Program for Institutional DURC Oversight

  1. Introduction
  2. Purpose
  3. Definitions
  4. Scope
  5. Framework for Institutional Oversight of DURC
  6. DURC Assessment and Risk Mitigation Plan
  7. Reporting
  8. Publication
  9. Export Controls and DURC
  10. Appeal and Resolution Process
  11. Annual Review and Assurance
  12. Training
  13. Resources
  14. Appendices
    1. Notification to IRE of Research that Requires Review
    2. Assessment by the IRE
    3. 30-day Reporting of Research that Meets the Scope of the Policy for Institutional DURC Oversight
    4. Template for Risk Mitigation Plan
    5. Flow Chart

I. Introduction:

Life sciences basic research is essential to the scientific advances that underpin improvements in translation to the health and safety of the public, agricultural crops and other plants, animals, the environment, materiel, and national security. Despite its value and benefits, certain types of research conducted for legitimate purposes can be utilized for malevolent ends and is known as “dual use research.” Dual use research of concern (DURC) is a subset of dual use research and is defined 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 negative consequences to public health and safety, agricultural crops and other plants, animals, the environment, material, or national security in the foreseeable future.

II. Purpose

The purpose of this program is to provide the framework for the institutional review and oversight of certain life sciences research with high-consequence pathogens and toxins.  This ensures potential DURC conducted at The University of Iowa is identified and, where appropriate, risks are mitigated.  The program has been developed to comply with the requirements of the “United States Government Policy for Institutional Oversight of Life Sciences Dual Use Research of Concern1” (US Government Policy). 

The University of Iowa’s DURC program seeks to preserve the benefits of DURC while minimizing the risk that the knowledge, information, products, or technologies generated from such research could be used in a manner that results in foreseeable harm to public health and safety, agricultural crops and other plants, animals, the environment, material, or national security.

III. Definitions

As defined within the US Government Policy:

  1. Dual use Research is research conducted for legitimate purposes that generates knowledge, information, technologies, and/or products that can be utilized for benevolent or harmful purposes.
  2. Dual use research of concern (DURC) is 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, the environment, materiel, or national security.
  3. Institution is any government agency (Federal, State or local), academic institution, corporation, company, partnership, society, association, firm, sole proprietorship, or other legal entity involved in funding, conducting, or sponsoring research.
  4. Institutional Contact for Dual Use Research (ICDUR) is designated by the institution to serve as an internal resource for issues regarding compliance with and implementation of the requirement for the oversight of DURC as well as the liaison (as necessary) between the institution and the relevant Federal funding agency.  The UI’s ICDUR is Dr. Haley Sinn, Biosafety Officer and Responsible Official.
  5. Institutional review entity (IRE) is established by the institution to execute the requirements in Section 7.2.B.i-7.2.B.v of the US Government Policy and has attributes described in Section 7.2.E. 
  6. Life sciences pertains to living organisms (e.g., microbes, human beings, animals, and plants) and their products, including all disciplines and methodologies of biology such as agricultural science, plant science, animal science, bioinformatics, genomics, proteomics, synthetic biology, environmental science, public health, modeling, engineering of living systems, and all applications of the biological sciences. The term is meant to encompass the diverse approaches to understanding life at the level of ecosystems, populations, organisms, organs, tissues, cells, and molecules.
  7. National Science Advisory Board for Biosecurity (NSABB) is a Federal advisory committee established to advise the US Government on dual use issues.

IV. Scope

Consistent with the US Government Policy, life sciences that uses one or more of the agents or toxins listed below and produces, aims to produce, or can be reasonably anticipated to produce one or more of the effects listed under “Categories of experiments” will be evaluated for DURC potential.

