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.
Biological weapons achieve their intended effects by infecting people with disease-causing microorganisms and other replicative entities, including viruses, bacteria, infectious nucleic acids and prions. The chief characteristic of biological agents is their ability to multiply in a host over time.
The threat posed by biological weapons—is especially challenging because of the unique character of these weapons. A prime distinction is the fact that exposure to minute quantities of a biological agent may go unnoticed, yet ultimately be the cause of disease and death. The incubation period of a microbial agent can be days or weeks; unlike a bombing, knifing, or chemical dispersion, a bioattack might not be recognized until long after the agent’s release. Accordingly, bioterrorism poses distinctive challenges for preparedness, protection, and response.
The threat is further compounded by growth of Synthetic biology. In 2002, scientists from the State University of New York at Stony Brook chemically synthesized the complete poliovirus genome, highlighting the transformative potential of SynBio. While this effort was accomplished by experienced professional scientists over the course of years in well-equipped laboratories, the playbook is now freely available and the tremendous advances in molecular engineering techniques since then have only reduced the complexity of this once-monumental effort. This achievement was followed by the first chemical synthesis of a much larger bacterial genome in 2008 and the development of an entirely synthetic cell in 2010.
The use of SynBio tools has endowed scientists with the ability to purposefully dissect the inherently complex series of coupled chemical reactions that compose fundamental cellular metabolism. These networks of reactions can be engineered using modular genes and molecular tools to enhance synthetically produced organisms with desired biochemical properties. Significantly, by combining standard molecular and cellular laboratory techniques with cellular selection (or evolution) strategies, which are accomplished daily by high school and college students in biology classes and research competitions across the world, detailed knowledge of the nature of each chemical reaction is not required to achieve the desired outcome for the engineered biological agent.
A case study in the dual-use nature of these activities can found in the 2017 winning project. A team from Lithuania created a tool to improve the rate of inheritance of genetically altered sequences throughout generations of microbes. While this tool may eventually be used by thousands of researchers for peaceful purposes, there is a possibility that it could be harnessed to develop engineered biological weapons by rapidly altering the genomes of the starting material. The Lithuanian team was just one of 295 teams competing that year. There were 125 from Asia, 84 from North America, 74 from Europe, 10 from Latin America, and two from Africa. This competition and these technologies are truly global in nature, and while they are intended for peaceful and mutually beneficial purposes, the science and tools created may be manipulated by those with bad intentions.
Indian Vice Chief of Army Staff Lieutenant General S.K. Saini while virtually addressing participants at the ‘National Defence Course Bangladesh on post COVID-19 security challenges’, said that “future wars may gravitate towards zero cost wars, wherein a very virulent pathogen may immobilise high-technology arsenal”. He said that “weaker militaries will continue to seek an asymmetric advantage in an unrestricted warfare milieu” while “social media will continue to be the vector of choice for the battle of narratives”.
Bioterrorists and and other state supported actors have at times tried to acquire deadly pathogens and other sensitive biological information. For example, two Canadians were arrested in the city of Buffalo, New York in 1984 after they were suspected of illegally acquiring and smuggling strains of botulism and tetanus to Canada. The Japanese cult Aum Shinrikyo made unsuccessful attempts in 1995 to acquire strains of Ebola from Central Africa to develop the group’s biological weapons program. More recently, two Chinese hackers were indicted in the United States for seeking to obtain intellectual property related to coronavirus treatments and vaccines. Similar incidents were reported in Spain; allegedly Chinese hackers were trying to steal data from Spanish labs conducting vaccine research.
In addition to strategically embedding members into research organizations to acquire these deadly pathogens, some terrorist organizations also have sought to rely on lab insiders to either develop biological weapons or grant access to organisms or sensitive information. For example, a Malaysian scientist tried to develop anthrax weapons for Osama bin Laden, the founder of al-Qaeda.
