Synthetic biology technology aims to redesign natural biological systems for greater efficiency, as well as create new organisms as well as molecules with desired bio-attributes. These 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 brings together disciplines including biology, chemistry, computer science and engineering. For example it combines the knowledge of genomics and chemical synthesis of DNA for the rapid production of catalogued DNA sequences.
This type of revolution is founded on several core biological technologies, “but it is all about being able to read, write and edit the code of life,” said Tara O’Toole , former undersecretary of Homeland Security for science and technology and current executive vice president and senior fellow at In-Q-Tel, an Arlington, Virginia-based investment firm that works with defense and intelligence organizations. One core technology is DNA sequencing, or the ability to read DNA. Another is DNA synthesis, or the ability to write code for DNA, she noted. “Our ability to write it, to synthesize DNA … is less advanced,” she said. “It’s slower, it’s more expensive, but again we are getting better and better.” Gene editing is another core biotechnology. It allows scientists to alter a DNA sequence by adding, swapping or removing genes. Synthetic biology uses the aforementioned technologies to manipulate multi-cell systems in organisms in a way that can construct new biological parts.
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 has many applications ranging from drug and vaccine development, applications in food and agriculture, manufacturing and diagnostic tests. In the fight against the current pandemic, scientists are turning to synthetic biology to speed up the development of a vaccine. Synthetic biology can be applied to help provide diagnostic tests, including Toehold circuits and in vitro CRISPR-based detection approaches, which could be utilised to test COVID-19 patients.
The importance of Synthetic Biology in commercial market and defense applications has ensued a competition among countries including US and China to lead in it. “Biotechnologies, including synthetic biology, are going to be foundational to the 21st century economy and they’re also going to be a critical arena for global competition in the geopolitical realm,” said Tara O’Toole.
Synthetic Biology is also predicted to transform Defense and Security. Agencies throughout the Defense Department are investing in biotechnologies and working initiatives to harness nature’s processes to better support warfighters. 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. 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. Future advances might include the construction of new biological parts and brain-computer interfaces.
Race among countries to exploit Synthetic Biology for defence
Synthetic Biology is also predicted to transform Defense and Security. 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.
All technology has dual‐use aspects: It can be used for beneficial and harmful purposes. Although synthetic biology applications for beneficial purposes ranging from reducing the burden of disease to improving agricultural yields to remediating pollution hold great promise, it could also employed for malicious uses that could threaten U.S. citizens and military personnel. Synthetic biology expands what is possible in creating new Bio weapons. 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.It also expands the range of actors who could undertake such efforts and decreases the time required.
Synthetic biology, including DNA synthesis and gene editing, increases the number and the severity of threats from potential bioterrorists, according to a report ordered by the U.S. Department of Defense. The John Hopkins Center for Health Security recently hosted a group exercise in which a bioengineered virus called “Clade X” was deliberately released by a violent extremist group, resulting in 150 million dead after 20 months. Loren Thompson of the Lexington Institute warns that synthetic biology could allow the development of “a super pathogen threatening the survival of large populations, and even civilization.”
The United States listed China, Russia, and Iran as countries engaged in dual-use biotechnology research with potential, but unconfirmed, implications for the Biological Weapons Convention, or the BWC. The 2020 report also included a direct indictment of North Korea as a country with an offensive biological weapons program.
Synthetic Biology enables new types of weapons
Synthetic biology could be used to create biological weapons to harm humans. According to the report, released by the National Academies of Sciences, Engineering, & Medicine, “Synthetic biology has the potential to enable new types of weapons,” says Michael J. Imperiale, a microbiologist at the University of Michigan Medical School and chair of the committee that authored the report.
The committee identified three concerns of highest priority, including recreating pathogenic viruses such as Ebola, SARS, or smallpox. The second is engineering bacteria to make them more dangerous, which could be easily accomplished by inserting genes to confer antibiotic resistance. “Capabilities to do either of those have been around for a long time. They are only becoming more readily available,” Imperiale says.
