Introduction to Biosafety and Biosecurity for Potential Pandemic Pathogens and Dual-Use Research of Concern

All research that might result in a pandemic must undergo external review.

This study provides empirical data on the knowledge and practices of biosafety and biosecurity professionals and researchers involved in research on enhanced Potential Pandemic Pathogens (ePPPs) and Dual Use Research of Concern (DURC) within various U.S. sectors. The goal is to improve public health interventions and oversight for DURC and ePPP, contributing valuable insights for policy development. A notable finding was the association between larger biosafety/biosecurity teams and a higher likelihood of conducting high-risk biological research. A survey of 541 biosafety and biosecurity professionals was conducted between March 8 and 10 April 2024, with results analyzed using SAS at a significance level of 0.05. The study received approval from the Institutional Review Boards (IRBs) at Arizona State University and the University of Nevada, Reno. Government organizations were more likely to conduct DURC compared to other sectors (e.g., Academic, Commercial, Consulting). Public institutions reviewed more experiments outside the scope of the U.S. DURC Policy than private for-profit institutions. Institutions with larger biosafety/biosecurity teams reported greater research activity and more effective non-compliance reporting mechanisms (e.g., anonymous hotlines, reporting forms). Additionally, financial support and the challenges of policy implementation varied significantly across sectors. The findings emphasize the need for appropriate staffing and resource allocation for high-risk biosafety and biosecurity research. A differentiated regulatory approach and equitable distribution of resources are essential for effective oversight. Moreover, robust non-compliance reporting systems are critical to mitigating the risks associated with DURC and ePPP research.

Rapid acceleration in the science of genetic engineering of infectious diseases has outpaced legal and ethical frameworks for dealing with such research. Dual-use research of concern (DURC), which can be used for good or for harm, raises new questions about potential harm to human beings which have not traditionally been considered by medical research ethics committees, and may require us to revise and standardize ethical guidelines worldwide for the conduct of such research. The weighing of harm versus benefit of research as traditionally considered on an individual level needs to be considered on a population level for infectious diseases DURC, and on a global level due to the potential for transmissible infections to cause a pandemic, thus affecting people in places far from where the research was conducted. The harm of such research could result from either laboratory accidents or bioterrorism. As an example, engineered organisms such as influenza could result in an unnatural pandemic, affecting and harming people who were never informed of the research nor consented to it. The debate to date has been held among medical researchers and has been focused on the rights of researchers and scientific freedom. The community is also a stakeholder with rights, and DURC done in one country could cause harm to people in other countries who were never included in the debate. The first requirement is to inform and engage the public as a stakeholder in such research, and to make deliberations about DURC public and transparent. Secondly, governance structures and guidelines are not uniform internationally, and only some institutions and countries have specific DURC policies, none of which are enforceable. Consistent international guidelines and uniform, enforceable global governance models need to be developed for medical research ethics committees around potential population harm and benefit of DURC. Finally, researchers should be required to quantify potential population risks and benefits of DURC before it is approved. Models for quantifying risk–benefit equations could be drawn from health economics, with the onus on researchers to demonstrate that potential benefit outweighs potential harm. These would be positive steps towards protecting the interests and rights of all potentially affected populations in the case of transmissible infectious disease DURC. Past quantum changes in medical research governance such as mandatory registration of clinical trials show that major changes in research culture can be achieved. Current systems leave community stakeholders vulnerable to potential harms of infectious diseases DURC, and need to be addressed in a consistent and comprehensive manner internationally to ensure ethical obligations are met.

The Biological Weapons Convention (BWC) strictly prohibits State Parties from developing, producing, stockpiling or otherwise acquiring or retaining microbial and other biological agents that have no justification for peaceful purposes. At the time the convention was concluded, progress in the life sciences received little attention. Recent technological advances, especially in biotechnology, have brought attention, however, to the issue of dual-use research of concern (DURC). Dual-use research is defined as biological research with a legitimate scientific purpose that may, if misused, pose a biological threat to public health and/or national security. The most important and burdensome point of DURC is that we cannot escape the dual-use dilemma existing in all research activities. The DURC concept is an old but in a sense a new issue to be dealt with. Here we focus on the bioweapons and DURC – a subject that has received attention worldwide. In this review, we start with an overview of the historical development of bioweapons and then discuss their prohibition regimes focusing mainly on the BWC framework. Dramatic progress in biotechnology/recombinant DNA technology around the turn of the century brought a new experimental paradigm and affected the direction in which the life sciences should go. The Fink report and Lemon-Relman report have presented potential options for the healthy development of the life sciences. Exploring several important DURC case studies helps in understanding the nature of the dual-use dilemma more deeply. DURC in the area of the life sciences has been expanding broadly and has reached the neurosciences. Synthetic biology has introduced innovative approaches in creating novel living organisms. The convergence of chemistry and biology has become an inevitable stream in the recent development of the life sciences. Under these circumstances, the responsibility of scientists is becoming increasingly important. To deal appropriately with dual-use issues, risks and benefits must first be evaluated fairly and clearly, which makes the development of DURC evaluation methods an urgent issue. Both top-down approaches such as rules for smoothly processing of research, funding policies, and oversight mechanisms, and bottom-up approaches, i.e., researcher-oriented self-governance need to be mutually harmonized so that the life sciences may be applied more securely. The education of life scientists and the importance of outreach to society are also key means to success.