Threat of Bioaccidents
There is also threat of accidents that can occur in a lab. In one scenario the researchers in a top-level biosafety lab rearrange DNA fragments to synthetically create a live Ebola virus. This pathogen was originally transmitted to people from wild animals, but it has the potential for human-to-human transmission, causing severe (and often fatal) symptoms in humans. These scientists are working on a weakened strain of the Ebola virus to understand its epidemiological characteristics, like the virus’s virulence and transmission factors. While the aim of the research is to develop vaccines or other treatment options that can help save human lives, the manipulation experiment accidently produces a strain of the virus with unexpected characteristics.
For instance, in 2001, Australian scientists hoping to genetically engineer the mousepox virus to render lab mice infertile accidentally created a lethal mousepox virus. In another instance, researchers at the State University of New York developed a synthetic strain of the polio virus in 2002 from chemicals and publicly available genetic information. And the virus that caused the 1918 influenza pandemic—a pathogen that killed an estimated 50 million people globally in 1918 and 1919—was resurrected by a group of U.S. scientists in 2005. In another case, a team at the University of Alberta recreated an infectious horsepox virus, a close relative of the smallpox virus, by ordering DNA fragments online for about $100,000.
There have been instances when the accidental release of pathogens either has led to infections among laboratory personnel or has resulted in disease outbreaks. In another incident, an experienced Russian scientist died of Ebola after accidentally injecting herself with the deadly virus while working on the Ebola vaccine. More recently, almost 3,000 people were infected in China with a bacterial infection called Brucellosis after a leak occurred at a biopharmaceutical company in 2019.
Since these accidents happened in regulated research labs, it was easier to minimize the societal impacts of such mishaps. However, the DIY community involves individuals, enthusiasts, and small organizations dabbling in genetics that are not linked to any formal institutions and hence are not regulated.
Since these groups sometimes have limited formal training on the safety and ethics of using such biotechnology, it might be difficult to contain and mitigate the impact of any accidents that might emerge from their experiments. Even though no unfortunate incident has happened so far, the absence of regulations to monitor this community has emerged as another safety threat.
Synthetic Biology tools allow Bioweapons to be manufactured in fast timescales
The synthetic biology, the design and construction of biological devices and systems, promises to augment biological life, in order to have it producing outcomes which we dictate. Synthetic biology represents an intersection of biology and engineering that focuses on the modification or creation of novel biological systems.Therefore, it combines the knowledge of genomics and chemical synthesis of DNA for the rapid production of catalogued DNA sequences. This branch of science encompasses a wide range of methodologies from various sectors including biotechnology, computer engineering, control & biological engineering, genetic engineering, molecular biology, molecular engineering, systems biology, membrane science, biophysics, and evolutionary biology.
The advances in SynBio have not occurred in isolation. The increase in the understanding of biological systems and the development of the tools of molecular biology that occurred in the late 20th and early 21st centuries were paralleled by commensurate developments in automation, engineering, computer science, and information technology. In particular, the ease of scaling-up the production of bacteria and viruses has increased exponentially in recent decades due to the availability of inexpensive instrumentation for the growth, or culture, of biological material, and the development of standardized reagents such as bacterial growth media by commercial laboratories.
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.
In April 2019, small group of scientists at ETH (German: Eidgenössische Technische Hochschule) Zurich developed a technology which modified a genome using computers within the time frame of one year at 120,000 Swiss francs which is a fraction of the cost of the previous experiments. They could achieve this in the Caulobacter genome, by synthesising 236 genome segments and inserting them into the bacterial genome after joining them together, a process which replaced about one-sixth of the genome. By doing so, the researchers demonstrated the ability to produce strains of bacteria that contained both the naturally occurring Caulobacter genome and also segments of the new artificial genome.
