Abstract: The biological risk landscape is rapidly evolving and presents significant new challenges to preventing the accidental, reckless, or malicious misuse of biology. At the same time, oversight systems to ensure that life sciences research is conducted safely, securely, and responsibly are falling behind. An urgent overhaul to realign biorisk management with contemporary risks is needed. This must include not only an international framework to establish values and principles for biorisk management and guidelines to develop and implement governance tools and mechanisms, but also an authoritative international institution with a mandate to systematically register and track maximum containment facilities and to oversee extremely high-risk research.
The origin of COVID-19 is hotly debated and heavily politicized. It is possible that the virus naturally spilled over from animals to humans. Another theory is that the virus escaped from a lab, most likely the Wuhan Institute of Virology, or that scientists were infected when doing fieldwork with bats. There may never be a credible international investigation into the origins of COVID-19.
Yet, regardless of what sparked the pandemic, what is known is that accidents happen and that dangerous viruses can escape from labs around the world. And the risks of this happening are increasing. Ironically, greater efforts to prevent future pandemics and to strengthen biopreparedness—by prospecting for dangerous viruses in animals or engineering viruses in the lab to anticipate and better understand dangerous viruses that could emerge from nature—could actually lead to increased risks of accidental or deliberate pandemics. The answer is simple. The international community needs to strengthen local and global biorisk management. The hard part is making this happen in practice.
This article first examines the evolving biorisk landscape, before evaluating the woefully insufficient international and national efforts at biorisk management. The final section provides recommendations for strengthening global biorisk governance.
Increasing Biological Risks
Globally, there are now around 60 maximum containment laboratories, commonly referred to as biosafety level 4 (BSL-4) labs, that are designed to work safely and securely with pathogens that cause life-threatening diseases and for which there are limited or no vaccines or treatments.a BSL-4 labs work with the most dangerous pathogens such as smallpox, Ebola, Marburg, and Lassa fever. Half of the labs for which dates of establishment are available began operating in the last 10 years.1 They are spread over 23 countries. About half of them are in Europe. Most of them are in big cities. Before the pandemic, China completed two BSL-4 labs, and it has signaled that it intends to follow through with plans to build up to five more.2 Since the beginning of the pandemic, five countries have announced plans to build 19 new BSL-4 labs, including 15 labs in Russia,3 one in the Philippines,4 one in Taiwan,5 one in India,6 and one in the United States.7 While BSL-4 labs take several years to design, build, and commission, one can expect that as these new labs come online, the risk of accidents will increase.
But it is not simply more labs that increase biosafety risks. There is also an upward trend in high-risk research. Creating dangerous viruses has regularly occurred in labs. In 2005, for example, scientists recreated the 1918 influenza virus that had led to the deadliest pandemic of the 20th century.8 In 2011, scientists manipulated the bird flu virus to enable it to transmit between mammals, including humans.9 Before then, the virus had only been transmitted from birds to humans, with a fatality rate of 30-60 percent.10 In comparison, COVID-19 has a fatality rate of approximately two to three percent.11 In 2018, scientists announced they had created horsepox, a close cousin of smallpox, from chemically synthesized DNA fragments.12 This research highlighted some of the dangers of synthetic biology. David Evans, who led the synthetic horsepox project, stated, “Have I increased that risk? I don’t know. Maybe yes, but in reality, that risk has always been there.”13
