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Introduction

Building on the National Academies of Sciences, Engineering, and Medicine’s decades of work addressing various issues related to countering biological threats domestically and internationally, an ad hoc planning committee conducted four workshops on Biological Threats in the Age of Emerging Biotechnology.¹ An international committee of experts from relevant academic, government, and private sector entities identified specific research areas and technologies to use as case studies during the virtual workshops to understand and evaluate existing frameworks for assessing risks and benefits and to explore potential needs for such assessments. These experts include representatives from countries engaged in the workshops (India, Peru, Mexico, and Argentina) and with expertise across a variety of life science disciplines (e.g., synthetic biology, microbiology, molecular biology, genetics), associated disciplines (e.g., bioengineering, computational biology), risk and benefit assessment, and biological security. They planned, spoke during, and moderated discussions to provide insights on emerging biotechnology and potential risks, and frameworks for mitigating those risks while enabling responsible research. The workshops were held in several stages. An introductory framework was conducted on December 10, 2024 and three case-study-based workshops were held on September 10, 17, and 18, 2025.

The project focused on strengthening the ability of academic and industry scientists to recognize and safeguard research from deliberate use for harm, accidents, and

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¹ This proceedings has been prepared by the workshop rapporteur as a factual summary of what occurred at the workshop. The planning committee’s role was limited to planning and convening the workshop. The views contained in the proceedings are those of individual workshop participants and do not necessarily represent the views of all workshop participants, the planning committee, or the National Academies of Sciences, Engineering, and Medicine.

unauthorized access to knowledge, technologies, and data, and in partnering with international experts to advance these efforts. The workshop series engaged U.S. and international scientists from India, Peru, Mexico, and Argentina in identifying, assessing, and mitigating risks and vulnerabilities about biotechnology and/or life-science-specific advances and data, while ensuring scientific progress and benefits can be realized. These countries provide new opportunities for expanding the discourse about safeguarding biotechnology research and development from misuse or unauthorized access and use by malicious actors. The workshops also aimed to describe best practices for protecting biological data and knowledge from unauthorized access and transfer while also promoting the sharing of these scientific data. Although biotechnologies are developed for and used in research for many different issues–health, agriculture, industry, and others–much of the current biosecurity and biosafety policies and risk assessment frameworks focus on applications of biotechnologies with pathogens and toxins rather than other applications, though they may be associated with security and safety risks. This workshop series sought to understand relevance of these and related security policies and frameworks for assessing applications of biotechnologies that do not involve pathogens and toxins, and additional information that may be needed to assess risks and benefits of these biotechnology applications. The committee adopted a scenario or case-study-based approach to provide participants with an opportunity to focus their discussions about organization, governance, and risk and benefit assessment and mitigation on specific examples, rather than generic conversation. The committee’s goal was to elicit cross-national comparative attention to regulatory processes, gain insights from researchers and private sector organizations, and pose questions about where (and how) risk-assessment and mitigation responsibilities and policies may be structured.

The committee planned the four-part series with intention, starting with introducing the history of dual-use policies and understanding how global and country-specific policies and guidelines evolved over time. The committee structured the remaining workshops to focus discussions around specific case studies, allowing participants to discuss how these policies apply to the specific examples and what still is needed to assess risk and benefit and identify strategies for reducing risk. These discussions were designed to prompt thoughtful consideration of risk and benefit assessment frameworks that may be applied to other biotechnologies, in addition to the ones highlighted by the scenarios. This proceedings summarizes the main points discussed during the workshop.

PROJECT STATEMENT OF TASK AND PLANNING COMMITTEE APPROACH

With the background of the project request from the sponsor, the planning committee reviewed the statement of task and developed an approach to the four workshop meetings.

Committee Approach

The planning committee addressed the statement of task (see Box 1-1) in a four-part meeting series. The first meeting focused on establishing committee definitions for the project and reviewing existing frameworks that govern biotechnology research and development (see Box 1-2). To help guide the discussions around identifying, assessing, and mitigating the risks that arise when life sciences intersect with other disciplines to create new biotechnologies, a case-study approach was used to highlight complexities in different biotechnology areas (see Appendix B), to have more specific observations on framework gaps and opportunities.

