A Framework for Tomorrow’s Pathogen Research

Final Report


Ravindra Gupta

Ameenah Gurib-Fakim

Shahid Jameel

David Relman


Jesse Bloom

Filippa Lentzos

February 2024


Safe, secure, and responsible high-risk research

Joseph Rotblat, a physicist who quit the Manhattan Project and later helped establish the Pugwash Conferences on Science and World Affairs, with which he shared the 1995 Nobel Peace Prize, wrote “Scientists can no longer claim that their work has nothing to do with the welfare of the individual or with state policies” (Rotblat 1999). To ignore the societal implications of their work is “immoral,” he reasoned, because “… [an immoral attitude] eschews personal responsibility for the likely consequences of one’s actions.”

Today, it is widely recognized that scientists—especially those doing high-risk research—have a professional obligation to both consider the broader ends of their science and mitigate anticipated harmful consequences (WHO 2022).

Consequently, responsible stewardship of science today is expected to include a prominent role for scientists in developing and supporting policies (including laws, regulations, standards, guidelines, best practices, codes of ethics, research review processes, and training and education) that reflect the local, national, regional, and global communities’ values, priorities, and risk-taking strategies. This stewardship entails developing and supporting ethical practices (with particular attention to issues of intent, integrity, and conflicts of interest) to ensure an effective alignment of the processes and outcomes of science with societal values, needs, and expectations. To ensure their sustainability, these practices require a commitment to public education, engagement, and empowerment.

Taskforce on Research with Pandemic Risks

The continuing coronavirus disease 2019 (COVID-19) pandemic has highlighted the potential devastating impact of a single virus. In the coming years, the human population’s encounters with high-consequence pathogens may occur more frequently (Carlson 2022; Gilbert 2022). Human-driven alterations of the natural environment and climate-driven changes in ecosystems may provide increasing opportunities for viruses to cross species barriers, including to humans. In addition, field collection and experimental manipulation of potential pandemic viruses under some circumstances can increase the risk of accidentally, inadvertently, or intentionally seeding a pandemic.

The Bulletin of the Atomic Scientists recognized that a multi-disciplinary, international forum was needed to consider trends and oversight of high-risk research on pathogens with a narrow focus on the potential benefits and harms of research with known or potential pandemic pathogens. In 2022, the Bulletin convened an independent panel of experts: the Task Force on Research with Pandemic Risks. Its aim was to foster an inclusive and broad discussion and to identify ways and means for research with pandemic risk to be managed as safely, securely, and responsibly as possible.

The remit of the Task Force was to focus on the risks and benefits of a subset of research that could plausibly source a large outbreak, or even a pandemic, due to accidental or inadvertent actions during the conduct of experiments, or that results in information that could be misused by a malicious actor. The accidental and inadvertent risks generally concern biosafety whereas the malicious actor risk generally concerns biosecurity, though these boundaries are approximate (Evans, Lipsitch, and Levinson 2015). The Task Force’s scope included (1) research on pathogens known to be capable of causing a pandemic that under current conditions (e.g., low population immunity) could result in extensive spread beyond the current infection burden, (2) manipulation of pathogens that are not currently thought capable of pandemic spread in ways that can be anticipated to increase their capacity to cause a pandemic (e.g., by increasing virulence or transmissibility), and (3) research on pathogens with unknown characteristics. The Task Force was to critically review the handling of such pathogens throughout the research lifecycle, from collection in the field and transportation to sites for research, to characterization, cultivation, and manipulation in the laboratory, to disposal at the end of research.  Taking its lead from the US National Science Advisory Board on Biosecurity (NSABB), the Task Force understood enhanced potential pandemic pathogen research to include (NSABB 2023):

“… research that is reasonably anticipated to enhance the transmissibility and/or virulence of any pathogen … such that the resulting pathogen is reasonably anticipated to exhibit the following characteristics that meet the definition of a PPP [potential pandemic pathogen]:

  • Likely moderately or highly transmissible and likely capable of wide and uncontrollable spread in human populations; and/or
  • Likely moderately or highly virulent and likely to cause significant morbidity and/or mortality in humans, and
  • Likely to pose a severe threat to public health, the capacity of public health systems to function, or national security” (italics added for emphasis).

Like the NSABB, the Task Force took reasonably anticipated to mean a non-trivial probability assessment by individuals with relevant scientific expertise. It does not require high confidence that the outcome will definitely occur. This wording, however, does exclude research for which experts would anticipate the outcome to be technically possible but highly unlikely. In the case of newly discovered pathogens that are not yet well characterized, it is often particularly challenging to assess how individual experiments (such as serial passaging in human cells or introducing features or genes from similar pathogens) might alter transmissibility or virulence. Thus, when these biological properties cannot be anticipated for newly discovered pathogens, it should be assumed that the pathogen is a potential pandemic pathogen (and therefore managed at the corresponding biosafety level) when its taxonomically close relatives include pathogens with those characteristics.

Virologists conduct research with potential pandemic pathogens mainly to increase knowledge about these pathogens, improve surveillance, and to inform the design of diagnostics, vaccines, and therapeutics. However, the risks associated with enhanced potential pandemic pathogen research can be exceptionally high, and probabilities of harm increase with the number of such studies undertaken (Klotz and Sylvester 2012).

