By Lillian Parr

In the coming months, the public is likely to hear more about dual-use research of concern (DURC), a category of risky research whose governance is currently under review by the National Science Advisory Board for Biosecurity (NSABB). This post highlights important recommendations made by a group of policy experts, researchers, and scientists to frame what outcomes we hope to see from the NSABB Review.

Background

Over the past year, COVID-19 vaccines have saved millions of lives, demonstrating the immense value of life sciences research for combatting biological threats. Some biological research, however, may create more risks than potential benefits. Often referred to as dual-use research of concern (DURC), this type of research is generally conducted with positive intentions but could potentially have harmful effects if misused. 

Such research often involves engineering pathogens to be more virulent or transmissible through a process commonly known as gain-of-function research. Scientists who conduct this work view it as necessary to understand biological features of the pathogen in question and note that the data generated is often useful in epidemiological surveillance. Through conducting this research, these scientists believe that they will gain the knowledge needed to develop effective countermeasures or other response technologies. A prominent example of this type of work can be seen in a controversial 2012 study published in Science, in which researchers used a combination of genetic engineering and serial infection of ferrets to direct the evolution of the avian H5N1 flu into a variant capable of airborne transmission in mammals. 

Another form of DURC is the de novo synthesis, or the synthetic re-creation, of dangerous viruses. In 2018, a research team in Canada successfully constructed a functional horsepox virus using synthetic DNA and published the full protocol in an academic journal. Though horsepox is not harmful to humans, there were concerns that the detailed instructions in the paper could be used to create smallpox, a disease that is genetically similar to horsepox and which has grave effects on human health. 

Technical capabilities and access to knowledge in the life sciences have increased substantially over the past decade, creating ever-expanding opportunities. The ability to precisely and easily engineer organisms has enabled more productive crops, bacteria that express medically relevant proteins, cancer therapies, and a host of other useful tools. However, advances in the life sciences have also brought new risks to research—DURC can now be conducted more efficiently and easily, and more researchers than ever before will potentially have the skill sets and resources to carry out this type of work. 

There are several risks here. First, the publication of sensitive information significantly lowers the barrier to bad actors who wish to either engineer pathogens or create them de novo. While openly sharing information via publications is core to the ethos of research and enables scientific progress, some publications create risks that outweigh these considerations. 

Additionally, even if gain-of-function research is conducted by a laboratory that does not intend harm, there is a possibility of samples being stolen by rogue actors who may then go on to use them for malicious purposes.

There is also a risk of an accidental infection of a lab worker, who could then go on to infect community members—lab accidents are uncommon but not impossible, and the leak of an engineered pathogen could have grave outcomes. Accidents may also occur in the transport of pathogens. For instance, in 2014 the CDC inadvertently sent samples of the highly pathogenic H5N1 influenza virus to a USDA lab in lieu of a relatively harmless animal influenza strain. Similarly, in 2015 an Army laboratory mistakenly distributed live anthrax samples to several facilities, resulting in up to 22 exposures at a U.S Air Force base in South Korea. 

U.S. DURC Regulations & Policy Review

To address these risks, there are several policies in place to govern DURC in the United States. U.S. Health and Human Services (HHS) uses a framework to regulate the research of enhanced pandemic potential pathogens (ePPPs)—meaning pathogens that have been engineered and are deemed capable of setting off a pandemic. The Framework for Guiding Funding Decisions about Proposed Research Involving Enhanced Potential Pandemic Pathogens (HHS P3CO Framework) allows for some ePPP research to be funded as long as it complies with strict biosafety regulations, and as long as there is no safer way to get the results researchers seek. This framework is complemented by and in accordance with policy guidance from the White House Office of Science and Technology (OSTP), titled Policy Recommended Policy Guidance for Departmental Development of Review Mechanisms for Potential Pandemic Pathogen Care and Oversight. 