Committee Definitions

The planning committee compared many definitions from biosecurity and biotechnology development perspectives to help define terms relevant to this project. Box 1-2 provides the definitions used by the planning committee for key concepts guiding the

workshop discussions. Workshop Planning Committee co-chair Maria Espona, ArgIQ, noted the importance of assessing both risks and benefits, given that developing emerging biotechnologies and their products are intended to be beneficial.

DUAL-USE CONCEPTS EXPAND BEYOND PATHOGENS AND TOXINS

As the life sciences continue transforming (and being transformed by) research and development across a range of scientific disciplines, realizing the economic benefits of biotechnology research and development has become a critical part of scientific, economic, and national security efforts in the United States and globally.

Biotechnology-related research has great potential benefits, but compared to microbial hazards, little guidance is available to assist scientists with identifying, assessing, and mitigating the risks that arise with new advances and applications in biotechnology. Research involving multi-omics (the analysis of genomic, transcriptomic, proteomic, and metabolomic data), engineering biology (also known as synthetic biology), and artificial intelligence-enabled biological tools is often evaluated based on criteria relevant to infectious agents and toxins, shared Espona. However, these and many other biotechnologies are developed and used to address a much greater variety of issues, including environmental remediation, crop production, precision medicine, and energy. During the second workshop, Kavita Berger, National Academies, noted that existing frameworks governing research in the life sciences are focused primarily on genetically modified organisms, pathogens, or toxins. However, advances in biotechnology have expanded the possibilities of this research, with convergence between the life sciences and other disciplines, such as computer science and artificial intelligence, to design and create novel biotechnologies and living systems for nearly all critical sectors. “We quickly start to realize that if we want to focus on the benefits and reduce the risks, that our frameworks for addressing those are not necessarily reflecting the advances…in the research,” she said.

Research focused on the biotechnology-based economy is different from the pathogens and toxins that dominate the global health space, said Berger. Assessing risks and benefits may therefore require a different type of framework. She encouraged participants to consider which benefits and risks should be addressed, and how best to safeguard the benefits while reducing the risks.

Molecular biology is difficult and a double-edged sword, said Tessa Alexanian, IBBIS, in the final workshop, because of the difficulty in unlocking its potential for beneficial advances, such as drought-resistant crops, monoclonal therapies, or new vaccines. Unlocking the potential for harm is also difficult. Alexanian noted that biology offers the potential to do harm on a very large scale, but misuse is actually very rare because few people are motivated to do harm. Moreover, doing harm with biology is difficult (as is biology in general). Examples of harmful use have occurred, some carried out by state actors such as the Soviet Union, which developed anthrax for use as a biological weapon (Nikolakakis et al., 2023); by individuals, including the alleged perpetrator of the anthrax-laced letters sent to U.S. politicians and reporters in 2001 (FBI, n.d.); or by terrorist groups such as Aum Shinrikyo, which released sarin in a Tokyo subway in 1995 (OPCW, 2001). The 1995 attack involved chemical (not biological) weapons because the cult’s many attempts at developing a biological weapon failed, said Alexanian. Other terrorist groups “attempted to acquire biological weapons and just fell on their faces.”

Progression of Biotechnology Regulation

During the first meeting in the series, the committee discussed the progression of biotechnology regulation to provide awareness of policy development. The National Academies’ staff offered a brief history of the frameworks and policies that govern biological research. These frameworks aim to address the risks and/or benefits related to a range of biological research, with varying relevance to biotechnologies. The idea that beneficial research could be misapplied is not new, noted Berger, and policies on military use have been around for a long time. Policies aimed at preventing the use of biological weapons include the international Convention on the Prohibition of the Development, Production and Stockpiling of Bacteriological (Biological) and Toxin Weapons and on their Destruction (1972), which explicitly bans the development and production of biological weapons and distinguishes between military and peaceful, prophylactic intent. The Organisation for Economic Co-operation and Development (OECD) also established a Biological Resource Center (2001) to compile codes of conduct and other information from around the world, with the goal of identifying norms for peaceful, beneficial use of biological sciences research while protecting this research from harmful uses. Other policies aim to reduce the accidental release of biological products. In 1995, the OECD established a working group on Harmonisation of Regulatory Oversight of Biotechnology, which still exists and aims to reach global consensus on biosafety and other regulatory issues related to new biological products (e.g., vaccines, genetically modified organisms (GMOs)) (OECD, n.d.; 2006-2023).

