Basic Cadets from the class of 2023 undergo training for Chemical, Biological, Radiological, Nuclear, and Explosive materials (CBRNE) on July 24, 2019. (U.S. Air Force photo/Trevor Cokley)

Engineered Pathogens and Unnatural Biological Weapons: The Future Threat of Synthetic Biology

The COVID-19 pandemic has demonstrated that significant biological threats can and will emerge from nature without warning, demonstrating that a single viral strain can have a profound impact on modern society. It has also demonstrated that infectious diseases can rapidly spread throughout a population without human engineering making them the ideal substrates from which to develop engineered weapons. Viruses and bacteria have been used as weapons for millennia.1 Historically, biological weapons were derived from natural sources, such as anthrax from herbivores and domesticated animals, and smallpox from rodents. Those pathogenic organisms that were found to be suitable for weaponization were cultured directly from the environment; they were then isolated, purified, stored, propagated,a and used to fill biological munitions.2 The most recent of example of this was the production and stockpiling of numerous agents by the biological weapons program of the former Soviet Union. In this program pathogens were selected for specific characteristics directly from the natural environment, propagated, and stored for later use.3 While these pathogens have evolved in nature for the purpose of persisting, they are not optimized for maintenance, storage, and deployment in a military setting. Consequently, while biological agents have not been widely employed as strategic or tactical weapons by state or non-state actors, there are some examples of their use in conflicts. The most significant of these is the well-documented use of crude bacteriological agents by the Japanese army against China during the Second World War.4

Recently, the convergence of advances in computer science, engineering, biological science, and chemistry have made it possible to engineer living systems to optimize growth and increase pathogenicity (the propensity to cause disease). This interdisciplinary approach to providing novel biological functionality has had a positive impact on the biotechnological and biopharmaceutical industries. At the same time, these engineered bacteria and viruses can be co-opted for belligerent purposes. Indeed, the use of designer biological weapons could theoretically give a state or non-state actor an asymmetric advantage over an adversary that favors conventional weapons.

Synthetic biology (SynBio) is the scientific discipline that encompasses all aspects of the engineering of biological systems.5 Beginning with the discovery of the chemical structure of DNAb in the 1950s, SynBio tools such as recombinant DNA technologyc and genome editing toolsd have developed at a fast pace as the fundamental molecular mechanisms underlying biology are discovered. These SynBio tools are lowering the education, training, cost, time, and equipment threshold required to modify and employ pathogenic organisms as biological weapons. The asymmetric threat posed by biological weapons will continue to increase as new tools and techniques are developed and as terrorist organizations become aware of and inspired by the society-wide economic, emotional, and government-destabilizing impacts caused by the COVID-19 pandemic.e Indeed, it can be argued that the total cost of this pandemic—including the loss of life and the stress to the economy—could be rivaled only by the deployment of an atomic bomb. Therefore, developments in SynBio should be continually monitored and reassessed within the context of technological change and its capacity to shift the geopolitical paradigm. In this article, the authors describe how biological systems’ modular nature makes them amenable to engineering, the recent advances in synthetic biology, the impact of synthetic biology on the threat landscape, and the potential policy responses to the maturation of biotechnology in general, and synthetic biology in particular. This article has been developed using both primary and secondary literature sources recently published in peer-reviewed scientific papers.

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