The HHS P3CO Framework indicates that decisions on funding gain-of-function will be guided by a panel of experts, known as the HHS P3CO Review Group. However, the group is limited to an advisory capacity, and is rarely consulted—since the system was put in place in 2017, only three projects have been referred for review. Experts have also raised concerns about the lack of transparency, as the names of members of this panel, as well as their deliberations, are not available to the public. Furthermore, the processes outlined in the framework are somewhat vague and viewed as too narrow and weak by some biosecurity advocates.

More broadly, the U.S. Government’s Policy for Oversight of Life Sciences DURC provides a framework for which DURC projects should be allowed federal funding. This document outlines fifteen pathogens and seven experiment types that require special attention for federal funding agencies, and outlines how this research should be funded and regulated. Like the HHS P3CO Framework, some experts regard this document as lacking clarity and having an inappropriately small scope. 

To address these concerns, in January 2020, the National Science Advisory Board for Biosecurity (NSABB)—a federal advisory committee that sits under the NIH—was tasked with evaluating U.S. DURC policies, as well as providing recommendations for how to balance security and transparency with regard to the publication of research findings. While this process was put on hold to allow NSABB members to focus their full attention on the COVID-19 response, HHS convened a meeting of the NSABB to restart this effort in February 2022. At that meeting, NSABB members met with HHS and OSTP officials to discuss logistics and goals for the review process. 

The review is slated to be ongoing until October 2022, at which point the NSABB will deliver their recommendations. 

Expert Recommendations

This process is a key window of opportunity for biosecurity stakeholders to ensure that U.S. Government policies effectively frame and regulate DURC policy. To this end, a group of scientists and policy experts, including Christine Parthemore and Andy Weber of the Council on Strategic Risks, recently released a statement with recommendations for the NSABB to consider. This statement includes considerations for covering HHS and OSTP’s P3CO guidance (jointly referred to as the ePPP Framework) as well as the U.S. Policy for Oversight of Life Sciences DURC. 

The statement provides some common sense measures to strengthen and clarify the policies, which are summarized below: 

• Expand the scope of pathogens governed by the ePPP Framework: In addition to broadening the criteria for ePPPs, the experts also recommend giving stronger consideration to the risk of information hazards, arguing that there is insufficient oversight of sequence information of ePPPs.

• Assess and Detail Risks and Benefits: The statement recommends a clearer and more robust risk/benefit analysis for proposed ePPP research, including explicit categories of risks that should be taken into consideration. Additionally, it suggests that research should be judged by its practical and actualizable benefits, rather than hypothetical claims of what the research could do that may be unrealistic given existing infrastructure. 
• Clarify Processes that are Nebulous or Insufficient: There are several aspects of the ePPP framework that the statement’s authors view as insufficient. First, despite calling for “responsible communication of results,” the ePPP framework needs clearer guidelines detailing how to go about this. Second, the framework should add measures to improve the transparency and inclusivity of the review and approval process through including more stakeholders, ensuring there are no conflicts of interest, and making approval deliberations publicly available. Finally, the statement calls for a clear definition of mandatory biosafety and biosecurity standards and manners of implementation. 
• Expand the Reach of ePPP Research: The statement notes that current ePPP guidance is only binding to HHS-funded research, and recommends that its reach be expanded to regulate all USG-funded research, as well as research funded by private institutions or philanthropies. In addition, the statement recommends outreach to international governments to encourage the implementation of similar policies. 
• Revise U.S. DURC Policy: The statement recommends expanding the DURC guidance to cover all human pathogens, and to add additional experiment types. The statement also calls for more explicit direction with regard to what risks researchers should consider and work to mitigate.

These recommendations provide a useful starting point for clarifying and strengthening the United States’ regulation of ePPP research and DURC more broadly. While some scientists and stakeholders are concerned that creating stricter guidance will impede life sciences research, the biosecurity and biosafety risks of weak DURC policies are too great to ignore. The NSABB’s review will ideally come to a consensus that ensures DURC is regulated appropriately without preventing scientists from conducting valuable work to the safest and most secure extent possible.