The COVID-19 pandemic will likely increase the number of laboratories and scientists creating novel, ‘chimeric’ viruses that combine the genes of two or more strains. The colloquial term used to describe the creation of these engineered viruses is ‘gain-of-function’ research since the resulting, lab-made strain of the virus may have enhanced virulence or transmissibility compared to the naturally occurring version. This research is used to characterize the potential for newly discovered viruses to cause pandemics by providing a better understanding of how easily these viruses can infect human cells, which is indicative of the potential for the virus to jump from animals to humans and to spread human-to-human.14 There was a significant increase in this type of research by influenza virologists following the 2005 H5N1 and 2009 H1N1 outbreaks.15 There has been a dramatic surge in scientific publications about SARS-CoV-2, the virus that causes COVID-19, and related coronaviruses over the last two years.16 It also appears that a lab in the United States has been interested in adding genetic material from the original SARS virus, which first emerged in 2003, to the COVID-19 strain to create an aggressive chimeric virus of the two strains.17
Research activities outside of labs are also increasing biosafety risks. The current pandemic will likely increase large-scale viral prospecting, which involves collecting biomedical samples from wild animals to identify potential pandemic pathogens.18 For example, in 2021, USAID announced a five-year, $125 million viral characterization program called Discovery & Exploration of Emerging Pathogens – Viral Zoonoses (DEEP VZN), which is expected to identify 8,000-12,000 new viruses and characterize the risk they pose of causing a pandemic.19 Chinese researchers have also called for more field research to improve their ability to predict the risk of zoonotic spillover events.20 The emergence of SARS, MERS, and SARS-CoV-2 has already demonstrated that such viruses are currently circulating in animals and can jump to humans and spread internationally under the right conditions. Actively searching for these viruses will increase the risk of infection in the field by a novel and potentially pandemic-capable virus. Yet, standards for field biosafety are much less developed than for laboratory biosafety. Neither the United States nor China, for example, have national field biosafety standards, and there is no international guidance available on this subject. Similarly, the increasing use of mobile laboratories, while very helpful in containing outbreaks, may also increase the risk of accidental or deliberate contamination. Many of these labs were constructed and deployed by the international community to respond to the 2014-2016 Ebola epidemics in Africa.21 While these labs are largely for diagnostic purposes, projects such as the European Mobile Laboratory Project work with risk group 4 pathogens in mobile lab conditions.22 This diagnostic capability is important when responding to emerging biological threats, but the trade-off between safety and mobility also introduces new areas of risk that need to be examined in greater detail.
Increasing Concerns over Security and Dual-Use
The increase in laboratories and scientists working on dangerous pathogens has created more opportunities for these agents to be stolen, particularly by insiders. Historically, laboratories and culture collections have been the preferred source of pathogens for terrorists and criminals. There is no evidence that any terrorist or criminal group has successfully acquired a pathogenic microorganism from nature.b Aum Shinrikyo, for example, was only able to acquire a harmless vaccine strain of anthrax.23 The increased number of individuals with expertise in and access to dangerous pathogens also poses increased security risks. According to the Federal Bureau of Investigation, Bruce Ivins, a scientist at the U.S. Army Military Research Institute of Infectious Diseases (USAMRIID), the U.S. military’s premier biodefense facility, was the sole perpetrator of the 2001 anthrax letter attacks in the United States that sickened 17 and killed five.24
A different type of security risk is that the knowledge and methods used to understand and manipulate the biological and epidemiological properties of pathogens for public health purposes is repurposed to cause harm. Advances in science have the potential to provide new knowledge and tools to national militaries, international terrorist networks, criminal groups, religious extremists, disgruntled or mentally ill scientists, or even ill-intentioned ‘biohackers’—do-it-yourself biologists who are not necessarily motivated by politics or religion, but possibly by curiosity, revenge, greed, or boredom. Biodefense research on dangerous pathogens is especially susceptible to this ‘dual-use dilemma’ since it is frequently focused on studying characteristics such as infectivity (ability of a microorganism to infect a host), pathogenicity (ability of a microorganism to cause disease), virulence (severity of the disease caused by the organism), and transmissibility (ability of the pathogen to spread from person to person).