Researchers at the Medical Research Council Laboratory of Molecular Biology in Britain were similarly able to rewrite the DNA of the bacteria Escherichia coli and configure a synthetic genome four times larger and way more complicated than any previously created. Such developments have great potential for the growth of synthetic organisms that have the capability of producing a wide variety of products such as DNA vaccines and other life-saving molecules. On the negative side, we could also use this technology for making bio-weapons. , say US New report .
The Inherent Modularity of Biological Systems leads to Engineering of Bioweapons
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.
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). It has been postulated that molecular modularity evolved as a natural genomic tool, allowing biological systems to rapidly adapt to changing environmental conditions.
In 2005, a group of researchers from the U.S. Centers for Disease Control (CDC), the Mount Sinai School of Medicine, the Armed Forces Institute of Pathology, and the Southeast Poultry Research Laboratory reconstructed the 1918 pandemic influenza virus. This was a particularly striking example of how the modular nature of a viral genome could be used to manufacture a pathogen. The reconstruction was performed by first determining the genomic coding sequences of the virus from lung tissue specimens obtained from pandemic victims who were preserved in permafrost. The relevant DNA sequences were then inserted into a set of circular DNA strands known as plasmids, which were subsequently used to infect host human kidney cells. As predicted, fully functional and replicative viral particles emerged from the kidney cells.
The pathogenicity of the reconstructed virus was evaluated in mice, ferrets, and non-human primates, and it was found that the 1918 influenza strain was significantly more lethal than modern strains. It produced severe damage to the lungs, it stimulated an aberrant immune response, and it led to the development of high viral titers (levels of virus) in both the upper and lower respiratory tracts. The reconstruction procedure was conducted in a standard molecular biology laboratory setting, and all the materials needed for the construction of this viral particle are present in many university biology laboratories. The methods that were employed are not beyond the means of the talented amateur and therefore not beyond the means of a dedicated, well-resourced terrorist organization.
There is currently an effort underway to identify the minimal genome necessary for the survival of the simplest strain of bacteria. 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 enhanced the threat of Biological Weapons
The threat landscape is constantly evolving as advances are made in materials, computational power and speed, and the bioengineering of viruses and cells. While there are challenges to weaponizing a biological system, including contending with the analog nature of biology, the advantages of bioweapons compared to relying on conventional explosives or nuclear weapons include their self-generating properties and the ease in creating a binary weapon allowing for safe production and assembly.
Thus, it is possible for an unsophisticated adversary to design biological weapons with enhanced virulence and infectivity. As already noted, one challenge to weaponizing a biological system is the analog nature of most metabolic circuitry (compared to the digital signals governing much of the electronic world). Further challenges are the presence of significant noise in the normal operation and response of these biochemical circuits and the difficulty in optimizing synthetic pathways while retaining the viability and reproducibility of the living system. However, the use of natural selection techniques in the lab preclude the need for detailed rational design so that an amateur scientist member of a terrorist organization can simply employ SynBio techniques for a large number of cells and select those that perform to the desired effect.
Cells are the fundamental unit of life containing all the molecular architecture required to engage in metabolism (transfer energy), grow, adapt to their environment, respond to stimuli, reproduce, and evolve. Under the right conditions, cells will replenish and increase their numbers if there exists enough food and space. A scientist who has engineered a cell with novel properties can keep producing that system by simply feeding the cells, clearing out the waste products, and harvesting cells when desired. Cell-based systems have co-evolved with viruses that target very specific cell types using lock-and-key-like receptor proteins on both the virus and cell. While viruses rely on cells to reproduce, it is standard lab practice to produce significant quantities of viruses using their cognate cells [cells taken over by the viruses] as hosts. Unlike conventional weapons, biological weapon development requires all the work up front and then the system will reproduce and provide the bad actor with a supply of the weapon as long as the growth-permissive environment is maintained.
