Charting a New Course for Biosafety in a Changing World

By David Gillum, Rebecca Moritz, Yong-Bee Lim, Kathleen Vogel

Over the last decade, even prior to the COVID-19 pandemic, concerns about biological safety have been growing. Biosafety’s goal is to reduce the risks associated with handling infectious agents, toxins, and other biological hazards. But recent events—such as the discovery of smallpox vials outside of high containment labs, the transport of inactivated anthrax around the world, and safety concerns around gene drives and a future with do-it-yourself genome editing—highlight gaps in how biosafety governance currently operates.

These emerging issues, coupled with uncertainties about the origins of SARS-CoV-2, have led to a flurry of recent discussions around modernizing oversight mechanisms for biosafety. At the international level, the World Health Organization (WHO) is proposing the development of a framework to mitigate biological risks. And in the United States, Senator Patty Murray introduced the PREVENT Pandemics Act in March 2022, which aims to help prepare for and prevent future pandemics by expanding oversight of key research areas and providing funding to build the knowledge base for safely conducting research activities.

There is now an opportunity to reconsider the governance of biosafety and chart a new course for its future. However, current proposals largely mirror historical precedents and are reactive, overly broad, and inconsistent. If implemented, a system with these characteristics could be detrimental to public health and life sciences research, as well as the emerging bioeconomy. By contrast, a well-designed biosafety strategy could enhance safety while catalyzing scientific innovation, economic growth, and public benefits. Current efforts should break with tradition and take a fresh, proactive, risk-based approach to understand, detect, and mitigate biosafety risks. 

Origins of modern biosafety

Over the past 70 years, the principles and practices of biosafety have mostly remained unchanged, and their uncoordinated application has led to an uneven patchwork of biosafety governance mechanisms. As a result, oversight fluctuates according to the country where the work is taking place and whether it is funded by government or industry. Further variance is introduced based on whether the work involves human or animal pathogens, naturally occurring or genetically modified organisms, or uncharacterized agents. This dynamic—where biosafety is defined, understood, and implemented differently under disparate systems around the world—is in itself a challenge.

A well-designed biosafety strategy could enhance safety while catalyzing scientific innovation, economic growth, and public benefits.

Today’s inconsistent systems are a direct result of the history and evolution of biosafety. In the United States, bioweapons research facilities such as Camp Detrick, later renamed Fort Detrick, established rules to mitigate the risks of dangerous pathogen research and development activities. These included procedures to protect laboratory personnel and the surrounding community when handling high-risk pathogens and conducting trials that exposed animals to infectious aerosols and biological toxins to understand the effects of such substances.

The first important advance in biosafety occurred in April 1955, when personnel from Fort Detrick and other US Army biological warfare laboratories gathered for the first time to discuss infection control, decontamination methods, and physical containment. This became an annual event that continues today, with experts sharing biosafety-specific information across military research and, later, all life sciences. Building a community of safety professionals that gathers on a regular basis has been one of the more successful strategies in enhancing biosafety oversight, providing a way to share challenges and best practices and helping to grow biosafety expertise across the network.

The advance in governance came at the Asilomar conference in 1975, where scientists gathered to better understand the risks of novel biological experiments and the recombinant DNA revolution in the early 1970s. This led to one of the earliest government policies to address biosafety risks—the 1976 National Institutes of Health (NIH) recombinant DNA guidelines—but the guidelines largely left the community to police itself. The main enforcement mechanism was the revocation of federal funding, leaving the guidelines entirely optional at institutions with private funding. Today’s patchwork of governance modes, where work with DNA remains self-regulated but other research—with pathogens, for example—may be more heavily regulated, got its start at this time.

Building a community of safety professionals that gathers on a regular basis has been one of the more successful strategies in enhancing biosafety oversight.

The 1980s saw the development of best practice guidance documents. This guidance remains the fundamental underpinnings for how biosafety is conducted to this day, but it requires constant updating. WHO published the Laboratory Biosafety Manual, and the Centers for Disease Control and Prevention (CDC) and NIH published Biosafety in Microbiological and Biomedical Laboratories. These documents use risk assessment methodologies to inform appropriate biosafety measures, marking a big step forward for the biosafety community.