The biosecurity landscape has also been altered by changes in how scientific research is disseminated. The emergence of pre-print servers, where scientists can post their findings before going through the peer review process, has removed one of the layers of review that could be used to check for dual-use research of concern before the dissemination of the research. The urgency of responding to the pandemic led to a dramatic rise in the use of pre-print servers. During the first nine months of the pandemic, half of all scientific publications on SARS-CoV-2 were posted to pre-print servers.25 In contrast, during previous outbreaks, only five percent of scientific research was disseminated this way.26 In addition, the rise of the open science movement, which seeks to make protocols, datasets, and computational tools as widely available as possible, has introduced new potential risks of misuse.27 For example, the publication of a detailed protocol for how to synthesize SARS-CoV-2, the virus responsible for COVID-19, has raised concerns that such protocols have lowered the barrier to creating engineered versions of the virus.28
Important developments taking place in fields of the life sciences other than microbiology and molecular biology, such as immunology, population genomics, gene therapy, viral vectors, genome editing, gene drives, synthetic biology, and neuroscience, are not covered by existing biosecurity and dual-use research policies.29 These policies also do not sufficiently take into account how security and dual-use risks can be generated by the convergence of multiple disciplines within the life sciences or by the application of emerging technologies, such as machine learning, artificial intelligence, data analytics, and nanotechnology, to the life sciences.30 Overall, these scientific and technical advances have created new potential attack vectors and the means for rapidly identifying novel ones. Many of these new attack vectors do not involve actual pathogens, but instead relate to genetic constructs and associated means of delivery such as viral vectors and lipid nanoparticles.31 For example, the National Academies of Science has identified dual-use risks posed by the manipulation of the human immune system and microbiome, which can be accomplished with CRISPR genome editors delivered by viral vectors.32
High-risk pathogen research congruently poses challenges to peace and international security. While biodefense activities such as the development of protective gear, medical countermeasures, and detection and diagnostic systems are justifiable, the proliferation of laboratories and research institutions handling dangerous pathogens may instill a fear of the weaponization of biology among the public or policymakers. In turn, this heightened perception that biological weapons are an increasing threat may provide the justification for a country to initiate or expand an offensive biological warfare program.33 One particularly sensitive research area is related to threat assessment, which involves research on pathogens to characterize their potential utility as biological weapons. While such research can be used to inform the development of medical countermeasures and other biodefenses, it can also generate knowledge potentially useful for offensive biological weapons applications.34
on the island of Riems, Germany, on July 2, 2020. (Jens Büttner/picture alliance via Getty Images)
Insufficient Biorisk Management
Traditionally, biosafety, which is designed to prevent the accidental release of a pathogen from a lab, has gained more attention than biosecurity, which is designed to prevent the malicious misuse of pathogens and biotechnology, and dual-use research, but all must be better governed. The umbrella term ‘biorisk management’ is an overarching framework to discuss the full spectrum of risks associated with the life sciences enterprise. A biorisk is a risk that a biological event—such as a naturally occurring disease, an accidental infection, an unexpected discovery, an unauthorized access, loss, theft, misuse, diversion, or intentional release of a biological agent or biological material—adversely affects the health of humans, non-human animals, or the environment. Approaching the domains of biosafety, biosecurity, and oversight of dual-use research collectively under the rubric of biorisk management has the advantage of recognizing and capitalizing on how they are interconnected without sacrificing the specific demands, challenges, and risks that each presents. Yet biorisk management has significant gaps and weaknesses globally.35
A 2021 survey of biorisk management policies around the world found that most countries do not have comprehensive, or ‘whole-of-government,’ systems for biosafety and biosecurity, and that virtually none have national policies regulating dual-use life science research.36 Only six countries, or one-quarter of the 23 countries with maximum containment laboratories, were scored as having high levels of biosafety and biosecurity. Only five of these 23 countries had policies on dual-use research. This means that a large majority of countries with BSL-4 labs do not have specific oversight of ‘gain-of-function’ research on potential pandemic pathogens that has been a central feature in the debate on COVID-19’s origin.37
Even countries such as the United States that scored high on biosecurity and biosafety have demonstrated less than stellar implementation of those policies in practice, as exemplified by questionable oversight of ‘gain-of-function’ research funded by the National Institutes of Health (NIH).38 As revealed by documents obtained through FOIA requests, NIH did not submit proposed research that could be reasonably anticipated to enhance the virulence or transmissibility of a potential pandemic pathogen for review by the Department of Health and Human Services (HHS) as required under HHS’ 2017 Potential Pandemic Pathogen Care and Oversight (P3CO) policy.39 NIH reportedly funded at least eight projects since 2017 that appear to have involved ‘gain of function’ research, but only forwarded three of these projects to HHS for review under the P3CO policy.40