  1. Agents and toxins
    1. Avian influenza virus (highly pathogenic)
    2. Bacillus anthracis
    3. Botulinum neurotoxin
    4. Burkholderia mallei
    5. Burkholderia pseudomallei
    6. Ebola virus
    7. Foot-and-mouth disease virus
    8. Francisella tularensis
    9. Marburg virus
    10. Reconstructed 1918 Influenza virus
    11. Rinderpest virus
    12. Toxin-producing strains of Clostridium botulinum
    13. Variola major virus
    14. Variola minor virus
    15. Yersinia pestis
  2. Categories of experiments
    1. Enhances the harmful consequences of the agent or toxin
    2. Disrupts immunity or the effectiveness of an immunization against the agent or toxin without clinical and/or agricultural justification
    3. Confers to the agent or toxin resistance to clinically and/or agriculturally useful prophylactic or therapeutic interventions against that agent or toxin or facilitates their ability to evade detection methodologies
    4. Increases the stability, transmissibility, or the ability to disseminate the agent or toxin
    5. Alters the host range or tropism of the agent or toxin
    6. Enhances the susceptibility of a host population to the agent or toxin
    7. Generates or reconstitutes an eradicated or extinct agent or toxin listed above

V. Framework for Institutional Oversight of DURC

The University of Iowa has established a Policy for Institutional DURC Oversight that provides the framework for institutional review and oversight of DURC.

  1. The Principal Investigator (PI) is responsible for identifying research that involves nonattenuated forms of the agents listed in Section IV and assessing such projects for whether the research produces, aims to produce or can be reasonably anticipated to produce one or more of the listed experimental effects in Section IV.  A notification form (Appendix A) has been developed to assist a PI in the identification and assessment of research that requires further institutional review.
  2. The Institutional Review Entity (IRE) will review the PI’s assessment and determine whether this research meets the definition of DURC.  An assessment form (Appendix B) has been developed to assist the IRE with its assessment of research for DURC potential and further evaluate the risks and benefits of the DURC.  The IRE must notify the Federal funding agency or NIH-designated agency of its review; Appendix C has been developed to assist the IRE in this process. For any research that meets the definition of DURC, the IRE will consider the risks and anticipated benefits and develop a draft mitigation plan which will be finalized by the funding agency.

VI. DURC Assessment and Risk Mitigation Plan

Initially, the IRE will review the research to verify that it directly involves nonattenuated forms of one or more of the agents listed in Section IV using available descriptions of the research from grant proposals, project reports and other material supplied by the PI.  Research that does not involve the listed agents is not subject to additional DURC oversight. 

The second step in the IRE review process is to assess whether the research produces, aims to produce or can be reasonably anticipated to produce one or more of the listed experimental effects in Section IV using the PI’s assessment, project proposals, project reports and examples of other similar research in the literature. 

The points below will be used to assess the experimental effects of the research:

  1. Enhances the harmful consequences of the agent or toxin, e.g.,
    1. Enabling the agent or toxin to critically alter normal biological functions, inflicting damage on public health resources, materiel, and public safety.
    2. Augmenting properties such as virulence, infectivity, stability, transmissibility, or the ability of the agent or toxin to be disseminated.
      • This could entail compromising the ability to treat a disease, rendering a non-pathogenic microbe pathogenic, or making a seasonal strain of influenza virus more deadly.
      • This could also include giving out information not already in the public domain regarding routine techniques for restoring the virulence of viral stocks by back-passaging in animal hosts, identifying virulence factors through genome-wide screening or gene knockout techniques, or standard genetic manipulation to study the virulence of an organism.
  2. Disrupts immunity or the effectiveness of an immunization against the agent or toxin without clinical and/or agricultural justification.
    1. Rendering an immunization ineffective could make a host population vulnerable to the pathogenic consequences of a microbe from which the host population would have otherwise been protected or for which protection, such as a vaccine, was available.
    2. An example is the insertion of an immunosuppressive cytokine into a viral genome to render the antiviral immune response less effective, or providing information about the immunosuppressive properties of chemotherapeutic drugs for cancer or autoimmune disorders.
  3. Confers to the agent or toxin, resistance to clinically and/or agriculturally useful prophylactic or therapeutic interventions against that agent or toxin or facilitates its ability to evade detection methodologies, e.g.,
    1. Information such as conferring doxycycline resistance to Vibrio vulnificus or conferring rifampin resistance to agriculturally relevant microbes, such as Ralstonia solanacearum (a UDSA high-consequence bacterium).
  4. Alters properties of the agent or toxin in a manner that would enhance its stability, transmissibility, or the ability to disseminate a biological agent or toxin.
    1. Effective dissemination of a pathogenic agent or toxin could result in large-scale exposure and the inability to prevent or treat ensuing disease and/or damage in a host population, which could result in a significant threat to the health of the host population(s).
    2. Examples include changing genetic factors to increase transmissibility and altering the route of transmission or vector to increase the ease and effectiveness by which an agent may be transmitted; issues related to scale and intent should also be considered.
  5. Alters the host range or tropism of the agent or toxin, e.g.,
    1. Converting nonzoonotic agents into zoonotic agents, altering the tropism of viruses, and expanding the varieties of the same plant that a pathogenic agent could infect.
    2. Certain vaccine research and the development of animal models for infectious disease, which may involve alterations of the host range or tropism may not constitute DURC, e.g., the development of viruses for vaccine development whereby the procedure relies on a change in host range and results in the attenuation of human virulence.
  6. Enhances the susceptibility of a host population to the agent or toxin.
    1. Note, the distinction should be made that research applicable to this category would not alter the susceptibility of an individual host or research cohort but rather that of a host population, e.g.,
      • Creation of a stable recombinant Lactobacillus casei that could effectively block the host’s ability to synthesize an important immune signal, such as tumor necrosis factor alpha, which may directly facilitate the evasion of normal host defenses.
      • Examples that are unlikely to be considered DURC are projects on the systemic exposure to immunostimulatory and immunosuppressive DNA and its effect on host susceptibility to local inflammatory challenge, studies to develop immunosuppressive drugs for cancer or transplantation, and delivery of a small interfering ribonucleic acid (RNA) (siRNA) to a mouse that makes it hypersensitive to ionizing radiation, an infectious agent, or a toxin.
  7. Generates or reconstitutes an eradiated or extinct agent or toxin listed in Section IV, e.g.,
    1. The de novo construction of a microbial pathogen using wholly unique gene sequences or combinations of sequences that do not exist in nature and reconstitution of a pathogen that no longer exists in nature, such as the reconstruction of the 1918 pandemic influenza virus.
    2. Research that is not likely to be considered DURC includes standard experimentation that generates knockouts, mutants, reassortants, complement strains, or infectious molecular clones of viruses that are similar to naturally occurring agents.

Research that meets the scope of the US Government Policy will need to be further reviewed to determine if it meets the definition of DURC.  The IRE will identify the risks associated with the research by considering the following: (1) the ways in which the knowledge, information, technology, or products generated from the research could be misused to harm public health and safety, agriculture, plants, animals, the environment, materiel or national security; (2) the ease with which the knowledge, information, technology, or products might be misused and the feasibility of such misuse; and (3) the magnitude, nature, and scope of the potential consequences of misuse. 

The points below will be used to assess the dual use potential of the research:

  1. Could this research yield information that could be intentionally misused to threaten public health and safety or other aspects of national security?
    1. What is the nature of the information? Is it novel?
    2. Is the information applicable to other, perhaps common organisms, biologics, etc.?
    3. Could the information be directly misused to pose a threat? Does the information need to be combined with other information to pose a threat? If so, is that other information already available?
      • What is the nature of the threat that could be posed from intentional misapplication of the information and what are the potential consequences?
      • What is the potential nature (e.g., economic, agricultural, public health) and what is the potential impact of the threat?
      • What is the scope of the potential threat (e.g., how many/which people, plants, animals might be adversely affected)?
      • Are there currently countermeasures for this threat?
      • What type of technical expertise and /or physical resources would be needed to apply the information for malevolent purposes?
      • In what timeframe might the information be misused? Is there concern about immediate or near-future potential use, or is the concern about misuse in the distant future?
      • Would it require a low or high degree of technical skill and sophistication to use the dual use information for harmful purposes?
  2. Based upon these considerations, how likely (reasonably anticipated) is it that the information could pose a threat to public health and safety or other aspects of national security?
    1. If there is NO discernible potential threat, discontinue analysis, remain vigilant for DURC.
    2. If there is a discernible potential threat, then proceed with the analysis.
  3. Could this research yield information that could potentially benefit the life sciences and /or public health and safety or other aspects of national security?
    1. If so, what is the nature of that information?
      • What is the nature of the potential benefit?
      • How much of a benefit might there be?
    2. Do the potential risks outweigh the potential benefits?
      • If not, determine applicable risk management strategies.
      • If so, consider whether the research should be modified, conducted at a later time when the benefits outweigh the risks, or delayed (perhaps, in rare cases, even discontinued).
      • The risk/benefit assessment should be conducted periodically.

If the IRE determines that any DURC is identified, a draft risk mitigation plan will be developed.  The IRE will work with the USG funding agency, or NIH-designated agency, and Principal Investigator to develop a plan that applies necessary and appropriate mitigation measures.  As described in Section D of the Companion Guide, “Guidance for Responsible Communication of DURC Findings;”2 the following strategies will be used to develop the draft plan: (1) Determining whether existing biosafety and biosecurity measures are adequate; (2) Evaluating the applicability of existing countermeasures; (3) Developing a plan for communicating the findings of DURC; (4) Educating and training research staff; and (5) Developing a plan for monitoring the DURC.  See Appendix D for a template of a draft risk mitigation plan.

VII. Reporting

As outlined in the Policy for Institutional DURC Oversight, the University is responsible for notifying the US Government funding agency of the outcome of any IRE assessment and working with the funding agency to complete a draft mitigation plan, as appropriate.  Any potential concerns with the handling of DURC and implementation of the risk mitigation plan will be communicated to the US Government funding agency by the University.

VIII.  Publication

The IRE will take part in identifying and assessing risks and benefits of communicating research information that has been categorized as DURC.  The Principal Investigator will provide a general overview of the information to be communicated, including the scientific context of the information and whether or not it is already publically available.  The IRE will perform a risk benefit analysis and determine a communication plan based on their findings.  The IRE will consider the journal’s criteria for publishing such research (if any) and Section F of the Companion Guide, “Guidance for Responsible Communication of DURC Findings;”2 the IRE may also consult with the federal funding agency, as appropriate.   The plan may range from withholding information of concern, delaying publication or applying no restrictions and publishing as is.  The IRE member from the Office of Strategic Communication will inform his/her office of the pending release of information.

IX.  Export Controls and DURC

Federal export control laws restrict the export of goods, technology, related technical data, and certain services in the interest of protecting national security and domestic economy.  Export controls are accomplished primarily through the Export Administration Regulations (the "EAR," implemented by the Department of Commerce for items that have both a commercial and potential military use) and the International Traffic in Arms Regulations ("ITAR," implemented by the Department of State for military items and defense services). The Treasury Department's Office of Foreign Assets Control ("OFAC") administers and enforces economic and trade sanctions to protect foreign policy and national security goals.

The University of Iowa has designated the Division of Sponsored Programs (DSP) as the department responsible for oversight of export control compliance activities.  All DURC will be reviewed by DSP as part of the University’s export control compliance process; any research subject to export controls will be managed according to the University’s Policy.  Communication between DSP and the IRE will occur through the designated DSP staff member responsible for export control compliance and the BSO/RO.  Any export control restrictions will be taken into consideration in the development of the risk mitigation plan and managed appropriately.

