Abstract: Bioscience and biotechnology advances offer extraordinary promise, but they are also accompanied by emerging biological risks—specifically the potential for catastrophic accidents or deliberate misuse by malicious actors seeking to cause harm. These risks include the possibility that non-state actors could exploit the legitimate global bioscience research and development enterprise to gain the knowledge and materials to develop and disseminate a biological weapon. We must take action to safeguard the life sciences to prevent biotechnology catastrophe, in addition to bolstering law enforcement and intelligence capabilities to more effectively anticipate and prevent bioterrorism and other biological threats.
The COVID-19 pandemic has revealed that countries around the world are woefully unprepared to prevent and respond to pandemics. The SARS-CoV-2 virus has infected more than 520 million people, killed more than six million, and caused trillions of dollars in economic damage.1 The events of the past two and a half years have highlighted the world’s vulnerability to future high-consequence biological events, which could cause damage as severe as the current pandemic or possibly much worse.
This article outlines the actions that governments, the private sector, and civil society can take to prevent a catastrophic act of bioterrorism and how to guard against exploitation of the life sciences and biotechnology. It first outlines the changing biorisk landscape and gaps in oversight, before discussing approaches for preventing biological attacks. Next, it provides a proposed threat reduction strategy and outlines initiatives by the Nuclear Threat Initiative (NTI) to develop a more comprehensive approach to biosecurity, which helps fill gaps in oversight. The article then examines how intelligence and law enforcement capacity to prevent bioterrorism can be bolstered, before offering final thoughts on the path forward.
The Biorisk Landscape
In addition to the large loss of life from the COVID-19 pandemic—with more than a million deaths in the United States alone2—recent events in Ukraine have further highlighted biological risks. Russia’s disinformation campaign alleging bioweapons development in Ukraine’s legitimate bioscience laboratories has led to concerns that Russia may itself use chemical or biological weapons in Ukraine as part of a false-flag operation.3
Along with concerns about state bioweapons risks and global pandemics that could be caused by a naturally emerging infectious disease outbreak or an accidental laboratory release, the world also faces biological risks posed by non-state actors—specifically that they could attempt to develop or acquire a biological weapon and use it. The impact of a bioweapons attack by a terrorist group could range from local damage on a relatively small scale to a catastrophic biological event with global reach. Efforts to guard against high-consequence biological events must therefore include efforts to guard against bioterrorism. Unfortunately, these risks are only growing over time as rapid technological advances drive emerging biological risks.
Bioscience and biotechnology advances offer extraordinary promise; they are critical for advancing public health and pandemic preparedness, helping guard against climate change, and fostering economic development.4 A classic example is rapid progress in developing capabilities to read, write, and edit DNA, which encodes the underlying designs for all life on earth. This is part of a wider revolution in the biosciences that is driving advances in fundamental capabilities to engineer biology—including accelerating cycles for developing, building, and testing new designs for biological systems. This includes new, more efficient tools for automating high-throughput bioscience experiments, coupled with ongoing advances in artificial intelligence-based approaches. Twenty-first century bioscience is often described as a revolution, with exciting potential future gains over the horizon,5 and this enthusiasm is often warranted. However, these rapid developments can also pose important challenges—increasing risks of deliberate exploitation or accidental misuse of the tools of modern bioscience and biotechnology—with potentially catastrophic consequences.
These are not new risks, but they have been compounded by the current pandemic, which has given rise to a surge of research into the SARS-CoV-2 virus and other pathogens with pandemic potential. This has been accompanied by the proliferation of new labs to house this work in countries around the world. Although such research can offer significant potential benefits for public health and pandemic preparedness, some experiments can also pose dual-use risks. Additionally, with the extraordinary disruption brought about by COVID-19, terrorist groups and other malicious actors may now understand the catastrophic damage that can be caused by highly transmissible pathogens and other biological agents, and to use them in an attempt to deliberately cause the next pandemic.6 This threat becomes increasingly pressing as rapid, globally distributed technology advances continue to lower the barriers to the synthesis and engineering of pathogens and other biological agents, thereby enabling a wider range of actors to engage in this type of work—including non-state actors.
Governments should play a key role in safeguarding the life sciences against these growing risks, but they have been unable to keep up with rapid advances in technology. According to the 2021 Global Health Security Index, 94 percent of countries have no national-level oversight measures for dual-use research, no agency responsible for such oversight, and no evidence of national assessment of dual-use research.7 At the same time—notwithstanding the important and valuable role of the World Health Organization (WHO)8 and the Biological Weapons Convention9—no international entity has dedicated its primary mission to strengthening biosecurity and bioscience governance, which is critically important for guarding against bioterrorism risks.