Among the few countries that do have biosecurity and dual-use oversight policies, they are usually focused on the potential misuse of a short list of specific pathogens such as those that cause anthrax, plague, Ebola, and smallpox. Aside from the microbiology and molecular biology communities that work with these listed pathogens, called ‘select agents’ in the United States, awareness of biorisk management principles and practices in the wider scientific community is limited.41 And, each of these areas—biosafety, biosecurity, and dual-use research—is typically stove-piped within multiple government agencies, which results in fragmented oversight. In some countries, such as the United States, oversight of dual-use research is almost entirely limited to institutions and individuals in receipt of government funds and conducting experiments on select agents. A private company that does not receive federal funding for life sciences research can modify a select agent (with a few minor exceptions), or other pathogens not included in that list, with no obligation to review the research for potential dual-use implications or seek approval from a government agency before conducting the research. This means that almost all dual-use research based on non-government sources of funding—such as from corporations, foundations, wealthy individuals, and crowdfunding sites, which is increasingly driving the innovation process in the life sciences—is not covered. For the first time, federal funding in the United States accounted for less than 50 percent of national spending on scientific research in 2013.42 In 2015, more Ph.D. researchers in the United States were employed in the private sector than in academia, including 40 percent of those in the life sciences.43 The risks posed by privately funded research is illustrated by the aforementioned synthesis of the horsepox virus, which was financed by an American biotech company for only $100,000.44 In 2021, synthetic biology companies raised nearly $18 billion, almost as much as the total investment that the industry had received since 2009.45 Given the increasing size of the global bioeconomy and the growing commercialization of products generated with synthetic biology and genome editing tools, the exclusion of almost all of the work of the private sector from dual-use research oversight is an increasingly large loophole.
At the international level, there is no body that standardizes principles for biosafety, biosecurity, and dual-use research oversight and monitors compliance with these standards. As the spread of the original SARS-CoV-2 virus and its subsequent variants has demonstrated, global health is only as strong as its weakest link. A failure in biosafety or biosecurity anywhere in the world could have repercussions around the globe.
Recommendations for Strengthening Global Biorisk Governance
Given the increasing number of countries developing dual-use biotechnologies and conducting risky research with pathogens, the transnational nature of modern life sciences research, and the potential global impact of an accidental or deliberate release of a pandemic-capable pathogen, international mechanisms for ensuring that this research is being conducted safely, securely, and responsibly are crucial.
At the lab-level, institutions must work to cultivate a culture of biosafety, biosecurity, and responsible research with high-risk pathogens. This does not just apply to BSL-4 labs; lower-containment level labs should also be nurturing a culture of safe, secure, and responsible working practices. This should encompass all levels, from students and technicians to principal investigators to laboratory directors. It is also important to stress that developing a culture of safe, secure, and responsible working practices is not a one-off event, but a continual effort.46
At the national level, all countries, but particularly countries where high-risk pathogen work is conducted, should have laws and regulations in place that maintain oversight of BSL-4 labs, and that require comprehensive risk assessments of proposed research for safety, security, and dual-use activities with significant potential to be repurposed to cause harm. In addition to laws and regulations, countries and the BSL-4 labs within them should also implement and share best practices, and participate in peer reviews of practices in other BSL-4 labs. Countries with experience in designing and operating high-containment laboratories should share their expertise in building risk-based laboratory infrastructure that is fit for purpose, is safe and secure, and can be maintained over the long-term. Countries with BSL-4 facilities must also provide complete, regular, and transparent reporting under the annual confidence-building measures of the Biological Weapons Convention and under U.N. Security Council Resolution 1540. While most countries with BSL-4 facilities generally submit these documents, there is no international requirement mandating this information. The information should also be made publicly available by all countries. So far, for example, only nine of the 22 countries that report their BSL-4 labs under the confidence-building measures of the BWC make these reports public. Only 55 percent of the BSL-4 labs in operation provide links to their publications on their institutional websites.47 Making BWC and 1540 reporting publicly available should not be a difficult task since the existence of these facilities is not secret and nearly every BSL-4 laboratory has a website. This measure would strengthen international transparency and confidence, and would assist in further research to strengthen global biological lab governance.