With regard to pathogens, synthetic biology is expected to (1) expand the range of what could be produced, including making bacteria and viruses more harmful; (2) decrease the amount of time required to engineer such organisms; and (3) expand the range of actors who could undertake such efforts.
With regard to chemicals, biochemicals, and toxins, synthetic biology blurs the line between chemical and biological weapons. The major concern is engineering microbes to produce and release toxic biochemicals. “The effects could resemble a chemical weapon or food poisoning,” says Patrick Boyle, head of design at Ginkgo Bioworks and an author of the new report. That scenario is particularly worrisome because it is unclear how long it would take scientists to detect that a maliciously engineered microbe was at play rather than a natural pathogen. High-potency molecules that can be produced through simple genetic pathways are of greatest concern because they could conceivably be developed with modest resources and organizational footprint.
It may be possible to use synthetic biology to modulate human physiology in novel ways. These ways include physiological changes that differ from the typical effects of known pathogens and chemical agents. Synthetic biology expands the landscape by potentially allowing the delivery of biochemicals by a biological agent and by potentially allowing the engineering of the microbiome or immune system.
The report highlights one recently published scientific study that illustrates how easy it might be for people with ill intentions to obtain the DNA necessary to recreate pathogenic viruses. A small team led by virologist David H. Evans at the University of Alberta recently detailed the construction of a horsepox virus, thought to be extinct in nature (PLOS One 2018, DOI: 10.1371/journal.pone.0188453). The project, which was funded with about $100,000 from a pharmaceutical company called Tonix, was controversial because horsepox is a close relative of smallpox, a virus that’s been eradicated in nature for decades. Only the U.S. and Russia retain copies of the virus.
The report emphasizes that many of the traditional approaches of biological and chemical defense will be relevant to synthetic biology-enabled threats, but the field will also present new challenges. DOD and its partners should continue to explore strategies that can be applied to a wide range of threats and also to account for broader capabilities enabled by the field now and in the future. Since synthetic biology-enabled weapons might be unpredictable and hard to monitor or detect, DOD should consider evaluating how the public health infrastructure needs to be strengthened to adequately recognize a potential attack.
“It’s impossible to predict when specific enabling developments will occur; the timelines would depend on commercial developments as well as academic research, and even converging technologies that may come from outside this field,” added Imperiale. “So it is important to continue monitoring advances in synthetic biology and other technologies that may affect current bottlenecks and barriers, opening up more possibilities.”
Synthetic Biology is being used a lot, particularly in China, It’s being used because it is very fast, cheap and relatively easy to use. “China in particular, is pursuing a very aggressive strategy to become the world leader in biotechnology,” she added. A deepened understanding of biotech has moved the world towards a “biorevolution,” O’Toole said during a webinar hosted by the Center for Strategic and International Studies.
There is Rapid Growth of Synthetic Biology in China since December 2008 when the Key Laboratory of Synthetic Biology (KLSynB) was established, marking the government’s first official foray into synthetic biology. Since it’s founding in 2008, the Key Laboratory of Synthetic Biology has grown to over 60 research scientists and 70 graduate students. This group focuses on the development of both theory and technology for synthetic biology, and it’s three stated research fields are: The basic researches for synthetic biology; The innovation of enabling technology and development of engineering platforms for synthetic biology and Nurturing innovation chains from basic research, technology development, and translational research to synthetic bio-manufacturing.
China’s synthetic biology market is flourishing because the Chinese government has laid out ambitious plans to achieve dominance in several advanced technology areas. Key technology areas include biotechnology, artificial intelligence, quantum science, computing, robotics and nanotechnology. The government is investing lots of resources in synthetic biology, by subsidising and funding R&D in this area.