This study examines and compares dual-use research of concern (DURC) policies in the United States and Canada, two countries with advanced biosafety frameworks, to identify strengths, weaknesses, and areas for improvement in DURC governance. The study conducts a comprehensive review of current DURC policies, regulatory frameworks, and oversight mechanisms in the United States and Canada, analyzing key policy documents, including the 2024 U.S. Government Policy for Oversight of DURC and Canada's Human Pathogens and Toxins Act. Both U.S. and Canadian DURC policies require principal investigators (PIs) to conduct continuous project reviews throughout the research duration and maintain dedicated advisory agencies for biosecurity. Their approaches are notably multi-layered, integrating policymaking with educational initiatives and surveillance systems. However, important differences exist in their governance strategies. The United States has specific DURC policies primarily for federally funded research, while Canadian regulations apply to all facilities handling human pathogens and toxins. Notably, Canada also employs more detailed pathogen classification and quantity specifications than the United States and requires designated biological safety officers for oversight. While both countries maintain robust DURC oversight frameworks, they differ in their approach to governance, scope, and implementation. Based on this analysis, five key recommendations were developed. This includes establishing an international minimum standard for DURC regulation, extending U.S. DURC legislation to non-federally funded research, developing detailed risk-benefit analysis guidelines, and strengthening policies for responsible scientific communication.

According to the WHO, dual use research of concern (DURC) is "life sciences research that is intended for benefit, but which might easily be misapplied to do harm". Recent studies, particularly those on influenza viruses, have led to renewed attention on DURC, as there is an ongoing debate over whether the benefits of gain-of-function (GOF) experiments that result in an increase in the transmission and/or pathogenicity of potential pandemic pathogens (PPPs) are outweighed by concerns over biosecurity and biosafety. In this Viewpoint article, proponents and opponents of GOF experiments discuss the benefits and risks associated with these studies, as well as the implications of the current debate for the scientific community and the general public, and suggest how the current discussion should move forward.

Dual-use research poses a significant challenge for scientists in the biomedical field and for global health security in general. As the scientific knowledge and materials required for the development of biological agents become progressively more accessible and inexpensive, there is an increased need to understand and improve the governance of scientific research. Prevention of the misuse of facilities, equipment, agents, and scientific knowledge requires high levels of awareness of the concept of dual-use research, starting with early-career scientists and graduate students. In this study, the attitudes and level of awareness of postgraduate students in Pakistan toward the issues surrounding dual-use research were assessed through a survey containing both quantitative and qualitative questions in 32 universities in 4 provinces, federal area, and Azad Jammu and Kashmir regions of Pakistan; 933 students responded. Most (58.2%) had never heard of dual-use research of concern (DURC), while 18.5% had heard the term but were unsure of its meaning. Irrespective of prior knowledge, a higher percentage of students (68.6%) felt an obligation to report research misuse. Considering the need for DURC training, 94.1% of the respondents agreed that the principal investigator should take the responsibility to train students on DURC at the start of a research project. When experimental results having dual-use potential, 69.1% indicated they would publish with limited protocol, with 43.5% indicating they would publish the limited protocol only if there was a way for scientists to access their data. The survey results revealed limited DURC awareness among researchers across Pakistan. However, the respondents, although not formally educated about DURC, were quite aware of its impact. The information gained in this survey will be valuable in addressing country-specific awareness and training needs.