At the international level, frameworks establishing values and principles for biorisk management and guidelines for developing and implementing governance tools and mechanisms should be developed. In addition, an authoritative international institution with a mandate to systematically register and track maximum containment facilities and to oversee extremely high-risk research should be put in place to ensure all such research is being conducted safely, securely, and responsibly. One relatively easy way to do this would be for all BSL-4 labs and those engaged in gain-of-function research with potentially pandemic pathogens to adopt the ISO 35001 standard on “biorisk management for laboratories and other related organisations.” Created by the International Organization for Standardization (ISO) in 2019, ISO 35001 is an international standard for a biorisk management system. The system is ready for use by laboratories and provides recommendations for laboratory leadership, planning, support, operation, performance evaluation, and how to implement improvement in an iterative manner.48 The system could also be used by lower-containment level labs to strengthen their culture of biosafety and security. The standard uses third-party validation, and to maximize the potential of ISO 35001, there needs to be an international structure to ensure compliance. While national regulators could act as the third-party, this would have limited credibility internationally, especially for jurisdictions without proven track records for transparency and accountability. One alternative would be to build out the current International Experts Group of Biosafety and Biosecurity Regulators to take on the role.49 Another would be to mandate the World Health Organization to make it directly responsible, in much the same way that it conducts biennial biosafety and biosecurity inspections of the variola virus depositories in the United States and Russia.50
Lastly, while these structural and policy steps should be taken to reduce biological risks, it is crucial that the life sciences continue to develop and maintain a culture of biosafety, biosecurity, and responsible conduct. To support this process, the World Health Organization should establish regional collaborating centers on biorisk management to conduct education and training, provide forums for exchanging best practices, and support organizations and activities that foster cultures of safety, security, and responsibility within the life sciences.
The development of medical countermeasures in record time to prevent and treat COVID-19, which built on decades of studying coronaviruses and developing advanced biotechnologies, demonstrated the importance of a robust biomedical research enterprise for pandemic response. While the benefits of such research are undeniable, it is also clear that this research poses safety, security, and dual-use risks. In a worst-case scenario, research intended to prevent the next pandemic could cause one by accident or through reckless or malicious misuse of biotechnology. Unfortunately, the current national and international systems to ensure that life sciences research is conducted safely, securely, and responsibly is already inadequate. A major overhaul of global biorisk management is needed to ensure that humanity’s efforts to limit the scourge of infectious disease do not inadvertently make the problem worse. CTC
Filippa Lentzos is a Senior Lecturer in the Department of War Studies and Co-Director of the Centre for Science and Security Studies at King’s College London. She is also an Associate Senior Researcher at the Stockholm International Peace Research Institute (SIPRI) and a Non-Resident Scholar at the James Martin Center for Nonproliferation Studies (CNS). Twitter: @FilippaLentzos
Gregory D. Koblentz is Associate Professor and Director of the Biodefense Graduate Program at the Schar School of Policy and Government at George Mason University. He is also a member of the Scientists Working Group on Biological and Chemical Security at the Center for Arms Control and Non-Proliferation. Twitter: @gregkoblentz
Joseph Rodgers is a Program Manager and Research Associate with the project on nuclear issues at the Center for Strategic and International Studies (CSIS). He is also a Ph.D. student in the biodefense program at George Mason University and a Visiting Research Associate in the Department of War Studies at King’s College London. Twitter: @NonproJoe
© 2022 Filippa Lentzos, Gregory D. Koblentz, Joseph Rodgers
Substantive Notes
[a] Laboratories that work with infectious agents and toxins are categorized by their level of necessary safety measures with BSL-1 being the lowest and BSL-4 being the highest. BSL-4 labs are equipped with positive pressure suits or biosafety cabinets to prevent the infection of researchers as well as HEPA filters and effluent treatment systems to prevent the escape of a pathogen from the lab. In addition, these engineering controls are supplemented by policies and procedures to reduce the chance of an accidental infection or environmental release. World Health Organization, Laboratory Biosafety Manual, Fourth Edition (Geneva: World Health Organization, 2020), pp. 59-64.