More recently, the 2017 edition of Science of Military Strategy (战略学) — an authoritative textbook published by the PLA’s National Defense University — has introduced a new section on “biology as a domain of military struggle.” This section discusses new potential kinds of biological warfare, including “specific ethnic genetic attacks.” Study of the Chinese military’s interest in biology as an emerging domain of warfare becomes increasingly relevant in the current COVID-19 context, particularly when viewed against the two-decade-old backdrop of emphasis on biological frontiers of warfare put forth by Chinese military thinkers.
Director of National Intelligence John Ratcliffe penned an op-ed in The Wall Street Journal that claims the Chinese government is attempting to enhance the capabilities of soldiers through genetic engineering. Regarding the use of CRISPR in China, Kania and Vorndick noted that many of the ongoing experiments in this field are being conducted at PLA facilities. China’s institutions have emerged as “major centers for research in gene editing and other new frontiers of military medicine and biotechnology,” they wrote.
In 2006, Russia submitted a paper to the Sixth BWC Review Conference on the possibility of advancements in technology leading to the creation of “ethnic weapons.” President Vladimir Putin has made statements on the potential of biotechnology to transform weapons and defense. Russia’s 2015 National Security Strategy highlighted the threatening presence of U.S. military-biological laboratories on Russian borders as well as the importance of developing critical technologies such as genetic engineering for national security purposes.
In January 2015, DOD published a report titled Technical Assessment: Synthetic Biology. It was released by DOD’s Office of Technical Intelligence (OTI), whose mission is to provide “holistic, defense-relevant insights into emerging and potentially disruptive technology to enable U.S. and mitigate adversary technological surprises.” Four major defense applications of synthetic biology were identified: commodity and specialty materials, sensing, medical and human performance modification, and biological and chemical defense, and practical R&D steps were recommended to advance these applications.
The report, U.S. Trends in Synthetic Biology Research, finds that between 2008 and 2014, the United States invested approximately $820 million dollars in synthetic biology research. In that time period, the Defense Department became a key funder of synthetic biology research. DARPA’s investments, for example, increased from near zero in 2010 to more than $100 million in 2014 – more than three times the amount spent by the National Science Foundation (NSF). The new study also found that less than one percent of the total U.S. funding is focused on synthetic biology risk research and approximately one percent addresses ethical, legal, and social issues.
The U.S. Army’s new Futures Command is accelerating research into synthetic biotechnology to help the military develop next-generation living camouflage and other never-before-seen organisms and materials. To help prepare the military to combat adversaries, Team Ignite is “integrating fields like synthetic biology, autonomy and artificial intelligence into our future network,” These technologies will fundamentally change the military’s future operating environment, he added.
“We all know that missions are always safer when our soldiers and their equipment are not detected, and so research in synthetic biology has identified a series of plants that naturally filter light and hide things in plain sight,” said Maj. Gen. John George, commanding general of Army Combat Capabilities Development Command. U.S Army labs have elevated the study of synthetic biology to one of its top ten priorities. New thermal cloaking, insect proof uniforms are on the horizon, if the U.S. can get out in front of China.
“Synthetic biology is one of the Lab’s top ten research priorities. That means we are working across the laboratory and with other regional partners to double the effort that was previously being executed under the Living Materials program,” said Army spokesperson T’Jae Gibson Ellis. The research is being overseen by Gen. Mike Murray, the head of the U.S. Army’s newly established Futures Command.
Army is working to produce materials using biotechnology through its Transformational Synthetic Biology for Military Environments Program, also known as TRANSFORME. “One of the things that we’re really looking to exploit for the Army is if we can harness these low-costs, low-energy routes of production of materials in a forward [operating] context,” said Dimitra Stratis-Cullum, the essential research program manager at the Army Research Laboratory. “Then we can really start to change the equation on logistics and sustainment.” “What we’re doing is trying to build the agility to adapt and push into the rapid genotyping to rapid prototyping space,” Stratis-Cullum said.
Soldier survivability will be one of the key areas of research, Stratis-Cullum said. That’s very different from creating genetically-enhanced super soldiers. Instead, the focus is developing new pieces of technology that will help U.S. troops make it out of battle unscathed. For instance, the effort will place a big focus on developing new biological materials that could be used for cloaking to prevent detection, said Stratis-Cullum.
