A New Age of Bioterror: Anticipating Exploitation of Tunable Viral Agents.

• Author: Hummel, Stephen

The emergence of the SARS-CoV-2 virus in Wuhan, China, in November 2019 and its subsequent worldwide spread has had tremendously destabilizing effects, which are still being felt more than two years later. Lessons from COVID variants include immediate impacts at the local level (initial variant), global pandemic effects from the Delta variant to include significant and protracted economic impact, and the more sub-lethal, sustained economic, political, and healthcare impacts of the Omicron strain. The global SARS-CoV-2 pandemic has also highlighted the ongoing biological revolution that has resulted in the rapid development and employment of new diagnostic tests, vaccines, and other targeted treatments including monoclonal antibodies and antiviral drugs. Over the past decade, the intersection of technology (e.g., computer science, automation, DNA sequencing) and biology has expanded exponentially, becoming embedded in economies and society. This intersection, along with the demonstrated impacts of SARS-CoV-2, is fraught with opportunities and risks. The tools for curing genetic diseases, reducing the effects of climate change, and generating sustainable food sources are now being developed and tested. Yet, these same gene editing tools could be employed to generate and modify biological weapons, making it important for both the counterterrorism community and scientific community to anticipate how the scientific advances may change the bioterrorism threat landscape. (1)

In this article, the authors consider the theoretical potential for bioterrorists to select a viral platform and genetically modify viral transmissibility, incubation and infectious time windows, and lethality along with the manner of death, creating what are in essence tunable bioweapons. Such bioweapons could achieve targeted effects tailored to timescale, physical and psychological effect, with intended tactical, operational, and strategic levels of impact, with the most impactful viral agents producing all three effects.

To anticipate the potential future threat posed by tunable viral agents, the article first examines the advancing biotechnological toolkit that bad actors may be able to exploit. It then delves into the singular threat posed by viral agents compared to other potential forms of weaponized pathogens such as bacteria, with the COVID-19 pandemic underscoring the threat posed by highly transmissible viruses. The next section describes how biotechnology tools allow for the bioterrorist to select a viral "chassis" and then prospectively genetically tune the respective system variables of lethality, transmissibility, and infectious window for tactical, operational, or strategic effects, or, to maximize impact, combinations thereof. The piece then discusses the duality of emerging biotechnology tools for developing and deploying potential bioweapons as well as their countermeasures. The article closes with some concluding observations.

The Advancing Biotechnology Toolkit

While there is a variety of biological gene editing tools, perhaps the most notable is the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) Cas9 system. (2) This system comes from the adaptive immune response of bacteria to prevent viral infection. During the process of viral invasion, the virus hijacks the host cell to replicate its genetic material to make multiple copies of itself to infect other cells. Bacteria utilize the CRISPR system to identify the invading viral genome and to subsequently cut the viral genetic material using the associated Cas9 protein. The critical capability of the bacterial CRISPR-Cas9 system is the recognition of the pathogen genome using a target sequence that is complementary to a portion of the target viral genome. The CRISPR can then quickly identify a known invader's genetic code and rapidly digest and incapacitate it upon recognition.

The great technological leap of CRISPR is its application to edit plant and animal genomes. With several advancements in biotechnology, including rapid and affordable whole genome sequencing and nucleic acid (DNA and RNA) synthesis, both scientific investigators and prospective bioterrorists with the requisite scientific knowledge and equipment can now with relative ease design and manipulate specific target sequences to modify, insert, or delete portions of the genetic material. The ease of 'copy/cut/paste' modifications of specific genetic sequences has the potential to cause either a loss or gain of biological function. While the potential impact on human diseases can be tremendous, as evidenced by recent news of a patient being possibly cured of HIV infection, (3) so too can the negative consequences. In 2018, Dr. He Jiankui, a Chinese biophysicist, employed CRISPR to delete a portion of the CCR5 gene in embryos with at least one HIV-positive parent. The CCR5 gene "encodes a protein that allows HIV to enter immune cells," and a small deletion (CCR5-delta32) therein had been previously shown to protect cells from HIV infection. (4) This use of CRISPR not only shocked the world but was also undertaken without the consent of the Chinese government. Jiankui was subsequently found guilty of "illegal medical practice" and sentenced to three years in prison, while several of his colleagues received shorter sentences. (5) Even though Jiankui was an established scientist, his employment of CRISPR to edit human embryos less than six years after the 2012 Science article by Jennifer Doudna and Emmanuelle Charpentier first reported the programmable nature of CRISPR illustrates its relative ease of use. (6)

The combined lessons of the COVID pandemic, along with an increasing effective biotechnology toolkit, add to a possible playbook for bioterrorists who seek to use viral platforms to achieve effects along a continuum of targeted, local endemic effects all the way through to inducing a global pandemic. This playbook might also be leveraged by state actors or state actors through proxies.

The Singular Threat of Viral Agents

The suite of viral outbreaks in the 21st century, including COVID-19, Ebola, Zika, SARS, MERS, swine flu, and avian flu, readily highlights the dangers of these highly transmissible agents. When factoring in their respective varying lethality, routes of infection, and overall infectivity, viral agents clearly pose a considerable security threat...