Assessing Threats of SynBio – Three Challenges

By Prof. Margaret E. Kosal, Sam Nunn School of International Affairs, Georgia Institute of Technology

In April 2021, Mikhail Kovalchuk, President of Russia’s Kurchatov Institute, was quoted as saying “[t]he artificial cell, on one the one hand, is medically important. It can be a diagnostician, it can be a targeted drug deliverer, but on the other hand, it can be harmful, yes, and then in fact one cell that has a genetic code and develops itself is a weapon of mass destruction.”

Kovalchuk’s assertions have a resonance with the words of then-US Director of National Intelligence (DNI) James Clapper when advances in gene editing were included in the list of threats posed by “weapons of mass destruction and proliferation” in the 2016 annual Worldwide Threat Assessment Report to the US Congress.

Synthetic Biology, often referred to as SynBio, is one of a set of emerging science and technology (S&T) fields that is heralded as potentially being the source of transformational capabilities carrying the potential to revolutionize governmental structures, militaries, economies, and life as we know it; others have argued that such technologies will yield doomsday scenarios and that military applications of such technologies have even greater potential than nuclear weapons to radically change the balance of power.

While the suggestion that such emerging technologies will enable a new class of weapons that will alter the geopolitical landscape remains to be realized, a number of unresolved security puzzles underlying the emergence of potentially disruptive technologies have implications for international security, defense policy, governance, and the future of military forces. Some of these technologies, like SynBio, have a special significance for chemical and biological defense and counter-proliferation efforts.

In thinking about the future of warfare, one often encounters two ideological camps: those who prioritize the role of technology and those who do not. One must always be cognizant and skeptical of slipping into a technological deterministic mindset. That is the notion that technology alone, or is even the most important factor, can determine the outbreak or outcome of conflict. The wars of the last two decades also should remind us all that co-option of broadly available commercial technologies may present the most significant operational threat, e.g., cellphone activated improvised explosion devices (IEDs) in Iraq and other places. At the same time, to deny or dismiss the role of technology in effecting the outcome (as well as outbreak) of war and conflict is also perilous. Neither purist ideology is manifested in the operational world. Contemporary analyses and policy debates often expose the tenuous links or disconnections among mainstream scholarship on international security and war (or strategic) studies, geopolitics, understanding of the defense technological innovation and acquisition processes, and fundamental understanding of the underlying science. In addressing synthetic biology, three important technical concepts must be acknowledged. First, SynBio is not a discrete homogenous thing. One of the most well-known tools of SynBio is the advanced gene-editing technique known as CRISPR, which is a bacteria-derived system that uses proteins to “cut and paste” selectively into a genome. CRISPR isn’t the only advanced gene-editing system out there. There’s no single SynBio system to target when trying to assess potential threats, even within gene-editing. Another example of a SynBio technique or process, which gets less popular attention, is cell-free synthesis (CFS). It is a method or platform to produce something, mostly small molecules like chemicals and proteins. CFS can serve as replacement platform or alternative production means for something when cell-based systems are problematic. The idea and practice of cell-free synthesis goes back to the late 1800s when Eduard Buchner (of Buchner funnel ‘fame’) synthesized alcohol via organic chemistry. In the late 1950s, cell-free synthesis was heralded when the iron-carrying blood protein, hemoglobin, was first produced in a laboratory. That was a long arduous pathway. It was significant because it demonstrated that complex, biologically-important molecules could be created outside of biological systems. The current state of the art is a direct result of earlier investments in basic research and development of new instrumentation and techniques, including genetic engineering, in the ensuing decades. SynBio makes things more efficient and much less arduous, which make them more readily available to more groups and people. Even the ‘easiest’ CRISPR synthesis is harder and requires more tacit knowledge and specialized equipment than construction of an IED. The knowledge and skill required is well within the capacity of most states and large transnational corporations, whereas it’s unlikely to in the case of terrorists