In the mid-1990s, fear of weaponized biological agents motivated a new set of changes in governance. In 1995, the Japanese cult Aum Shinrikyo released sarin gas on three subway trains in Tokyo, killing more than a dozen people and injuring thousands. The group also attempted to develop biological weapons and other capabilities to prove an apocalyptic prophecy. And in the United States, Larry Wayne Harris, a microbiologist linked to white supremacist groups, ordered three vials of the bacterium that causes bubonic plague from a global biological repository. In response to cases like this, Congress passed the Antiterrorism and Effective Death Penalty Act of 1996, which prohibited individuals from acquiring biological agents or toxins that could be used as a weapon. Further restrictions were placed on certain biological agents and toxins in the early 2000s with the Federal Select Agent Program, which established processes to govern the possession and use of specific agents and toxins that can be used for bioterrorism. And in the 2010s, several additional oversight policies intended to limit possible misuses of certain pathogens were implemented.

As this history demonstrates, biosafety policies have generally been enacted in a reactive, rigid manner, focusing on lists of agents and subsets of experiments or specific experimental outcomes. Furthermore, a patchy implementation means that privately funded, international, and DIYbio experiments are all likely to fall outside the realm of existing governance, which is geared toward government-sponsored research. This approach is inadequate in today’s life science research enterprise, where such clear boundaries cannot be drawn and the risks are much broader.

A patchy implementation means that privately funded, international, and DIYbio experiments are all likely to fall outside the realm of existing governance, which is geared toward government-sponsored research.

The field of biosafety perennially wrestles with the question of how much risk is acceptable. Underlying this debate is a push-pull dynamic between increasing regulation and stifling science. As legal scholars Gary Marchant and Lynda Pope note in “The Problems with Forbidding Science,” attempting to regulate new developments in the life sciences adds layers of complexity to the process of executing and providing oversight on projects. It also complicates the sharing and validation of study data and findings. When they are not closely tied to site-specific hazards and risks, such requirements may become time-consuming exercises in compliance that detract from research activities without actually mitigating risk or increasing safety.

The new biosafety regulations proposed by Congress and WHO have yet to strike the right balance between caution and innovation. The challenge is how future biosafety governance should be structured to understand and mitigate risk. Misdirected or reactionary governance becomes unhelpful. A system that is adaptable and scalable, by contrast, will be more successful at protecting society while fostering innovation.

Building a better path forward

It is time to consider how biosafety might evolve to be more proactive, to be tiered to risk while being universally applicable (regardless of funding, institution, or borders), and to be nimble enough to keep up with scientific innovations. As biotechnology advances, new strategies and tools are needed to help assess, inform, and manage biological risks. Here, we emphasize four main areas for improvement: research, reporting, knowledge and training, and risk-based approaches.

As biotechnology advances in laboratories as well as in agriculture and industry, there is a critical need for research to help better assess true biological risks and hazard mitigation measures for the purpose of informing more effective biosafety policies. One of the greatest strengths of the PREVENT Pandemics Act is that it places an emphasis on funding basic biosafety research. However, the bill should go further by creating centers for biosafety excellence that are designed to anticipate and prevent future biological risks while increasing collaboration with policymakers and other stakeholders. If such centers were created around the globe, they could ultimately unite to form a biosafety structure, perhaps one similar to that of the International Atomic Energy Agency.

The field also needs a standardized, international system for reporting accidents and other biosafety incidents. Such a system will help to better understand global risks, reduce future incidents, and increase public trust. Building one that balances all the factors—transparency and intellectual property concerns, defense and biosecurity, and information about potential dual uses of pathogens—is extremely difficult. But as biotechnology continues to develop, potentially risky research will spread to a wider range of institutions and spaces—especially those that may not have much institutional biosafety support, such as DIY laboratories or low-resourced institutions and countries. Thus this reporting system must be designed for a broad array of settings. The PREVENT Pandemics Act should create and enforce the implementation of a nonpunitive, anonymous incident reporting system, such as those used in aviation, healthcare, and nuclear power. It should also allocate permanent funding for biosafety positions in public health laboratories.

As biotechnology advances, new strategies and tools are needed to help assess, inform, and manage biological risks.

One of the most effective tools for reducing research risks is to create awareness about the importance of biosafety and train the next generation of responsible scholars and practitioners. Although the PREVENT Pandemics Act focuses on enhancing biosafety training for those working with or near federal select agents or toxins, biosafety principles and practices should be incorporated into the science, technology, engineering, and medicine—STEM—fields starting with elementary school and continuing through undergraduate and graduate education, as well as in community labs. This training can be in-person or through online modules or courses. The public must have easy ways to access biosafety expertise, such as the Ask a Biosafety Expert website. Originally created by and for the DIYbio community, funding for programs like this should be expanded. And because these education and awareness efforts reach different audiences in unique ways, they should be rigorously evaluated for impact and long-term efficacy.