[b] W. Seth Carus, Bioterrorism and Biocrimes: The Illicit Use of Biological Agents since 1900 (Washington, D.C.: National Defense University, 2001), p. 8. While this source is dated, this finding is supported by more recent research. According to Markus Binder, architect of the National Consortium for the Study of Terrorism and Response to Terrorism’s POICN database, which is comprised of 517 CBRN-related incidents between 1990 and 2016, “There don’t appear to have been any efforts, at least not publicly revealed, to obtain bio-agents from nature and then use the isolated agent to produce a significant quantity of agent for use in an attack.” Author (Koblentz) email communication, Markus Binder, April 2022.
Citations
[1] Filippa Lentzos and Gregory D. Koblentz, Mapping Maximum Biological Containment Labs Globally (London: King’s College London, May 2021).
[2] Yuan Zhiming, “Current status and future challenges of high-level biosafety laboratories in China,” Journal of Biosafety and Biosecurity 1 (2019); Frank Chen, “China goes on biosafety lab building spree,” Asia Times, July 7, 2020.
[3] “Russia to set up 15 highest biosafety level labs by 2024 —watchdog chief,” TASS, August 17, 2021.
[4] Cathrine Gonzales, “PH’s Virology Institute to rise in end-2023 or in 2024 — DOST,” Inquirer, May 25, 2021.
[5] Lin Chia-nan, “Defense medical center to build NT$900m laboratory,” Taipei Times, August 26, 2021.
[6] “DRDE to set up advanced biological defence lab in Gwalior to research, fight dangerous viruses,” Economic Times, December 18, 2021.
[7] “Congressional Justification of the NIH Request for the Fiscal Year (FY) 2023 Budget,” National Institutes of Health, March 28, 2022.
[8] Jeffery K. Taubenberger, Ann H. Reid, Raina M. Lourens, Ruixue Wang, Guozhong Jin, and Thomas G. Fanning, “Characterization of the 1918 influenza virus polymerase genes,” Nature 437 (2005); Terrence M. Tumpey et al., “Characterization of the reconstructed 1918 Spanish influenza pandemic virus,” Science 310 (2005).
[9] Sander Herfst et al., “Airborne transmission of influenza A/H5N1 virus between ferrets,” Science 336 (2012); Masaki Imai et al., “Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets,” Nature 486 (2012).
[12] Ryan S. Noyce, Seth Lederman, and David H. Evans, “Construction of an infectious horsepox virus vaccine from chemically synthesized DNA fragments,” PLOS One 13:1 (2018).
[15] Lynn Klotz, Minimum Estimate of Number of Laboratories in the Influenza PPP Research Enterprise (Washington, D.C.: Center for Arms Control and Non-Proliferation, 2019).
[16] Sriharshita Musunuri, Jonas B. Sandbrink, Joshua T. Monrad, Megan J. Palmer, and Gregory D. Koblentz, “Rapid proliferation of pandemic research: implications for dual-use risks,” mBio 12 (2021).
