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

• Author: Wickiser, J. Kenneth

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 DNA (b) in the 1950s, SynBio tools such as recombinant DNA technology (c) and genome editing tools (d) 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.

The Inherent Modularity of Biological Systems

Modularity is essential to the purposeful engineering of biological systems to create weapons. In general terms, modularity refers to the ability to replace or update a piece of equipment. For example, a set of interchangeable parts is what allows an individual to modify or optimize a complex piece of equipment, such as a home computer or an automobile. The genetic material (DNA or RNA) of any organism contains all of the information required for its proper functioning and is comprised of many modular components. Specific genes can be removed from one pathogen and inserted into another as a means of altering the activity of the recipient. (6) This modularity enables a measure of predictability of the effects on the complex network of genes when employing molecular engineering methods to insert a foreign gene into a host genome. For example, the modular nature of the non-pathogenic vaccine-strain of the poliovirus genome is what enables it to acquire pathogenicity genes from other viruses and revert to a pathogenic state (horizontal gene transfer). (7) It has been postulated that molecular modularity evolved as a natural genomic tool, allowing biological systems to rapidly adapt to changing environmental conditions. (8) While the process of a virus acquiring pathogenicity has been occurring naturally through horizontal gene transfer for as long as these biological agents have existed, the use of SynBio molecular engineering tools provides a pathway to purposeful and precise changes in genomes on fast timescales not found in nature. Modular genes can be mixed and matched to increase the speed with which organisms can evolve and adapt, producing the type of functionality required of a given environment and providing the organism with a selective advantage compared to its competitors. There is currently an effort underway to identify the minimal genome necessary for the survival of the simplest strain of bacteria. (9) Once it is determined what genes are necessary for survival and reproducibility in bacteria, it may be possible to swap-out non-essential genes for genes conferring any number of desired characteristics. An increased understanding of the modularity of biological systems will impact the fields of biosecurity and military medicine by providing a "molecular toolkit" which can be used for peaceful purposes or by adversaries to design and manufacture biological agents.

Synthetic Biology Enables the Design and Development of Biological Weapons

In 1997, a team of accomplished scientists within a group known as the JASON (f) group met to discuss the future of biological warfare. (10) They identified six emerging biological threats that needed to be monitored by military planners and strategists: (1) the development of binary weapons, (g) (2) the construction of designer genes, (3) the use of gene therapy as a weapon, (4) the development of viruses that evade the immune response of the host, (5) the use of viruses that can move between insects, animals, and humans, and (6) the development of designer diseases. These threats were once considered to be futuristic and speculative. Advances in SynBio techniques, however, have moved many of these predicted contingencies from the realm of speculation into the realm of reality. As the molecular engineering techniques of the synthetic biologist become more robust and widespread, the probability of encountering one or more of these threats is approaching certainty.

The extent and impact of SynBio on future state-on-state conflicts and terrorist violence will increase as the tools and techniques of this discipline...