NTI has highlighted these global governance gaps through a series of tabletop exercises focused on reducing high-consequence biological threats, which we have convened in partnership with the Munich Security Conference over the past four years.10 Exercise participants have included senior leaders and experts from across Africa, the Americas, Asia, and Europe with extensive experience in public health, biotechnology, and international security. In our reports on these high-level discussions, NTI has shared key findings and offered a number of recommendations for concrete action to counter catastrophic biological threats—ranging from strengthening international capabilities for assessing pandemic origins and improving national-level pandemic preparedness, to developing catalytic financing tools to accelerate pandemic preparedness capacity building and improving bioscience governance globally to guard against emerging biological risks. For example, our 2021 exercise report found that “the international system for governing dual-use biological research is neither prepared to meet today’s security requirements, nor is it ready for significantly expanded challenges in the future. There are risk reduction needs throughout the bioscience research and development life cycle.” To address this gap, NTI recommended establishing an “international entity dedicated to reducing emerging biological risks associated with rapid technology advances,” specifically focused on “reducing the risk of catastrophic events due to accidental misuse or deliberate abuse of bioscience and biotechnology.”11
Preventing Bioweapons Attacks: Constraining Capabilities and Shaping Intent
The full range of work to reduce biological risks posed by non-state actors includes prevention of bioweapons development and use, as well as early detection and effective response, so that biological events can be contained before they grow and spread out of control. Activities across this spectrum can all effectively reduce non-state actor biorisks, but this paper will focus on prevention in particular.
At a basic level, there are two types of approaches to preventing deliberate biological threats: shaping the intent of malicious state or non-state actors and constraining their capabilities. The strategy for combating biological risks posed by non-state actors is different than the approach that is likely to be most effective for preventing development and use of bioweapons by states. One key reason for this is that it is very difficult to shape intent of non-state actors and to deter them from pursuing bioweapons development or use. This is because many non-state actor groups are not motivated by the same rational political, military, and economic goals that motivate most states. As a result, it is unlikely that those responsible for guarding against bioterrorism threats could ever get to a point of high confidence that there are no groups anywhere around the world with the intention of causing large-scale catastrophic damage and who would use biology to do so given the opportunity.
We have to assume that such groups exist now and that they will continue to exist for the foreseeable future. In fact, there is publicly available evidence that such groups have existed in the not-distant past. For example, the Aum Shinrikyo cult, which is widely viewed as an apocalyptic group, pursued the development of chemical and biological weapons in the 1990s and made multiple failed attempts at launching large-scale chemical and biological attacks in Japan.12 We should assume that there are other extremist groups in existence at the moment with similar intentions.
However, while it may be difficult to deter non-state actors, it is more tractable to constrain their capabilities to develop and use bioweapons. That is because non-state actors do not typically have access to the same resources that states do—particularly in terms of trained personnel and financial resources. Therefore, erecting barriers to non-state actor acquisition or development of dangerous pathogens—and increasing their odds of being caught by law enforcement if they do make an attempt—is likely to be one of the most effective ways to counter bioterrorism risks.
To effectively constrain the capabilities of non-state actors, bioscience and biotechnology stakeholders will need to work closely with the biosecurity community to make it more difficult to obtain the know-how, materials, and services needed to acquire or develop dangerous biological agents. This will require more effective safeguards on the global bioscience and biotechnology enterprise to help prevent exploitation.
It is also feasible to increase the chances that a non-state actor group will be detected and get caught by law enforcement in the act of trying to acquire or produce biological agents. As will be discussed later in this article, part of this involves strengthening biothreat intelligence to improve capabilities to detect these types of activities before a bioweapons attack occurs.
Guarding Against Exploitation of Modern Bioscience and Biotechnology
The tools of modern bioscience and biotechnology are increasingly democratized, and access is globally distributed. Importantly, this allows a wide range of communities to access and benefit from these tools. However, this also poses a challenge: how to constrain access of malicious actors to these tools so they cannot be exploited for bioweapons development or use.
The threat reduction strategy should have two key elements:
1. Constraining access to goods and services needed to conduct life science research and development, such as DNA synthesis services, key laboratory reagents, pathogen strains, and some types of equipment.