[18] Sandbrink, Ahuja, Swett, Koblentz, and Standley.
[20] Tian Qin, Xiangdong Ruan, Zhaojun Duan, Jianping Cao, Junrong Liang, Jing Yang, Yan Jiang, Mang Shi, and Jianguo Xu, “Wildlife-borne microorganisms and strategies to prevent and control emerging infectious diseases,” Journal of Biosafety and Biosecurity 3 (2021).
[21] Roman Wölfel et al., “Mobile diagnostics in outbreak response, not only for Ebola, A blueprint for a modular and robust field laboratory,” European Surveillance 20:44 (2015).
[22] “European Mobile Laboratory Project,” European Union, 2012-2016.
[23] Gregory D. Koblentz, Living Weapons: Biological Warfare and International Security (Ithaca: Cornell University Press, 2009), pp. 212-213.
[24] Ibid., pp. 205-212.
[25] Panpan Wang and Deqiao Tian, “Bibliometric Analysis of Global Scientific Research on COVID-19,” Journal of Biosafety and Biosecurity 3 (2021).
[26] Ibid.
[27] James A. Smith and Jonas Sandbrink, “Open Science Practices and Risks Arising from Misuse of Biological Research,” MetaArXiv, December 10, 2021.
[28] Jaspreet Pannu, Jonas B. Sandbrink, Matthew Watson, Megan J. Palmer, and David A. Relman, “Protocols and risks: when less is more,” Nature Protocols 17 (2022); Rebecca Mackelprang et al., “Making Security Viral: Shifting Engineering Biology Culture and Publishing,” ACS Synth. Biol. 11:2 (2022).
[29] Filippa Lentzos, Edward P. Rybicki, Margret Engelhard, Pauline Paterson, Wayne Arthur Sandholtz, and R. Guy Reeves, “Eroding norms over release of self-spreading viruses,” Science 375:6,576 (2022): pp. 31-33; Jonas Sandbrink and Gregory D. Koblentz, “Biosecurity Risks Associated with Vaccine Platform Technologies,” Vaccine, February 25, 2021; Gregory D. Koblentz, “The De Novo Synthesis of Horsepox Virus: Implications for Biosecurity and Recommendations for Preventing the Reemergence of Smallpox,” Health Security 15:5 (2017); Kyle E. Watters, Jesse Kirkpatrick, Megan J. Palmer, and Gregory D. Koblentz, “The CRISPR Revolution and its Potential Impact on Global Health Security,” Pathogens and Global Health 115:2 (2021); Robert Bruner and Filippa Lentzos, “Militarising the Mind: Assessing the Weapons of the Ultimate Battlefield,” BioSocieties 14:1 (2018): pp. 94-122; Kenza Samlali, Julie Stern, and Elicana Nduhuura, “Towards Responsible Genomic Surveillance: A Review of Biosecurity and Dual-use Regulation,” 2021 Next Generation for Biosecurity Competition, November 8, 2021; Filippa Lentzos, “How to protect the world from ultra-targeted biological weapons,” Bulletin of Atomic Scientists 76:6 (2020): pp. 302-308.
[30] Emerging Technologies and Dual-use Concerns: A Horizon Scan for Global Public Health (Geneva: World Health Organization, 2021).
[31] Ibid., pp. 7-8.
[32] National Academies of Sciences, Engineering, and Medicine, Biodefense in the Age of Synthetic Biology (Washington, D.C.: National Academies Press, 2018).
[33] Gregory Koblentz and Filippa Lentzos, “21st Century Biodefence: Risks, Trade-offs, and Responsible Science,” BWC Review Conference Series Paper No. 3 (Oslo: International Law and Policy Institute, 2016); Filippa Lentzos and Jez Littlewood, “DARPA’s Prepare program: Preparing for what?” Bulletin of Atomic Scientists, July 26, 2018; Filippa Lentzos, “How do we control dangerous biological research?” Bulletin of Atomic Scientists, April 12, 2018; Dual Use Research of Concern in the Life Sciences: Current Issues and Controversies (Washington, D.C.: National Academies of Science, Engineering, and Medicine, 2017); Christian Enemark, Biosecurity Dilemmas: Dreaded Diseases, Ethical Responses, and the Health of Nations (Washington, D.C.: Georgetown University Press, 2017).