SynBio also facilitates the development of binary biological weapons. Although the design and production of binary biological weapons may have been difficult in the past, the ability to engineer and ‘boot-up’ entire genomes has revolutionized the process. With modern synthetic biology tools, an undergraduate student could conceivably engineer and produce two related, non-lethal viruses that are individually harmless. However, following host infection with the two viruses, mixing of the two strains allows for a full restoration and production of highly infectious, pathogenic viruses. Importantly, such genetic mixing has also been documented in nature wherein two or more non-pathogenic poliovirus vaccine strains can recombine to form pathogenic recombinants. Thus, it is not difficult to imagine a non-state actor developing binary weapons consisting of components stored separately for safety in transport and then brought together in a biological munition prior to delivery.
Wide proliferation of Synthetic Biology technology enhanced Bioterrorism Threat
Some authors have argued that the skills and abilities developed over the course of a career in the biological sciences are not available to the amateur and that this may hinder the widespread use of synthetic biology for the development of biological weapons. While this argument may be true for some of the more complex techniques in biochemistry and molecular biology, the techniques used to propagate bacteria and viruses and to cut and paste genetic sequences from one organism to another are approaching the level of skill required to use a cookbook or a home computer.
A vast amount of knowledge would be necessary to describe in detail the biochemistry, genetics, and physiology of baker’s yeast, but anyone with a cookbook, flour, yeast, and sugar can bake bread. Similarly, understanding the algorithms necessary to manipulate images on a computer screen requires expert knowledge, but anyone can point at an icon with a mouse to open it. As technology increases and spreads, those with a simple home laboratory system may be able to manipulate bacterial and viral genes without expert training or years of experience.
In 2018, a small Canadian research group was successful in constructing infectious horsepox virus directly from genetic information obtained solely from a public database for the relatively modest sum of $100,000 in U.S. currency. Horsepox is a genetically distinct relative of the now extremely rare smallpox virus. Smallpox was once a highly feared pandemic disease that either permanently disfigured or ended the lives of millions of people worldwide. The same techniques used to construct horsepox can easily be adapted to construct smallpox with a minimal investment of time and money. SynBio has therefore placed the ability to recreate some of the deadliest infectious diseases known well within the grasp of the state-sponsored terrorist and the talented non-state actor.
Once the purview of scientists with doctorates in microbiology, genetic engineering is practiced every day in high schools and colleges across the world. The instructions, or protocols, for these processes are freely available on the internet and in undergraduate microbiology and cell biology textbooks. Many of the difficulties faced by early microbiologists and cell biologists in the culturing of microorganisms have lessened; indeed, many advanced placement biology programs in high schools across the United States include blocks of instruction on culturing and engineering Escherichia coli (E. coli) and other benign bacterial species.
Today the sophistication of the high school and undergraduate student research projects has matched that of many highly trained personnel who were working in advanced laboratories less than a decade ago. The International Genetically Engineered Machine (iGEM) competition provides another striking example of the ease by which genetic engineering can be mastered at the undergraduate level. At its heart, the iGEM competition is an agreed-upon set of molecular engineering techniques and a large library of DNA parts that are accessed by the competitors in their bid to create novel cellular tools, biological circuits, and gene products. As the competition progressed over the years, the participants have taken advantage of nascent SynBio tools to improve the complexity of their designs. iGEM has helped democratize the science and engineering of biological systems for the benefit of mankind. The organization has dedicated significant resources to biosafety, bioethics, and biosecurity efforts drawing from the expertise of leaders in academia and industry. However, the spread of this information can also enable both state and non-state actors with nefarious intent to employ them in making bioweapons.
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 continue to mature and diffuse throughout the scientific community, as well as among the novice citizen-scientists in the do-it-yourself biology labs that have emerged around the world in recent years. The ability to produce custom-designed bacterial and viral pathogens will enhance the ability of hostile state and non-state actors to develop and deploy relatively inexpensive and efficient biological weapons. Additionally, some of these weapons will likely be engineered with increased pathogenicity, environmental stability, and the ability to withstand the shock of the rapid changes in temperature and pressure that may accompany delivery by explosive warhead.