One of those concepts, she said, is material that could mask an individual’s thermal signature, essentially making them invisible to lenses for cameras that detect heat. “That is one of the areas we are looking at,” Stratis-Cullum said. “We want our soldiers to be able to move and not be detected on the battlefield. We don’t want their infrared signature to be detected. There’s a whole host of signatures that we worry about that could allow them to be targeted.” “We’re talking about trying to make the soldier look like nature, look like natural environments,” she said. “Now we can actually take from nature, so if we could do that in a scalable, stable, limited way, we could bring new concepts to concealment.”
Another potential application would be uniforms that repel insects. “We’re moving [away] from a scenario where we are soaking uniforms in DEET, which is toxic to the soldier, toxic also potentially to the natural ecosystem,” she said. “One of our big pushes is being able to do synthetic biology in a very agile way and very quickly,” Stratis-Cullum said. You really have to harness the precision control and assembly over scale. That’s a big part of the push.”
The final area of focus will be forecasting the future of synthetic biotechnology in the hands of potential adversaries. It’s an area of rising concern. A Russian Molecular biologist Denis Rebrikov recently declared his intention to use a gene-editing tool called CRISPR to create a genetically-modified infant, following in the footsteps of a Chinese scientist who did so as well. “It’s one of the things we look at,” she said. “We try to also look at what is the common barrier, level of control, to what extent that could be implemented in situ [meaning in nature, as opposed to in a lab] in military environments… [we are] trying to really understand that and then use that to forecast.”
Meanwhile, the Air Force Research Laboratory’s manufacturing directorate is working quickly to address an issue brought on by the COVID-19 pandemic. The directorate is one of nine under the umbrella of AFRL and it focuses broadly on material science, manufacturing technology and system support for materials once deployed, said Maneesh Gupta, a materials engineer at the directorate. One research thrust is looking at how to eliminate microbial contamination in a way that is compatible with the materials that are found onboard aircraft, he said.
“Over the last three or four months — as the pandemic has sort of kicked up into high gear — there has been a really important need for the DoD to figure out how they can decontaminate aircraft that had been moving personnel around that might’ve been potentially contaminated with the virus,” he said. The directorate is examining appropriate solutions that will not degrade or hurt the materials that are onboard an aircraft, but will still safely eliminate the pathogen, he noted.
The Office of Naval Research is also looking toward natural systems to support its mission. The organization is working to identify and exploit key principles and organisms from nature and use them as the basis to design and control materials, sensors and devices, said Linda Chrisey, program officer for ONR’s synthetic biology for naval applications. It also wants to use the technology to provide new power strategies for the service. The service’s biocentric technology program is aiming to provide greater capabilities for powering platforms in a variety of environments, she said.
“We do think about undersea powering — the seafloor is becoming an important domain for us,” she said. “We have sensors and communication devices that would like to power for a long time and, of course, accessing those sites can be logistically challenging for many reasons.”
The survivability of platforms in austere environments is also a concern that the office is trying to address. ONR has focused on creating biologically inspired autonomous vehicles where it examines how marine and amphibious animals both move and navigate. “Then [we] extract those principles to develop novel autonomous vehicles both from the platform itself, as well as the control algorithms that allow those vehicles to maneuver and operate in those environments,” she explained.
The rapid pace of information technology advancement in the form of more computing power, better machine learning and image and data analysis software, even 3D printing, are all key contributors to the fast pace of synthetic biotechnology development. That has the United States at an advantage, but it’s not an advantage that will last forever, said Stratis-Cullum.