[34] Gregory D. Koblentz, “Quandaries in Contemporary Biodefense Research,” in Filippa Lentzos ed., Biological Threats in the 21st Century (London: Imperial College Press, 2016), pp. 314-318.
[35] Lentzos, Rybicki, Engelhard, Paterson, Sandholtz, and Reeves; Sandbrink and Koblentz; Koblentz, “The De Novo Synthesis of Horsepox Virus;” Watters, Kirkpatrick, Palmer, and Koblentz; Bruner and Lentzos; Samlali, Stern, and Nduhuura; Lentzos, “How to protect the world from ultra-targeted biological weapons.”
[36] Jessica A. Bell and Jennifer B. Nuzzo, “2021 Global Health Security Index: Advancing Collective Action and Accountability amid Global Crisis,” December 2021.
[37] Lentzos and Koblentz, Mapping Maximum Biological Containment Labs Globally.
[38] Gregory D. Koblentz and Lynn C. Klotz, “New Pathogen Research Rules: Gain of Function, Loss of Clarity,” Bulletin of the Atomic Scientists, February 26, 2018; Jocelyn Kaiser, “NIH says grantee failed to report experiment in Wuhan that created a bat virus that made mice sicker,” Science, October 21, 2021.
[39] Mara Hvistendhal and Sharon Lerner, “FBI Sought Documents Related to US Funded Coronavirus Research in China,” Intercept, January 20, 2022; Mara Hvistendhal and Sharon Lerner, “NIH Officials Worked with Ecohealth Alliance to Evade Restrictions on Coronavirus Experiments,” Intercept, January 20, 2022.
[40] David Willman and Madison Muller, “A science in the shadows,” Washington Post, August 26, 2021.
[41] Global guidance framework for the responsible use of life sciences: Mitigating biorisks and governing dual-use research (Geneva, Switzerland: World Health Organization, 2022).
[44] Gregory D. Koblentz, “A Critical Analysis of the Scientific and Commercial Rationales for the Synthesis of Horsepox Virus,” mSphere 3:2 (2018): pp. 1-10.
[45] Mark Bünger and Larry Upton, “4Q 2021 Synthetic Biology Venture Investment Report,” Built with Biology, February 9, 2022.
[46] Dana Perkins, Kathleen Danskin, A. Elise Rowe, and Alicia A. Livinski, “The Culture of Biosafety, Biosecurity, and Responsible Conduct in the Life Sciences: A Comprehensive Literature Review,” Applied Biosafety 23:4 (2018): pp. 1-12.
[47] Lentzos and Koblentz, Mapping Maximum Biological Containment Labs Globally.
[48] “ISO 35001:2019 Biorisk management for laboratories and other related organisations,” International Standards Organization, November 2019.
[50] Jonathan B. Tucker, “Preventing the Misuse of Biology: Lessons from the Oversight of Smallpox Virus Research,” International Security 31:2 (2006): pp. 116-150. See also the WHO’s most recent inspection report of the CDC in the United States and of VECTOR in Russia: “Report of the World Health Organization (WHO) biosafety inspection team of the variola virus maximum containment laboratories to the centers for disease control and prevention (CDC), Atlanta, Georgia, United States of America, 20-24 May 2019,” World Health Organization, 2019; “Report of the World Health Organization (WHO) biosafety inspection team of the variola virus maximum containment laboratories to the state research centre of virology and biotechnology (’SRC VB VECTOR’), Koltsovo, Novosibirsk Oblast, Russian Federation, 28 January- 2 February 2019,” World Health Organization, 2019.