Metabolic engineering and microbial cell factories (MCF) are another aspect of SynBio that bridges technique, process, and products. Microbial cell factories are means to produce materials, such as on-site synthesis of fuels, specialty chemicals, or other commodities that is not dependent on petrochemicals. They also have potential to function as self-healing materials, as corrosion inhibitors, or for in situ repair of abiotic materials. MCF have been referred to as “3D printing for molecules.” Advanced gene-editing techniques, like CRISPR and other systems such as TALENS and Zinc Finger Nucleases, are likely to be incorporated into MCF in order to more efficiently, or perhaps even more environmentally-responsibly, produce commodity or specialty materials. It is possible to imagine a scenario in which CRISPR is used to make an MCF that produces a toxic compound. Much of the same underlying science and engineering that enables one to conceive of a material to inhibit corrosion is the same or very similar to that which creates something that can cause or accelerate corrosion, i.e., an anti-materials agent. At the same time, transitioning something in a laboratory to operational conditions is not trivial.

Second, there is no single or even a couple scientific disciplines on which to focus attention when considering the implications of synthetic biology. Breakthroughs and discoveries come from molecular biology, chemistry, physics, and multiple engineering fields. Perhaps the single easiest way to tell someone is not familiar with cutting edge research is if they attempt to restrict focus to any single discipline. Finally, and perhaps adding the greatest amount of complexity – synthetic biology is fundamentally dual use in its nature. It’s a dual use technology, by both meanings of the term. Historically and in the nuclear policy world, dual use means a demarcation between civilian and military uses. In the life sciences and much of cutting-edge scientific and engineering research, dual use refers to the concept that the same or similar techniques, manufacturing elements, and processes used for beneficial purposes could also be misused for deleterious purposes. Almost all the equipment and materials needed to develop dangerous or offensive agents, particularly biological and chemical agents, have legitimate uses in a wide range of scientific research and industrial activity, including defensive military uses. Advances in synthetic biology and gene-editing specifically not only potentially pose security and proliferation concerns, but they also may enable new capabilities for defense, detection, and verification of biological agents, as well as diagnostic capabilities for emerging infectious diseases, like COVID-19, and multiple other beneficial outcomes beyond therapeutic gene-editing. The dual use nature of SynBio – and much of modern S&T – adds further complications to governance, response, and risk mitigation.

In the late twentieth and early twenty-first century, the world has struggled – and continues to do so – to deal with the proliferation challenges of new technologically-enabled weapons, especially in the life sciences. The potential synergies between synthetic biotechnology and other emerging technologies, such as additive manufacturing, the cognitive neurosciences, nanotechnology, and big data analytics, not only suggest tremendous potential for advancement in technology for beneficial applications but also raise new concerns.

The Royal Swedish Academy of Sciences recognized CRISPR as being “incredibly powerful for improving the human condition” by in awarding the 2020 Chemistry Nobel Prize to two of its developers. CRISPR and other advanced gene-editing techniques represent high-profile topics that generate a great deal of attention and hope. As Russia’s Kovalchuk and US DNI Clapper noted, there are also potential security concerns. Delineating a list of imagined or potential threats is not likely to be the most effective way to address challenges of SynBio, or many other emerging S&T capabilities, however. That is rarely a high-fidelity pursuit except in retrospective cherry-picking of scenarios from favorite science-fiction stories, and one should be skeptical of any one or group that claims they can do such. Paradoxically, it is likely to be counter-effective by narrowing an aperture, impeding legitimate research, missing threats, and enabling those who would use such technology to do harm, minimally by calling attention to what we see as harmful. How, when, where, and in what form the shifting nature of technological progress may bring enhanced or entirely new capabilities, many of which are no longer the exclusive domain of any single state, is contested and requires better analytical tools to enable assessment and understanding.


Dr. Margaret E. Kosal is Professor in the Sam Nunn School of International Affairs at the Georgia Institute of Technology. Formally trained as an experimental scientist, she earned a doctoral degree in Chemistry from the University of Illinois at Urbana-Champaign (UIUC) working on biomimetic and nano-structured functional materials. Kosal is also the co-founder of a sensor company, where she led research and development of medical, biological, chemical sensors and explosives detection. She has previously has served as a Senior Advisor to the Chief of Staff of the U.S. Army, as Science and Technology Advisor within the Office of the Secretary of Defense (OSD), and as an Associate to the National Intelligence Council (NIC).