2. Preventing publication of information that could provide a roadmap that would make it easier for non-state actor groups to engineer or synthesize a dangerous biological agent—for example, by preventing publication of papers that share domain-specific, expert knowledge about how to engineer a pathogen to make it more virulent or transmissible among humans or about how to synthesize dangerous pathogens from scratch.
To help achieve the goals outlined above, there are intervention points throughout the bioscience and biotechnology research and development life-cycle: from project conceptualization and funding, to research execution, and on to publication or commercialization (Figure 1).a
However, with governments unable to keep pace with rapid advances in the life sciences and provide adequate oversight, and without an international organization dedicated to reducing emerging biological risks associated with rapid technology advances, these strategies have not been sufficiently explored or implemented. The world therefore remains vulnerable to exploitation of the legitimate global bioscience and biotechnology enterprise—with potentially catastrophic global consequences.
To address this gap, NTI is working with the World Economic Forum and international partners to develop and launch the International Biosecurity and Biosafety Initiative for Science (IBBIS), an independent organization that will have the mission of working collaboratively with global partners “to strengthen biosecurity norms and develop innovative tools to uphold them. IBBIS will undertake this work to safeguard science and reduce the risk of catastrophic events that could result from deliberate abuse or accidental misuse of bioscience and biotechnology.”13
IBBIS’ initial activities will focus on DNA synthesis screening,b in order to prevent the building blocks of dangerous pathogens from falling into the hands of malicious actors.c However, IBBIS’ scope of activities will expand over time to encompass multiple intervention points throughout the bioscience and biotechnology research and development life-cycle, such as:
- Strengthening and supporting the development of standards for pre-funding biosecurity review by public and private funders of bioscience research and biotechnology development. Funders have significant leverage, and they are well positioned to incentivize incorporation of biosecurity measures into grant or investment proposals.
- Guiding universities and industry in developing effective approaches for strengthening oversight of dual-use bioscience research conducted within their laboratories.
- Partnering with industry to develop biosecurity and biosafety requirements for customers who want access to materials and services to support bioscience research.
- Working with publishers to update their guidelines regarding publication of manuscripts and pre-prints containing information that might be misused.
- Developing proposals for governments to incentivize or require biosecurity practices through funding conditions, regulation, and guidance.
In biosecurity, there is no single solution or intervention that can eliminate all risk. That is why a layered defense is needed, in which multiple interventions in aggregate add up to substantial risk reduction. Furthermore, even if these interventions cannot eliminate all risk, reducing the number of individuals and organizations that have both the capabilities and the intention to carry out a bioweapons attack constitutes a successful risk reduction effort.
Intelligence and Law Enforcement
Catching non-state actors in the act of trying to exploit the legitimate global bioscience and biotechnology enterprise is another way to make risk reduction efforts effective. To achieve this, governments and international organizations need to foster better linkages between law enforcement and efforts by the scientific community to safeguard the life sciences against exploitation.
For example, the United States takes such an approach with DNA synthesis providers, who are asked to report suspicious activity to law enforcement.14 While the bar for such reporting is set quite high and such reports are extremely rare, the underlying idea is that malicious actors should not be able to extensively explore DNA provider systems to see what they can and cannot get away with, without eventually facing negative consequences. If enough red flags add up, the activity should in principle draw the attention of law enforcement. Even if screening is not perfect, if there is a risk of being caught accompanied by unacceptable consequences, that could serve as a powerful deterrent for malicious actors seeking to exploit infrastructure of the legitimate bioscience and biotechnology enterprise.
As noted above, another opportunity for meaningful bioterrorism risk reduction is strengthening biosecurity intelligence capabilities to more effectively detect non-state actors who are seeking to exploit biology to cause harm, so that biological attacks can be prevented before they are attempted. Such an approach would be complementary to the bioscience governance approaches described above, as it would focus on the groups and organizations that may be looking to develop or acquire bioweapons.
Efforts to bolster biothreat intelligence should include investments in both traditional and more modern approaches. First, it would make sense to invest in human intelligence resources that are focused on identifying malicious actors who express interest in exploring bioweapons development and use. This could include dedicating more existing human intelligence resources to this specific issue set, as well as training a cadre of experts with bioscience and biotechnology specific expertise and skills. Second, analysis of publicly available information, including with machine learning-based tools, could be a powerful resource in early identification of emerging biothreats. NTI has demonstrated the efficacy of this approach for preventing nuclear proliferation,15 and similar approaches may be helpful in detecting signals of activity related to bioweapons development or acquisition.
Biosecurity has not been prioritized by the intelligence community in recent years, both in the United States and internationally, and it is an area that needs significantly more investment.