More generally, the biosafety field needs to broaden its approach to public outreach. At a minimum, biosafety knowledge needs to be free, accessible, and distributed in a fair and equitable manner. There should be universally available templates for biosafety training, procedures, and manuals to help guide others. The International Organization for Standardization’s ISO 35001, which sets a standard for biorisk management systems, costs over $100—a prohibitively expensive price for scientists in developing countries or people working in community labs or public school settings. Likewise, development of future biosafety frameworks and consensus standards should include consultation with a broad set of stakeholders, including biosafety and other relevant scientific practitioners, social scientists, government officials, and members of the public. Not only will such groups be key to establishing a minimum standard for biosafety practices and policies for the global community, but they will also be essential to the standard’s dissemination. 

One of the most effective tools for reducing research risks is to create awareness about the importance of biosafety and train the next generation of responsible scholars and practitioners.

To be effective, future biosafety frameworks need to move toward a risk-based situational analysis rather than relying on lists and other instruments that quickly become outdated. These standards should be based on the risks of the activity being performed while accounting for site-specific hazards. Unlike today’s varied biosafety rules, a new framework should provide guidance to help bring all laboratories working with biological materials up to a minimal level of safety commensurate with the specific risk assessment for the institution, region, and country. A compendium of biosafety resources, including templates for biosafety training, procedures, response plans, and other best practices, would help create a culture of continuous evaluation and learning. This approach should incorporate processes for evaluating incidents and sharing them in a nonpunitive way so others can learn from what happened and determine how to prevent future problems.

Finally, it is worth emphasizing that the concept of biosafety evolved separately from biosecurity, and the two constitute different fields and mindsets. Biosafety has historically been geared toward protecting laboratory personnel and preventing laboratory-acquired infections and accidental releases that may impact the community or the environment. Biosecurity, by contrast, involves preventing the intentional misuse of the life sciences. Mingling them risks reducing both safety and security while potentially making the governance patchwork more, rather than less, complex. Unfortunately, WHO’s aforementioned draft framework to mitigate biological risks and dual-use research appears to do just that. The document attempts to establish structures and procedures for “biorisk management,” which WHO defines as including biosafety, biosecurity, and dual-use research. Practically speaking, this is problematic because biosafety has roots in microbiology, public health, and worker safety, while biosecurity has more in common with national defense and law enforcement, involving secrecy and gates, guns, and guards. It is rare for biosafety practitioners to be deeply knowledgeable in biosecurity, and vice versa.

A new framework should provide guidance to help bring all laboratories working with biological materials up to a minimal level of safety commensurate with the specific risk assessment for the institution, region, and country.

Thus the complex interactions and unintended effects of combining biosafety and biosecurity must be navigated carefully at a policy level, tested at the practitioner level, and revised through deliberations with diverse groups of stakeholders. Although the biosecurity community has had more experience considering how experiments or agents could be misused, biosafety practitioners may need to adapt their traditional focus and mindset into one that also considers security. This transformation in biosafety thinking has been likened to encouraging people to imagine potential harms from research that is well-intentioned, perhaps akin to the way organizations use “white hat hackers” to protect computer networks. On the biosecurity side, the change in thinking takes the form of balancing the risks of information hazards with the need for transparency and minimizing barriers to innovation so the life sciences can fulfill its promise for positive ends.

At this critical juncture for the field of biosafety, the PREVENT Pandemics Act and the WHO framework present opportunities to rethink conceptions of biosafety so they align with current and future needs. To do so, these systems must shed the reactive characteristics of the past and instead be proactive, risk-based, universally applicable, and nimble. They must encourage scientific advancement while balancing the ever-growing and increasingly difficult need to predict risks inherent in the modern bioeconomy. Given the expanse and growth of the life sciences across the entirety of society, making this new model open and accessible is critical. Everyone involved in the life sciences—including the public—should have access to workable and adaptable biosafety resources. By better preparing all practitioners and stakeholders to assess and engineer risk out of future biological experiments, they can grow the bioeconomy while making the world safer in the process.