If we want to maintain competitiveness in biotech and in synthetic biology the first thing we have to do is recognize the national security implications of this and build an effective translational infrastructure. To compete with Beijing, the United States should be measuring and tracking the global “bioeconomy,” including China’s, O’Toole said. More personnel with backgrounds in life sciences and biotechnology should be brought into public service, and a new strategy needs to be created that would improve the U.S. response to pandemics, she suggested. Additionally, the Committee on Foreign Investment in the United States should continue to conduct reviews on China, she said. The committee is tasked with reviewing foreign investments in U.S. companies that could have national security implications.
Although Russia released BIO2020—a whole-of-government strategy for improving the standing of Russia’s biotechnology sector—in 2012, biotechnology research in Russia continues to lag behind that of the United States and China. BIO2020 identifies Russia’s priority areas for
biotechnology research as biopharmaceutics and biomedicine, industrial biotechnology and bioenergetics, agricultural and food biotechnology, forest biotechnology, environmental protection biotechnology, and marine biotechnology
Little information is publicly available on how Russia might employ such dual-use technologies within a military or national security context. However, the accusation that the country recently attempted to assassinate a former double agent for the United Kingdom using a Novichok nerve agent—in violation of the 1992 Chemical Weapons Convention—suggests that it may be similarly unrestrained in weaponizing biological agents, including those derived from synthetic biology. Indeed, the Soviet Union is known to have maintained an extensive, long-standing biological weapons program, Biopreparat, in violation of the 1972 Biological Weapons Convention, writes Emerging Military Technologies: Background and Issues for Congress
Russia has inherited from the Soviet Union a huge arsenal of biological armaments along with a concept of offensive biological warfare. Washington Examiner published, in late February, a story titled “Coronavirus, super-plagues, and why we need nuclear deterrence against biological warfare.” The story gives evidence that “the Russians had developed ‘super-plague’ that would be non-virulent in its stored form, but could easily be converted into a deadly antibiotic-resistant form when needed for weaponization.” What’s interesting, the methodology developed 30 years ago allows for the transformation to take place in a small bioreactor on the weapon itself. The author says he is confidently led to believe that Russian President Vladimir Putin has supervised Russia’s expanded development of biological weapons, in total breach of the Biological and Toxin Weapons Convention, which requires states parties not to develop or acquire biological agents for use as weapons of war.
In early February 2016, the UK Ministry of Defence’s Defence Science and Technology Laboratory (Dstl) announced that it would commit up to £18 million over the next four years exploring the potential impact of synthetic biology on the UK’s defence and security capabilities. Dstl Professor Neil Stansfield stated: “It is important that Dstl keeps abreast of such emerging technologies, ensuring that our armed forces can benefit from cutting-edge capability.”
A statement issued by Dstl stated that it was specifically interested in using synthetic biology to produce ‘novel materials,’ which might provide benefits such as enhanced ballistic protection and lightweight armour or transparent screens and lenses, which don’t mist up. “It is anticipated that within four years a new material for armour, or a new approach to existing materials at reduced cost, will be identified,” Dstl stated. Some of Dstl’s work in the field of synthetic biology includes improved boron carbide armour and catalysts for fuel cells.
Singapore bets big on synthetic biology
Singapore has set its sights on becoming a global powerhouse in synthetic biology. The government is pouring money into a new research programme and is encouraging scientists to make synthetic microorganisms, or redesign natural ones, that can be used to produce food, electronics, medicine and energy.
In January, the government launched a synthetic biology research and development programme, which will receive 25-million Singapore dollars (US$19 million) over five years. Four projects have already received funding. In addition to that investment, grants worth up to half a million Singapore dollars are also available for synthetic biology researchers who collaborate with Chinese peers, as part of a joint scheme between Singapore’s National Research Foundation and the National Natural Science Foundation in China. Researchers have until the end of this month to submit proposals.
The national synthetic-biology strategy prioritizes three areas: developing synthetic cannabinoids, producing rare fatty acids and developing new strains of microorganisms that can be used to create products for industry. “We are not competing to be the best in all areas, we are competing in areas where we have an edge,” says George Loh, who is the director of programmes at the Singapore’ National Research Foundation, which will announce the grant-winners in September.
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