There has been considerable progress in the ability of virologists to rapidly detect and sequence the genomes of viruses, including those that could potentially harm humans, other animals, plants, or the environment (although the ability to predict function from sequence alone remains limited). At the same time, the ability to generate fully replication-competent viruses, or to re-construct extinct pathogens based solely on their genetic sequence has improved. Large poxviruses, which have long genomes, (Noyce, Lederman and Evans 2018) and viruses with short genomes (e.g., influenza A virus, polioviruses, and betacoronaviruses can be created using synthetic DNA (Tran et al. 2020; Xie et al. 2020). Generating some of these viruses from synthetic DNA is undertaken by many, reasonably resourced virology laboratories, and the accessibility and efficiency of these techniques is likely to continue to increase.

The intersection of these advances has increased the capacity of scientists to identify the genome sequences of potentially high-risk viruses, and then generate the actual pathogen in the laboratory from knowledge of the sequences, including modified versions. This capacity has yielded benefits. For instance, it has enabled the engineering of attenuated viruses for vaccines (Trimpert 2021) and helped in the development of countermeasures that are harder for viruses to escape by acquiring resistance (Starr 2021). Further, some experiments are safer because of using attenuated viruses in place of wild-type viruses. Experiments with attenuated viruses can be performed at lower biosafety levels, which accelerates research progress. Moreover, these capabilities can reduce the need for collection of replicative (“live”) virus samples from the field, since one of the main reasons to acquire live samples from nature is to obtain virus isolates for countermeasure development. These viruses can now also be generated using reverse “on-demand” genetic systems, which enable rescue of wild-type viruses from synthesized nucleic acids in high or maximum containment based only on sequences that were determined using inactivated natural samples, i.e., samples that do not contain “live” viruses anymore and that do not necessarily have to be transported across country borders (Beitzel 2021). However, this increased capacity has also increased the ability of scientists to create and work with viruses that could accidentally or intentionally cause harm, in some cases with potentially devastating global consequences.

Because research with potential pandemic pathogens will never be risk-free, navigating in this high-risk research space warrants additional precautions, including traffic signals (e.g., red lights identifying research that should not be undertaken and yellow lights identifying research that requires caution and close oversight), guardrails (e.g., introducing enhanced biorisk management), speed bumps (e.g., ensuring additional multi-disciplinary review of some research or imposing temporary moratoriums), and lamp posts (e.g., illuminating safer directions for research and including proportional oversight to protect the well-being of humans, other animals, plants, and the environment).

The overarching aim is to create a safe, secure, and responsible research environment for researchers, and in so doing, to earn public trust.

Work of the taskforce

The Bulletin established a year-long Task Force on Research with Pandemic Risks comprising 28 international experts across fields such as anthropology, bacteriology, bioengineering, biorisk management, biotechnology, epidemiology, ethics, global governance and policy, infectious disease, law, political science, security studies, sociology, synthetic biology, as well as virology. Task Force members joined in their individual capacities and not on behalf of the institutions at or for which they work. A list of Task Force co-chairs, directors, members, rapporteurs, and Bulletin staff involved in the project is found in Appendix I.

The Task Force convened online six times from October 2022 to October 2023. In addition, the Bulletin and the Task Force met in Geneva, Switzerland, on April 19-21, 2023. The meeting in Geneva also included policy leaders, journalists, scientists, and nongovernmental organization leaders. To further enhance engagement, deliberations were live-streamed and recorded (Bulletin 2023).

This report is the result of the Task Force’s deliberations. The Task Force is independent of the Bulletin and is solely responsible for the content of the report. Its members were asked to join a consensus signifying that they endorse “the general policy thrust and judgements reached by the group, though not necessarily every finding and recommendation.” Each Task Force member had the option of putting forward an additional or a dissenting view, although the goal was always consensus-building.

Structure of the report

The report includes several sections. Section II introduces virology research and its key potential benefits and outlines how advances in science and technology potentially increase certain benefits. Section III focuses on some of the risks of virology research, including biosafety and biosecurity, and outlines how advances in science and technology potentially increase some of these risks. Section IV focuses on ethical obligations to make research with pandemic risks more safe, secure, and responsible. It also suggests actionable and sustainable strategies to effectively maximize the potential benefits and mitigate the foreseeable potential harms of research with known or potential pandemic pathogens, while attending to issues of equity and proportionality. Section V argues for empirical studies on biosafety and biosecurity to make research with pandemic risks more safe, secure, and responsible. Section VI reviews the contemporary governance space for research with known or potential pandemic pathogens and argues that effective legislation, regulations, policies, and guidelines specifically regulating such research will strengthen the scientific enterprise and should be put in place without delay. Section VII discusses challenges in building and sustaining trust in science in general and research with pandemic risks more specifically. The Task Force’s recommendations follow in Section VIII of the report.


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[1] Discussion around risks in virology and microbiology have sometimes included the term “gain of function,” which was the phrase applied to controversial research that modified H5N1 influenza A virus to transmit among domestic ferrets in the laboratory (LINK). However, this term when used generically lacks specificity in capturing risks, since formally speaking “gain of function” can just mean introducing any new trait into an entity (a virus in this case). For instance, modifying a non-transmissible oncolytic virus used for cancer treatment to improve infection of cancer cells would technically involve a gain of function by this virus, but in practice such research would likely be beneficial for public health with little risk.