Dual Use Research of Concern (DURC) and Pathogens with Enhanced Pandemic Potential (PEPP)

Pardon our progress: This page is under construction as the UMB biosafety team prepares for implementation of the US Government Policy for Oversight of DURC and PEPP, which is set to go into effect on May 6, 2025. 

Jump to: Introduction, What is Category 1 and Category 2 Research?, Principal Investigator Responsibilities, Resources

Introduction

Life sciences research improves and saves lives every day. However, in some cases, this research yields materials or knowledge that can be directly misapplied for nefarious purposes.

One classic, real-life example of this is experimentally increasing the ability of some avian influenza viruses to be transmitted among mammals. While this experiment could provide valuable insight in terms of public health (use 1), it could arguably provide a blueprint for the creation of a biological weapon (use 2). Thus, these types of experiments are called “dual use research.” 

For an interesting introduction to the topic of dual use research, watch the recommended video below from the NIH.

What is Category 1 and Category 2 Research?

In the 2024 "US Government Policy for Oversight of Dual Use Research of Concern and Pathogens with Enhanced Pandemic Potential" (USG Policy), two categories of the most concerning research are defined as:

  • Category 1, also referred to as Dual Use Research of Concern (DURC), and
  • Category 2, also referred to Pathogen with Enhanced Pandemic Potential (PEPP) research.

To qualify for each category under the policy, a series of three conditions must be met, which are outlined in the table below.

  Category 1 Research - DURC Category 2 Research - PEPP
Condition 1: Agents and/or toxins involved in research
  1. A Select Agent or Toxin (list), including select toxins at exempt quantities.
  2. A Risk Group 4 pathogen as listed in Appendix B of the NIH Guidelines.
  3. A Risk Group 3 pathogen as listed in Appendix B of the NIH Guidelines with the exceptions of:
    • Human Immunodeficiency Virus (HIV),
    • Human T-Lymphotropic Virus (HTLV),
    • Simian Immunodeficiency Virus (SIV),
    • Mycobacterium tuberculosis,
    • Mycobacterium bovis,
    • Clade II of Monkeypox virus,
    • Vesicular Stomatitis Virus,
    • Coccidioides immitis,
    • Coccidioides posadasii,
    • Histoplasma capsulatum, and
    • Histoplasma capsulatum var. duboisii.
  1. Any pathogen that is likely capable of wide and uncontrollable spread in a human population and would likely cause moderate to severe disease and/or mortality, also referred to as a Pathogen with Pandemic Potential (PPP).
  2. Any pathogen that is modified in such a way that is reasonably anticipated to result in a PPP.
Condition 2: Experimental outcomes of research
  1. Increase transmissibility of a pathogen within or between host species.
  2. Increase the virulence of a pathogen or convey virulence to a non-pathogen.
  3. Increase the toxicity of a known toxin or produce a novel toxin.
  4. Increase the stability of a pathogen or toxin in the environment, or increase the ability to disseminate a pathogen or toxin.
  5. Alter the host range or tropism of a pathogen or toxin.
  6. Decrease the ability for a human or veterinary pathogen or toxin to be detected using standard diagnostic or analytical methods.
  7. Increase resistance of a pathogen or toxin to clinical and/or veterinary prophylactic or therapeutic interventions.
  8. Alter a human or veterinary pathogen or toxin to disrupt the effectiveness of preexisting immunity, via immunization or natural infection, against the pathogen or toxin.
  9. Enhance the susceptibility of a host population to a pathogen or toxin.
  1. Enhance transmissibility of the pathogen in humans.
  2. Enhance the virulence of the pathogen in humans.
  3. Enhance the immune evasion of the pathogen in humans, such as by modifying the pathogen to disrupt the effectiveness of pre-existing immunity via immunization or natural infection.
  4. Generate, use, reconstitute, or transfer an eradicated or extinct PPP, or a previously identified PEPP.
Condition 3: Research meets definition "Based on current understanding, the research can be reasonably anticipated to provide, or does provide, knowledge, information, products, or technologies that could be misapplied to do harm with no — or only minor — modification to pose a significant threat with potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security." "The research can be reasonably anticipated to result in the development, use, or transfer of a PEPP or an eradicated or extinct PPP that may pose a significant threat to public health, the capacity of health systems to function, or national security."

    While the three conditions must all be met to qualify as Category 1 or 2 Research, investigators should keep in mind the dual use potential of all of their work and responsibly conduct and communicate research accordingly.

    Institutional responsibilities under the USG Policy are outlined in the Institutional Biosafety Committee (IBC) Charter. In summary:

      • The IBC will work to identify proposals involving agents and/or toxins under the purview of the USG Policy (condition 1). This includes identification of agents as PPP for Category 2 Research.
      • If condition 1 is met for Category 1 and/or Category 2 Research, the IBC will convene a separate, stand alone meeting as the Institutional Review Entity (IRE). The IRE will assess a proposal for the associated experimental outcomes (condition 2) and definitions (condition 3) in order to identify Category 1 and/or Category 2 Research. 
      • Once a protocol is identified as Category 1 and/or Category 2 Research, the IRE will form a DURC/PEPP Subcommittee. This subcommittee will include ad hoc members that provide additional expertise and will work with a Principal Investigator to draft a risk-benefit analysis and risk mitigation plan. If a project is federally funded, it is the funding agency that must ultimately approve the risk mitigation plan. 
      • Once a Category 1 and/or Category 2 Research project is approved and begins, the DURC/PEPP Subcommittee will meet at least semiannually for review, evaluation, assessment, and if needed, clarification or confirmation.