The Path Forward
As bioscience and biotechnology advances continue to progress, within the next 10-20 years radically new possibilities will likely emerge for engineering and synthesizing biological organisms, and these technologies are likely to become very widely distributed.
If the scientific community does not begin to put more effective safeguards in place now, the capability to synthesize or engineer deadly pathogens or other dangerous biological agents could become increasingly widespread, and it could become very difficult to prevent exploitation by terrorist groups seeking to cause harm with biology.
To get ahead of these emerging risks, it will be important to make a more concerted international effort to strengthen global biosecurity norms and to develop practical, effective governance approaches for putting those norms into practice. The WHO has invested significant resources in developing stronger global norms for safeguarding bioscience research,16 and states parties to the Biological Weapons Convention are contemplating adding a Science and Technology Review Mechanism to address emerging biological risks.17 NTI’s work to develop and launch the International Biosecurity and Biosafety Initiative for Science is designed to develop practical tools and governance approaches to put stronger biosecurity norms into practice in countries around the world, which will complement and reinforce existing efforts. Support and engagement with IBBIS when it is launched as a new organization—including by governments, international organizations, the bioscience research community, biotechnology industry, and the philanthropic sector—will be critically important for its success.
As part of international efforts to bolster biosecurity, national governments will need to take steps to strengthen bioscience governance and biosecurity within their respective borders, and NTI’s aspiration is for IBBIS to serve as a resource to support such efforts. As noted above, much of this work will need to focus on more effective safeguards for dual-use bioscience. However, these efforts will also require more effective biosafety and biosecurity measures for high-containment laboratories, as noted by Filippa Lentzos, Gregory Koblentz, and Joseph Rodgers in the first of this two-part series of CTC Sentinel special issues focused on biological threats.18
And as Lawrence Kerr noted in the same issue, “at one point in time, there were 3,000 named apocalyptic groups around the world,” including terrorists “solely interested in annihilation of humans.”19 A comprehensive strategy for preventing such groups from using biology to cause catastrophic harm on a global scale will require investment of significantly more resources in biothreat intelligence and law enforcement capabilities—both in the United States and internationally. These tools will be critically important for early detection of groups looking to carry out a bioweapons attack, so they can be apprehended before they make an attempt.
We must take action now to safeguard the life sciences so society can reap all of their benefits, while guarding against the risks of exploitation and the potential for biotechnology catastrophe caused by terrorist groups or other powerful actors. CTC
Dr. Jaime Yassif serves as Vice President for Global Biological Policy and Programs at the Nuclear Threat Initiative (NTI), where she oversees the program’s work to reduce global biological risks and strengthen biosecurity and pandemic preparedness. Dr. Yassif has 20 years of experience working at the interface of science, technology, and international security—including in philanthropy, government, and non-governmental organizations. Twitter: @JaimeYassif
© 2022 Jaime Yassif
[a] A key goal of engaging publishers to conduct more effective pre-publication biosecurity review is to shift incentives within the scientific community toward adherence to biosecurity best practices. While such an approach may not prevent the sharing of information in other open fora, it could still significantly reduce risks by shifting incentive structures. Many scientists are motivated by the opportunity for a prestigious publication, which can advance their reputation and standing. An open posting that is not followed by a prestigious publication is likely to be less appealing. There are other complementary approaches that could deter scientists from publishing potentially dangerous information in open fora. For example, if there were strong norms against doing so in the community, this could damage their reputation. NTI is exploring the possibility of shaping incentive structures within the scientific community through a “seal of approval” project. See Indira Nath and Jaime Yassif, “Paper 5: Establishing a Seal of Approval to Incentivize Adherence to Biosecurity Norms,” NTI Biosecurity Innovation and Risk Reduction Initiative, October 29, 2018.
[b] “DNA synthesis is a service that is widely used in bioscience research in laboratories around the world,” and it “is critically important for a wide range of biotechnology advances. However, safeguards for DNA synthesis technology … have not kept pace with growing global demand for this service and declining costs.” Most but not all DNA providers screen DNA synthesis orders on a voluntary basis, as it is not legally required by any national government. “To preserve safe and secure global access to DNA synthesis services, NTI is working with the World Economic Forum” and a Technical Consortium of experts “to develop an international Common Mechanism for DNA synthesis screening. This mechanism will be a tool that DNA providers can use to screen DNA synthesis orders” to help ensure that they do not inadvertently sell the building blocks of dangerous pathogens to malicious actors. Jaime M. Yassif, Sarah Carter, and Nicole Wheeler, “Preventing the Misuse of DNA Synthesis Technology,” NTI, n.d.; “NTI and World Economic Forum Release New Report on DNA Synthesis Technologies,” NTI, January 9, 2020.