Governance of high-risk biological research, specifically dual-use research of concern (DURC) and pathogens with enhanced pandemic potential (PEPP), is a topic of renewed interest. This study considers the historical evolution of biosecurity policies, highlighting current challenges in balancing scientific progress with national security and public safety. A historical analysis and a literature review were conducted, examining significant events and policy developments shaping biosafety and biosecurity in the United States. The study also reviews possible frameworks for governing DURC and PEPP, assessing ethical, political, and regulatory perspectives from relevant literature. Findings indicate that biosafety and biosecurity policies have historically been reactionary, responding to specific incidents rather than proactively managing risks. Despite significant policy efforts, gaps in transparency, oversight, and international collaboration persist, raising concerns about the effectiveness of governance structures. However, looking at past frameworks for managing high-risk biotechnological risks may be beneficial in establishing future governance strategies. The study suggests the need for a balanced approach that integrates ethical, social, legal, and other considerations to ensure robust oversight of DURC and PEPP. Continuous policy evolution, informed by empirical evidence and interdisciplinary collaboration, is needed for mitigating risks associated with high-stakes biological research. Effective governance of DURC and PEPP requires comprehensive, interdisciplinary approaches that incorporate historical lessons, ethical considerations, and adaptive policymaking. Collaboration between policymakers, scientists, biosafety and biosecurity professionals, as well as members of the public, is required to ensure scientific innovation benefits national security and public health while minimizing risks.

After a decade of intensive policy discussions on the topic of dual-use research of concern (DURC) in the life sciences, there has been a lack of consensus on how to practically define DURC; whether it is feasible to identify and regulate DURC experiments; how to address the risks associated with DURC; and how to balance this risk with the necessity of fostering life sciences research for public health and biodefense. The publication of two avian influenza studies has brought the DURC issue back into sharp focus and has resulted in a new set of federal guidelines. However, the new DURC policy raises questions regarding whether this is the best policy solution to a complicated biosecurity concern.

Capacity building for the identification, mitigation, and communication of DURC in Pakistan: A cross-sectional study

One of the main prerequisites for creation and dissemination of bioethics in the world was the concept of dual use in medical and biological sciences, which is defined as the direction of unintentional creation of biological threats in research or implementation of new biotechnologies. To determine the range of dual-use research that could potentially generate products, technologies, or knowledge whose misuse could harm large numbers of people or the environment and that are biosafety-relevant, the international term Dual Use Research of Concern (DURC) is used. Actualization of the debate on the dilemma of dual use in biomedical sciences is due to, on the one hand, the international community's attempt to minimize the potential for destructive use of biomedical research, on the other hand, the active search for effective ways to raise awareness of their social and moral responsibility for implementation of the results of scientific developments in the field of life. This article considers the definition of terms that define the field of DURC in the context of biosafety, which in recent decades have undergone a number of semantic changes. The article also outlines the modern general concept of DURC, defines the categories by which DURC is defined, and outlines the scope of policy on the implementation of control over DURC. Informing the scientific community engaged in biomedical research about the problem issues of DURC biotechnology is a key component of biosafety. Modern biotechnology and related biosafety issues should be applied to society needs, but without compromising human and environmental safety. Systematic consideration of all these disputable questions of the dual-use dilemma with the involvement of all stakeholders will allow to form a rational biosafety policy for biotechnology.

Fervent attention was paid to what is coined dual-use research (DUR), or research that can both benefit and harm humanity, and dual-use research of concern (DURC), a particular subset of...

Regulating dual-use research: Lessons from Israel and the United States

The potential use of biological knowledge for nefarious purposes has attracted significant concern. The field of microbiology has come under particular scrutiny because some microbes and toxins are potential agents for bioterrorism and biological warfare. In 2005, the U.S. government established the National Science Advisory Board for Biosecurity (NSABB) to address issues related to biosecurity and dual-use research (http://osp.od.nih.gov/office-biotechnology-activities/biosecurity/nsabb). Over the past decade, the NSABB has considered several topics, including defining the boundary between research that requires no special oversight and research that could be misapplied, which is known as dual-use research of concern (DURC). One of the major accomplishments of the NSABB was to draft a definition for DURC as “life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be directly misapplied to pose a significant threat with broad potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security.” In addition to defining the type of research that should elicit heightened concern, the NSABB recommended that research be examined for DURC potential throughout its life span, from experimental conception to final dissemination of the results (http://osp.od.nih.gov/sites/default/files/resources/Framework%20for%20transmittal%20duplex%209-10-07.pdf) and developed tools for communicating findings that meet the definition (http://osp.od.nih.gov/sites/default/files/resources/Communication\_Tools%20\_Dual\_Use\_Potential.pdf). Furthermore, the NSABB sought to establish a culture of responsibility to mitigate risks associated with DURC that extended through the entire scientific enterprise and included journals and editors. In 2007, the American Society for Microbiology (ASM) responded to the NSABB directives by introducing a questionnaire in the manuscript referee review form used by its journals that asked reviewers to provide an assessment about whether the work involved experiments of concern. Since the winter of 2012, the discipline of microbiology, and the field of virology in particular, has been convulsed by controversy …

Gain-of-function research.