New Attention on Biosecurity After 2001

Several new policies were instituted in response to the anthrax-laced letters that followed the World Trade Center attacks of September 11, 2001 in the United States. These policies included the United Nations Security Council Resolution 1540 (2004a, 2004b), which held nation states responsible for preventing and countering non-state actor threats involving biological (and chemical, radiological, and nuclear) agents within their countries. In 2004, the U.S. National Research Council (NRC, 2004) published Biotechnology Research in an Age of Terrorism, introducing the “dual use dilemma,” a concept that describes peaceful research that could be misapplied by a malicious actor to do harm. This report was prompted by concerns that terrorists could misuse peaceful, beneficial life sciences research to cause harm, following the revelation of the Soviet Union’s massive offensive biological weapons program in 1992 and the attempts of Aum Shinrikyo to obtain anthrax for use as a potential weapon. The report became a catalyst for U.S. and international efforts to address dual-use life sciences issues, said Berger. In December 2005, the InterAcademy Partnership (IAP), comprising 67 national academies of sciences

around the world, signed a statement on biosecurity (IAP, 2005) in advance of the 2006 Sixth Review Conference of the Biological Weapons Convention (BWC) (United Nations, 2005; 2006). The IAP continues to be involved in issues of international biosecurity, most recently a pilot project studying the risks and benefits of artificial intelligence and biology related to the BWC. The World Health Organization (WHO) produced guidance on addressing safety and security risks associated with life science research, focusing on the risk of pathogens and toxins to global health (WHO, 2010). This guidance was updated in 2022.

Potential Dual-Use Challenges Informed Current U.S. Policy

In 2011, the journals Science and Nature flagged two submitted manuscripts as containing information with dual-use potential, said Berger. The two papers had identified particular mutations in H5 protein that could increase transmissibility of H5N1 influenza viruses in mammals. This research was funded by the U.S. government to enhance pandemic preparedness, specifically to provide information that could help public health experts monitor and evaluate changes in natural influenza virus strains. The U.S. government commissioned a risk and benefit workshop in 2016 to discuss the potential biosafety and biosecurity risks and public health benefits associated with publishing this information (Institute of Medicine and National Research Council, 2015). The results of these efforts informed U.S. policy discourse regarding pathogens of enhanced pandemic potential, said Berger.

Research that combines engineering concepts and life sciences raises its own set of biosafety and biosecurity concerns, noted Berger. A National Academies consensus report, Biodefense in an Age of Synthetic Biology (2018), described a risk framework for assessing different types of research advances in synthetic biology (also referred to as “engineering biology”), including their vulnerability to exploitation or misuse by a malicious actor.

In 2019, the International Standards Organization (ISO) issued its first international standard for managing biological risks, both accidental and deliberate (ISO, 2019). This married the biosafety and biosecurity aspects of research involving pathogens and toxins, with a focus on high and maximum containment laboratories, said Berger. In 2022, the WHO updated the 2010 global guidance framework on life sciences research, defining a “middle space” that enables the benefits of the research to be reaped while also reducing the risks (WHO, 2022), she said.

FRAMEWORK AREAS TO CONSIDER

In the first workshop, participants were invited to discuss framework considerations and asked to assess the most significant risks to the bioeconomy and biotechnology. Berger outlined four specific issues the workshop might address. First, pathogens and toxins are important, but for these at least, frameworks, policies, and training programs exist. For emerging biotechnologies, on the other hand, frameworks for assessing risks and benefits and for guiding decisions about risk reduction approaches are limited, she said. She highlighted concerns about the digital life sciences ecosystem: data storage, sharing, software, and “how those systems can be exploited or affected in ways that don’t conform to how we think about biosecurity.”