[c] NTI’s current efforts to bolster DNA synthesis screening are focused on traditional DNA providers, as well as the application of these approaches to benchtop DNA synthesis devices. Next-generation benchtop devices are coming online, which will make it easier to print DNA within one’s own laboratory as opposed to ordering it online from a centralized provider. These newer devices are easier to use than older versions of this technology and, in the coming years, will likely have much better capabilities to produce longer DNA fragments at higher sequence accuracy. It will be important to manage access to these devices—both by screening customers and their orders. This is being actively discussed within the U.S. government and through our work at NTI, and we plan to publish a report on benchtop devices in the coming months.
 “COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU),” Johns Hopkins University & Medicine, Coronavirus Resource Center, n.d.; Chris Alcantara, Youjin Shin, Leslie Shapiro, Adam Taylor, and Armand Emamdjomeh, “Tracking covid-19 cases, deaths and vaccines worldwide,” Washington Post, n.d.; “IMF sees cost of COVID pandemic rising beyond $12.5 trillion estimate,” Reuters, January 20, 2022.
 “Testimony of Jaime M. Yassif, Ph.D., before the U.S. House Foreign Affairs Subcommittee on Asia, the Pacific, Central Asia, and Nonproliferation, hearing on ‘Biosecurity for the Future: Strengthening Deterrence and Detection,” via NTI website, December 8, 2021.
 “Global guidance framework for the responsible use of life sciences” (draft version), World Health Organization, February 22, 2022.
 James Revill, Alisha Anand, and Giacomo Persi Paoli, “Exploring Science and Technology Review Mechanisms under the Biological Weapons Convention,” United Nations Institute for Disarmament Research, June 15, 2021.
 “NTI and Munich Security Conference Convene Global Leaders for Fourth Annual Tabletop Exercise on Reducing High-Consequence Biological Threats,” NTI, February 23, 2022; “NTI|Bio, Munich Security Conference Convene Global Leaders for Annual Tabletop Exercise on Reducing High-Consequence Biological Threats,” NTI, March 18, 2021.
 Jaime M. Yassif, Kevin P. O’Prey, and Christopher R. Isaac, “Strengthening Global Systems to Prevent and Respond to High Consequence Biological Threats: Results from the 2021 Tabletop Exercise Conducted in Partnership with the Munich Security Conference,” NTI Paper, November 2021; Beth Cameron, Jaime Yassif, Jacob Jordan, and Jacob Eckles, “Preventing Global Catastrophic Biological Risks: Lessons and Recommendations from a Tabletop Exercise Held at the 2020 Munich Security Conference,” Open Philanthropy Project, 2020.
 Hidemi Yuki, Lloyd Hough, Marc Sageman, Richard Danzig, Rui Kotani, and Terrance Leighton, “Aum Shinrikyo: Insights Into How Terrorists Develop Biological and Chemical Weapons,” Center for a New American Security, July 20, 2011; Richard Danzig and Zachary Hosford, “Aum Shinrikyo – Second Edition – English,” Center for a New American Security, December 20, 2012.
 “Global Biosecurity Organization Executive Director, Global Biological Policy and Programs (NTI | bio),” NTI, n.d.
 Diane DiEuliis, Sarah R. Carter, and Gigi Kwik Gronvall, “Options for Synthetic DNA Order Screening, Revisited,” mSphere 2:4 (2017); “On Guard Against WMD Inside the Biological Countermeasures Unit, Part 2,” FBI, February 24, 2012.
 Jason Arterburn, Erin D. Dumbacher, and Page O. Stoutland, “Signals in the Noise: Preventing Nuclear Proliferations with Machine Learning & Publicly Available Information,” C4ADs and NTI, 2021.
 “Global guidance framework for the responsible use of life sciences.”
 James Revill, Alisha Anand, and Giacomo Persi Paoli, “Exploring Science and Technology Review Mechanisms under the Biological Weapons Convention,” United Nations Institute for Disarmament Research, June 15, 2021.
 Paul Cruickshank, Don Rassler, and Kristina Hummel, “A View from the CT Foxhole: Lawrence Kerr, Former Director, Office of Pandemics and Emerging Threats, Office of Global Affairs, U.S. Department of Health and Human Services,” CTC Sentinel 15:4 (2022).