we will need to precisely coordinate the expression of several genes in plant tissues that do not naturally produce this polymer.” If the scientists are successful, they will produce a tunable, scalable polymer that can be sprayed onto bridges, hulls and ships, making them impervious to rust or decay.
With proven expertise in making genetic circuits and inserting them in plants, the team plans to transform the tissue of Arabidopsis roots and moss, using their specially designed DNA. Then, the plants should express new genes, and produce the polymer. Plants are ideal to use because they already have a basic biosynthetic pathway in place that the scientists can build on. “Life has existed for billions of years,” Medford said. “Plants have come up with a better way to live on our planet, than we have with concrete and metal. If we can engineer living materials, we can come up with sustainable ways to copy what life has already done so well.”
BioDesign in 2018
As part of its budget for the next year, Darpa is investing $6 million into a project called BioDesign, with the goal of eliminating “the randomness of natural evolutionary advancement.” The plan would assemble the latest bio-tech knowledge to come up with living, breathing creatures that are genetically engineered to “produce the intended biological effect.” Darpa wants the organisms to be fortified with molecules that bolster cell resistance to death, so that the lab-monsters can “ultimately be programmed to live indefinitely.”
Plus, the synthetic organism will be traceable, using some kind of DNA manipulation, “similar to a serial number on a handgun.” And if that doesn’t work, don’t worry. In case Darpa’s plan somehow goes horribly awry, they’re also tossing in a last-resort, genetically-coded kill switch:
Asimov Selected by DARPA to Develop Artificial Intelligence Design Engine for Synthetic Biology in 2019
Asimov, the synthetic biology company building a full-stack platform to program living cells, announced it has been awarded a contract as part of the Defense Advanced Research Projects Agency (DARPA) Automating Scientific Knowledge Extraction (ASKE) opportunity. Through ASKE, Asimov will work to develop a physics-based artificial intelligence (AI) design engine for biology. The goal of the initiative is to improve the reliability of programming complex cellular behaviors.
“To achieve truly predictive engineering of biology, we require dramatic advances in computer-aided design. Machine learning will be critical to bridge genome-scale experimental data with computational models that accurately capture the underlying biophysics,” said Alec Nielsen, Ph.D., Asimov CEO and principal investigator in the program. “As genetically engineered systems grow in complexity, they become difficult for humans to design and understand. For simple genetic systems with only a couple of genes, synthetic biologists typically use high-throughput screening and basic optimization algorithms. But to engineer more complex applications in health, materials, and manufacturing, we need radically new algorithms to intelligently design the DNA and simulate cell behavior.”
Asimov’s founders previously built a hybrid genetic engineering and computer-aided design platform called Cello to program logic circuit behaviors in cells. The ASKE opportunity will seek to support an ambitious expansion in the types of biological behaviors that can be engineered. Asimov’s approach will leverage “multi-omics” cellular measurements, structured biological metadata, and novel AI architectures that combine deep learning, reinforcement learning, and mechanistic modeling. Over the past year, the company has ramped up hiring in experimental synthetic biology, machine learning, and data science to accelerate development of their genetic design platform.
Accelerated Molecular Discovery (AMD) launched in 2020
DARPA is working closely with the Department of Defense (DoD), multiple US government agencies, as well as its academic and industry partners, to provide technical and scientific solutions to address the COVID-19 pandemic.
DARPA’s Accelerated Molecular Discovery (AMD) program is developing new, systematic approaches that increase the pace of discovery and optimization of high-performance molecules to realize capabilities across the DoD. These include simulants and medicines essential to counter emerging threats, to coatings, dyes and specialty fuels needed for advanced performance. AMD systems will provide a comprehensive computational and experimental means to design, discover, validate, and optimize new molecules, iteratively and actively learning to more efficiently and effectively discover molecules that enhance performance in applications relevant to national security.
AMD performers are collaborating with the Walter Reed Army Institute of Research (WRAIR) to apply artificial Intelligence (AI) techniques to accelerate the discovery of drugs to combat SARS-CoV-2. Under this program, the National Center for Advancing Translational Sciences (NCATS) and WRAIR provide medicinal chemistry expertise to MIT and SRI, and also conduct in vitro testing of the AI predictions to validate and inform the models.
Researchers at MIT are concentrating efforts on the development of new AI algorithms that specifically address the problem of data scarcity inherent in studying a novel virus, and are looking to apply such techniques to identify synergistic combination therapies in the future. They recently published blog posts on results from their model trained to predict antiviral activity against COVID-19, and efforts towards the development machine-learning tools to aid in identifying molecules with therapeutic effects against the disease.
AMD performers at SRI International are developing AI tools that incorporate chemist’s expert knowledge, in addition to that learned through data, to discover analogs of existing therapeutics with potency against SARS-CoV-2. They have also recently published data on their related efforts related to the use of machine learning models to identify inhibitors of the virus.
The DARPA Make-It program is automating small molecule discovery and synthesis to propel the field of synthetic chemistry beyond conventional batch-based, intuition-driven capabilities. Make-It is developing artificial intelligence-based approaches to plan and optimize synthetic routes, coupled with methods for fully automated synthesis that include algorithms for automation and process control, interconnected fluidic modules for continuous synthesis, and in-line characterization and purification. Researchers are also working on methods to rapidly explore the vast parameter space associated with synthesis, which has only been minimally sampled by hand thus far. Make-It seeks to provide the foundational technologies required to transform synthetic chemistry to an information-centric science, accelerating the pace of chemical innovation and small molecule manufacturing.
DARPA performers are building a suite of flexible manufacturing capabilities for scalable, resilient production of important medicines:
On Demand Pharmaceuticals’ (ODP)
On Demand Pharmaceuticals’ (ODP) focus is on the production of fine chemical reagents and active pharmaceutical ingredients (APIs), and their technology is based on small-footprint chemical manufacturing devices that were developed in DARPA’s Battlefield Medicine and Make-It programs. Their effort is jointly funded by DARPA and HHS under the CARES Act, and the company enjoyed a visit from FDA Commissioner, Dr. Stephen Hahn, as well as DARPA’s Deputy Director, Dr. Peter Highnam, in December 2020.
SRI International is developing an approach that enables simple scaling of flow-based pharmaceutical production from bench-top to production scale in a single step. Virginia Commonwealth University is building tools to analyze and optimize U.S. based chemical manufacturing to enable rapid reallocation of existing on-shore process streams to critical APIs in a time of need.