A second consideration was protection of intellectual property and trade secrets, which are important for building and maintaining a robust bioeconomy. A third issue highlighted by Berger was the importance of the scientific community being proactive in addressing risks and benefits of new technology. “Every time a new technology emerges, if there is concern about whether it could be used for harmful purposes, or if it is actually misused, then the response gets very severe and significant,” she said. She gave the example of the emergence of synthetic biology in the 2000’s, which many found frightening at the time, prompting calls to restrict the research. Berger noted that all life sciences research contains risks and ethical concerns, but not addressing these in a proactive way risks “inviting regulation that may not allow us to advance in that area of research for public good.”

Lastly, the potential for biology and biotechnology to address societal problems that are unrelated to health and agriculture are promising but often not seen, said Berger. But given the availability of so many microbes that could potentially be helpful, e.g., by making cement- or textile-like materials, eating plastic, or capturing carbon, how can scientists leverage those traits and reap the benefits while reducing the risks? In addition to biosecurity and biosafety concerns, questions exist about how to assess the environmental risk posed by a designed microbe. Berger noted that the National Academies has embarked on a study reviewing approaches for assessing the environmental, biosafety, and biosecurity risks of one type of engineering biology, synthetic cell research and development.²

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² Study website: https://www.nationalacademies.org/our-work/external-review-of-environmental-and-biosafety-of-synthetic-cell-research-and-development (accessed October 28, 2025).

CHALLENGES OF IDENTIFYING RISKS IN EMERGING TECHNOLOGIES

Participants in the first meeting discussed the difficulties in identifying emerging biotechnology risks, and Espona noted that this is a perpetual challenge for the security and intelligence community. “The problem is that if biothreat reduction is working…nothing happens, and they cannot prove that it’s because of their work,” said Espona. She also noted that as technology evolves, risks and security also evolve, a situation that could get more difficult with the convergence of other technologies, such as artificial intelligence (AI). The system is dynamic and requires creativity and an alertness at all times to “what is new and what will be new in a few years.”

Scaling the Biological Weapons Convention (BWC) and Threat Reduction

Participants considered how the BWC might be applied to accommodate bioeconomy-related risks. Berger noted that the BWC has built-in cooperation and codes of conduct that exist for research that is relevant to the BWC (Johns Hopkins Center for Health Security, 2021; Johns Hopkins Center for Health Security, Tianjin University, The InterAcademy Partnership, 2021; Wang and Gronvall, 2021). In addition, training (IFBA, 2025) and certification (IFBA, n.d.) programs have been developed that support the norms of the BWC, but these programs primarily are focused on activities involving pathogens and toxins. The question becomes how to build on a foundation that was established to prevent the military development, production, and stockpiling of microbes for use as weapons, to support the peaceful development and beneficial use of other biotechnologies, said Berger.

After considering how the frameworks that have been developed mostly focus on preventing accidental and deliberate use of pathogens and toxins, the committee invited participants to examine existing frameworks and guidance for assessing and mitigating dual-use potential of biological research activities beyond infectious agents, including resources focused on responsible science and innovation (see Box 1-1).

Examining the Frameworks with an Emerging Technology View

Three biotechnologies were used to understand whether and how existing biosecurity governing frameworks can be used to assess and reduce risk and to consider potential information gaps for such assessments. The biotechnologies were: (a) human health multi-omics research and data management and access; (b) crop improvement multiomics research and data management and access; and (c) DNA synthesis screening and data management and access. Chapter 2 outlines the case studies.

Focusing on selected biotechnologies and research, the planning committee and expert participants discussed existing frameworks for assessing the risks of harmful exploitation of biotechnology data, knowledge, technologies, and equipment; and considered approaches to managing these risks while ensuring continued scientific progress and benefits from emerging biotechnology-related research and technologies. Chapter 3 summarizes the framework discussions. Common themes emerging from the case study discussions observed during the workshops are summarized in Chapter 4.