Prions as Bioweapons?
Much Ado About Nothing; or Apt Concerns Over Tiny Proteins used in Biowarfare
Although instances of biowarfare and bioterrorism have been rare in the 21st century, somewhat inconspicuous, but rapidly advancing bioscience and technology that are capable of being weaponized are becoming ever more difficult to surveille, regulate, and govern. One such emerging threat is the growing viability of developing and employing prions as biological weapons.
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In a January, 2019 report to the Senate Select Committee on Intelligence, United States’ Director of National Intelligence Daniel Coats reported that, “…rapid advances in biotechnology, including gene editing, synthetic biology, and neuroscience, are likely to present new economic, military, ethical, and regulatory challenges worldwide as governments struggle to keep pace. These technologies hold…potential for adversaries to develop novel biological warfare agents, threaten food security, and enhance or degrade human performance.”
Prion Proteins & Diseases
Prions (PrPC) are normal, cell-surface proteins that can misfold and aggregate to generate degenerative brain diseases known as transmissible spongiform encephalopathies (TSEs; i.e. – prion diseases). Most notable of the known TSEs are chronic wasting disease (i.e. – “zombie deer disease”; which infects cervids), bovine spongiform encephalopathy (i.e. - “mad cow disease”), and a human pathology, Creutzfeldt-Jakob disease (CJD). CJD can be zoonotically-transmitted by consuming BSE-contaminated meat, and after a long incubation period (e.g.- typically years to a decade) a constellation of neurological and psychiatric symptoms occur.
There are no known cures or treatments for prion diseases; thus, all prion diseases are fatal. Despite international efforts, there are still substantial shortcomings in available methods of detection and decontamination that make public health assessment and mitigation of prion transmission difficult.
Recent developments in prion research may enthuse weaponization of prion agents, and thereby pose threats to national security.
Six Critical Problem Areas for National Security
- Synthetic Prions: Methods to generate synthetic infectious prions have been optimized in attempts to better study and model the disease. Infectious prions can be engineered to be both structurally and pathogenically similar to TSE-producing prions. Although these methods require a certain level of expertise, the production of synthetic, pathogenic prions has been successfully replicated in a number of research facilities worldwide.
Potential problem: Development of prion agents independent of a natural (i.e.- animal) host, thereby making robust production of (weaponizable) prions more viable and readily available.
- Aerosolized Transmissibility: TSEs can be transmitted through aerosolized prion-containing brain fragments. Research has proven that transmission through inhalation of aerosolized prions can infect various animals (e.g., white-tailed deer and mice). Although there is no definite certainty that aerosolizing prion homogenate is a route of transmission for humans, there are studies that support such potential.
Potential problem: A major consideration of any bioweapon effectiveness is ease of delivery. Aerosol dissemination enables a preferred method of delivery, which facilitates use against both individual or group targets.
- Gain of function (GOF): GOF research typically involves augmenting the transmissibility or virulence of a pathogen. In an attempt to better study prions, the (inherently long) incubation period has been experimentally shortened in order to permit more time-effective and –efficient studies.
Potential problem: The increased transmissibility and pathogenicity, and reduced timecourse- of-effect of prions, makes these agents more feasible and valuable for weaponized use.
- Increased knowledge of genomics and proteomics: Progress in genomics and proteomics have allowed varied uses of gene editing technologies. CRISPR/Cas9-based gene edited prion models have been developed that are easier and quicker to produce. As well, recent advances in CRISPR-based allelic drives can precisely target specific sites on genes and can be used to identify and target specific individuals and/or populations.
Potential problem: Simple-to-obtain and rapidly advancing gene editing tools enable modification of prions to more pathogenic and/or transmissible forms, which can be developed for weaponized use with relative ease by both state and non-state actors.
- Cross-species Transmissibility: Studies have shown successful cross-species transmission of prion diseases in laboratory settings. Squirrel monkeys (a non-human primate) are susceptible to CWD. Additionally, studies have shown that genetic variants of mice are differentially susceptible to CWD infections typically seen only in deer.
Potential problem: Demonstration of cross-species vulnerabilities to prions can establish a broader palette of animal vectors for weaponized use for agricultural market disruption and/or zoonotic transmission.
- Interactions with other pathogens: Prions have been shown to influence the pathogenicity of other infectious agents (influenza A viruses, HIV-1, etc.), which could be useful to create synergistic infections to affect particular (or broad) elements of a population.
Potential problem: Coupling known, pathogenic biological agents to prions can generate amplified disruptive effects in targeted individuals and/or groups.
The Non-Kinetic Weaponization of Prions
Although current knowledge, tools, and methods may allow bioweapon programs to produce prion-based agents for kinetic warfare, we posit that the threat of using these agents for non-kinetic engagements is equally, if not more attractive to actors seeking to incur disruptive effects.
For example, prion infections targeting meat markets, animal resources, and prompting public fear could disturb the relative capabilities of regional or global economic and socio-political competitors. The instigating actor/state could then offer viable alternative products or treatments to capitalize on the disruption, thereby establishing relative economic hegemony – and power – in these markets and perhaps on the world stage. If, and when combined with a well-executed misinformation campaign, such an approach could yield multi-domain, multi-dimensional effects that would be iterative, robust, and likely evoke durable consequences.
Countering the Threat of Bioweapons
Clearly, prions are not the only agent capable of such effects. Existing science and technology (i.e. – radical leveling science and technologies, RLT), and newly developing methods and tools (i.e. – emerging science and technologies, ET) can force-multiply non-kinetic engagements that disrupt the extant balances of economic, political, and military power. We believe that it will therefore be increasingly important to analyze, quantify, and predict how particular RLTs and ETs can, and likely will be, employed by foreign competitors and advisories to optimize and/or enhance agents (e.g., prions) for disruptive and/or destructive effects.
Although there are no known bioweapon programs that currently utilize prions and/or prion-based substances, we strongly encourage the US government and international regulators to focus on the current and near-term capabilities of prion research for employment in both kinetic and non-kinetic engagements. Further, in response to such surveillance, we advocate for periodic re-address and re-evaluation of if and how prions are classified on international lists of select bio-weaponizable agents.
For more information and references on the biosecurity risks of prions, please see our work:
- Dead Deer, and Mad Cows, and Humans (?) … Oh My! - Mad Scientist Laboratory Blog (U.S. Army Training and Doctrine Command)
Disclaimer: The opinions presented in this work are those of the authors and do not necessarily reflect the views of the United States Department of Defense, US Air Force, US Special Operations Command, or other institutions/organizations with which the authors are affiliated.
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