X.  Appeal and Resolution Process

Institutional review and oversight of DURC will follow the US Government Policy and the University of Iowa’s Policy for Institutional DURC Oversight.  During the review process, should the PI disagree with the recommendations or risk mitigation plan developed by the IRE, the review will be referred to the Assistant Vice President for Research Compliance (Asst. VPR).  The IRE will send to the Asst. VPR a letter outlining the disagreement between the PI and IRE.  The Asst. VPR may appoint an ad hoc panel of experts to review the disputed matter; outside experts, including security experts and NSABB, may also be consulted prior to determining the course of action.   

XI.  Annual Review and Assurance

On an annual basis, the IRE will review all active risk mitigation plans to reevaluate whether the research continues to meet the definition of DURC and where appropriate, to ensure the plans continue to manage any risks associated with DURC.

The IRE will communicate with the PI to ensure the research still directly involves a non-attenuated form of a listed agent or toxin and still produces, aims to produce, or can be reasonably anticipated to produce one or more of the experimental effects.  Through this communication, the IRE will reevaluate whether the research meets the definition of DURC; if the research project is no longer subject to DURC oversight, the University will notify the appropriate funding agency within 30 calendar days.

If the research project continues to meet the definition of DURC, the IRE will review the risk mitigation plan.  The IRE will reconsider the potential risks associated with the research project in order to ensure the risk mitigation plan continues to adequately address the risks.  Any updates or modifications to the plan will be communicated by the University to the funding agency within 30 calendar days for final approval.  The IRE will ensure the risk mitigation plan, and any modifications, are implemented by the PI.

The IRE will also monitor emerging findings for DURC potential and will ensure any emerging DURC risks is fully examined by the PI and the committee following the standard review process.

XII.  Training

The University of Iowa’s Program for DURC Oversight will provide training for research staff and IRE members.  The training will be based on the research carried out and the responsibilities of the individual. 

  1. General Awareness Training
    1. All research staff will receive general awareness training for DURC through completion of required training courses administered by the Environmental Health & Safety Office (EHS).
  2. Select Agent Registered Investigators
    1. All investigators registered with the Select Agent Program will receive training designed to provide a general framework for DURC oversight.  Training will allow research staff to:
      • Recognize and understand what types of research could be considered DURC;
      • Become aware of the listed agents and toxins in the US Government Policy;
      • Understand the categories of experiments in the US Government Policy; and
      • Understand potential limitations of such research on publication activities.
  3. Investigators engaged in DURC
    1. Individuals engaged in research considered DUR or DURC will receive in depth training to ensure they understand the policy and procedures governing the conduct of such research. In addition to the training required for select agent registered individuals, training will address:
      • The need for continued monitoring of DUR, due diligence, and recognizing when research might become DURC;
      • The University of Iowa’s Policy and Program documents for Institutional DURC Oversight; and
      • Relevant documents from NSABB.
  4. IRE Committee
    1. All new members will meet with the IRE-Chair and BSO/RO and will receive training on the US Government Policy, the University of Iowa’s Policy for Institutional DURC Oversight, the University’s Program for Institutional DURC Oversight and any other relevant resources, such as the NSABB’s “Life Scientist: Core Responsibilities Regarding Dual Use Research of Concern.”
    2. Ongoing training for members will consist of relevant articles and case studies discussed at IRE meetings.

XIII.  Resources

  1. United States Government Policy for Institutional Oversight of Life Sciences Dual Use Research of Concern
  2. Tools for the Identification, Assessment, Management, and Responsible Communication of Dual Use Research of Concern, A Companion Guide.  National Institutes of Health, September 2014.
  3. The NSABB website has a number of tools to aid in understanding and identifying DURC, the risk assessment, etc. The website is http://www.phe.gov/s3/dualuse/Pages/default.aspx.

XIV.  Appendices

  1. Notification to IRE of Research that Requires Review
  2. Assessment by the IRE
  3. 30-day Reporting of Research that Meets the Scope of the Policy for Institutional DURC Oversight
  4. Template for Risk Mitigation Plan
  5. Flow Chart