    Principal Investigator Responsibilities

    1. Be knowledgeable about and comply with all UMB and US Government policies, requirements, and regulations for the oversight of biological agent and toxin research.

    2. Assess your research at the proposal stage, and continuously throughout the research lifecycle to identify whether there is research reasonably anticipated to be within the scope of Category 1 and/or Category 2 Research (see table above for conditions). Following the identification of potential Category 1 or Category 2 Research, notify the federal funding agency (if applicable) and UMB biosafety staff (x6-7055) as soon as possible.

    3. Submit an IBC protocol for any research involving infectious agents, recombinant or synthetic nucleic acid molecules, select toxins (at any quantity), and/or human materials using the online CICERO system. As part of the normal IBC registration process, all protocols are reviewed for potential Category 1 or Category 2 Research and referred to the IRE as needed.

    4. For Category 1 and/or Category 2 Research, work with the IRE and/or DURC/PEPP Subcommittee to assess the risks and benefits of the proposed research and draft a risk mitigation plan. 

      • If research is being proposed as part of a new funding proposal, the federal funding agency (if applicable) will require submission of the risk-benefit assessment and draft risk mitigation plan once the proposal is under consideration for funding. Agencies will give a 30-day deadline, so it is highly recommended that you submit potential Category 1 or Category 2 Research proposals to the IBC as early as possible and not wait until you are notified that the documents are needed.
      • If the research is being funded under an existing funding mechanism, but has not yet been reviewed by the applicable federal funding agency, then submit the risk-benefit assessment and draft mitigation plan to the federal funding agency for approval before conducting such work.
      • If research is first identified as potentially within scope of Category 1 or Category 2 during the course of experimentation, halt further work and notify UMB biosafety staff (x6-7055), who will help you navigate the requirements of a risk-benefit assessment and risk-mitigation plan that will need to be approved before work may continue.

    5. Conduct any Category 1 and Category 2 Research in accordance with the provisions identified in the approved risk mitigation plan.

    6. Provide semiannual progress reports for Category 1 and/or Category 2 to the IRE/DURC Subcommittee and as requested by the federal funding agency (if applicable) for review, evaluation, assessment, and if needed, clarification or confirmation. 

    7. Ensure that laboratory personnel (i.e., those under the supervision of laboratory leadership, including but not limited to graduate students, postdoctoral fellows, research technicians, laboratory staff, and visiting scientists) conducting life sciences research within the scope of the USG Policy have received and maintain education and training on all research oversight policies and processes and demonstrated competency.

    8. Communicate Category 1 and Category 2 Research in a responsible manner. Communication of research and research findings is an essential activity for all researchers and occurs throughout the research process, not only at the point of publication. When researchers are planning to communicate Category 1 and/or Category 2 Research results, it is their duty to ensure that it is done in a responsible manner, and follows any measures outlined in the risk mitigation plan approved by the IRE and (if applicable) the federal funding agency. 

    Resources

    Contact the Biosafety Officer

    Definitions and Abbreviations ▾

    • Dual use research - Research conducted for legitimate purposes that generates knowledge, information, technologies, and/or products that can be utilized for benevolent or harmful purposes.
    • Dual Use Research of Concern (DURC) - Life sciences research that, based on current understanding, can be reasonably anticipated to provide knowledge, information, products, or technologies that could be misapplied to do harm with no, or only minor, modification to pose a significant threat with potential consequences to public health and safety, agricultural crops and other plants, animals, the environment, materiel, or national security. DURC aligns with Category 1 Research.
    • Gain of Function (GOF) Research - Experiments in which a microorganism is changed, resulting in the acquisition of new, or an enhancement of existing, biological phenotypes. Note that while GOF is a term that still may be occasionally used in the context of dual use research, it has largely been superseded by the terms PEPP and DURC.
    • Institutional Contact for Dual Use Research (ICDUR) - The official designated by the research institution to serve as an internal resource for application of this Policy as well as the liaison (as necessary) between the institution and the relevant federal funding agency.
    • Institutional Review Entity (IRE) - The entity established by the research institution to execute the institutional oversight responsibilities for Category 1 and Category 2 Research as described in the USG Policy.
    • Pathogen with Enhanced Pandemic Potential (PEPP) - A type of pathogen with pandemic potential (PPP) resulting from experiments that enhance a pathogen’s transmissibility or virulence, or disrupt the effectiveness of pre-existing immunity, regardless of its progenitor agent, such that it may pose a significant threat to public health, the capacity of health systems to function, or national security. Wild-type pathogens that are circulating in or have been recovered from nature are not PEPPs, but may be considered PPPs because of their pandemic potential. PEPP aligns with Category 2 Research.
    • Pathogen with Pandemic Potential (PPP) - A pathogen that is likely capable of wide and uncontrollable spread in a human population and would likely cause moderate to severe disease and/or mortality in humans.11