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. 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.
Policy Responses to the Potential Threats Posed by Synthetic Biology
An effective response to the threats posed by those using synthetic biology for nefarious purpose will require vigilance on the part of military planners, the development of effective medical countermeasures by the research community, and the development of diagnostic and characterization technologies capable of discriminating between natural and engineered pathogens. A 2002 biological warfare counterproliferation study identified six key basic biological research areas that should be emphasized to protect against the threat: human genomics; immunology and the development of methods for the boosting the immune response; bacterial and viral genomics; bacterial and viral assay development; vaccine development; and the development of novel antiviral agents and antibiotics. A continued research and education effort within the Department of Defense will be required to develop and maintain expertise in each of these areas.
The rapid availability of experienced civilian and military personnel is a prerequisite for effective incident response. Therefore, training and education in SynBio, biological engineering, and related disciplines should be emphasized and funded. Many organizations already exist to meet the threat of natural, man-made, and weaponized biological material. These organizations include the Defense Threat Reduction Agency (DTRA); the Chemical and Biological Center (CBC) at Edgewood, Maryland; the Defense Advanced Research Projects Agency (DARPA); the Biomedical Advanced Research and Development Authority (BARDA); the National Institutes of Health (NIH); the Centers for Disease Control (CDC); and United Stated Department of Agriculture-Agricultural Research Service (USDA-ARS) within the United States.
The World Health Organization (WHO), a specialized organization within the United Nations, and several research and response organizations in other countries have historically served similar purposes. Each of these entities deal with systems rooted in the natural world, and while some organizations restrict their focus to naturally occurring threats, they all deal—in one way or another—with the extraordinary pace of technology development unique to the biomedical community. Every advancement in biomedicine is dual-use, and so it is incumbent upon those privileged to work in the scientific field to predict the ways that these technologies might be used for nefarious purpose and to develop the technologies and systems necessary to undermine the efforts of those who might use these unique biological entities as weapons.
There are numerous international treaties and regimes in place to help mitigate the risks at play with biotechnology. Three of the most significant ones are the Convention on Biological Diversity, the Biological Weapons Convention (BWC), and the Australian Group. Each of these agreements or regimes tackles a different aspect of the risk profile—biosafety, bioweapons, and banned substances—but each of them comes with limitations, such as limited scope, sparse funding, and inadequate verification and monitoring mechanisms.
The BWC is a multilateral disarmament treaty banning the development, production, and stockpiling of biological weapons. The BWC, which entered into force in 1975, was the first treaty of its kind to ban an entire category of weapons. In consideration of the inherent dual use problems in biotechnology, the BWC does not outright ban any biological material. Rather, it bans the creation and stockpiling of biotoxins and other biological agents above the amount required for peaceful purposes, and it bans the use of any biological material as a weapon.
Any member of the BWC can initiate a bilateral or multilateral consultation to deal with any problems that come up during the implementation of the treaty. In the event of a suspected biological weapons attack, members of the BWC can report the perpetrating member to the UN Security Council for further action. However, the BWC currently has no mechanism for monitoring to ensure compliance or any means of verification. There is no set threshold for the amount of biological agents “required for peaceful purposes” and without monitoring and verification, there is no way to know if the biological agents a country has are being used peacefully.
The Australia Group is a multilateral export control regime designed by an informal group of countries. The group’s goal is to help countries decide which substances need to be governed by export controls to minimize the risk that exporters may unwittingly assist in the creation of a biological or chemical weapon. The group, first convened in 1985 with fifteen countries and the European Commission, is not a legally binding agreement, but rather a coalition with a shared commitment to the nonproliferation of chemical and biological weapons. The group currently has forty-two members plus the European Commission. The Australia Group claims within its remit eighty-seven controlled compounds, some human and plant pathogens and toxins, and “dual-use biological equipment and related technology and software.”
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