Stanford University Dual Use Research of Concern in the Life Sciences Understanding the Issues and Procedures

This training will provide the following information: An understanding of the issues associated with Dual Use Research in the life sciences A framework for the requirements of both entities and individuals under Federal policies A list of key responsibilities for Stanford University and its researchers A process to ensure compliance regarding Dual Use Research of Concern

Dual Use Research (DUR) vs Dual Use Research of Concern (DURC) Research conducted for legitimate purposes that generates information, technologies, and/or products that can be utilized for both benevolent and harmful purposes A subset of research, as defined by the Federal government, that has the greatest potential for generating information that could be readily misused to threaten public health and national security has been termed “dual use research of concern” or DURC The United States Government (USG) is presently limiting the scope of DURC policies to a subset of 15 biological agents and toxins that are considered Select Agents and are regulated by the US Department of Health and Human Services and the U.S. Department of Agriculture. Additionally there are 7 categories of experiments that come under DURC.

Does research directly involve one or more of 15 agents or toxins listed in the Policy? Biological Agents*/toxins* and Experimental Effects that are covered by DURC Avian influenza virus (highly pathogenic) Bacillus anthracis Botulinum neurotoxin Burkholderia mallei Burkholderia pseudomallei Ebola virus Foot-and-mouth disease virus Francisella tularensis Marburg virus Reconstructed 1918 Influenza virus Rinderpest virus Toxin-producing strains of Clostridium botulinum Variola major virus Variola minor virus Yersinia pestis * Only attenuated strains of the agents that are excluded from the Select Agent list and inactive forms of botulinum neurotoxin are exempt from these regulations. For additional information contact Stanford Biosafety (esegal@Stanford.edu, 650.725.1473)

Does research directly involve one or more of 15 agents or toxins listed in the Policy? Does research aim to or is reasonably predicted to produce one of seven listed experimental effects? Biological Agents/toxins and Experimental Effects that are covered by DURC Yes Categories of experiments: Enhances the harmful consequences of the agent or toxin; Disrupts immunity or the effectiveness of an immunization against the agent or toxin without clinical or agricultural justification; Confers to the agent or toxin resistance to clinically or agriculturally useful prophylactic or therapeutic interventions against that agent or toxin or facilitates their ability to evade detection methodologies; Increases the stability, transmissibility, or the ability to disseminate the agent or toxin; Alters the host range or tropism of the agent or toxin; Enhances the susceptibility of a host population to the agent or toxin; or Generates or reconstitutes an eradicated or extinct agent or toxin listed on previous slide.

Research That A PI Thinks May Meet the Definition of DURC Does research directly involve one or more of 15 agents or toxins listed in the Policy? Does research aim to or reasonably predicted to produce one of seven listed experimental effects? Does research meet definition of DURC? Research That A PI Thinks May Meet the Definition of DURC Yes Yes An Institutional Review Entity (IRE, at Stanford it is the Administrative Panel on Biosafety (APB)) must identify the risks associated with the potential misuse of the information, technologies, or products that may be generated. Included in this assessment are the following: The ways in which knowledge, information, technologies, or products from the research could be misused to harm public health and safety, agriculture, plants, animals, the environment, materiel, or national security. The ease with which the knowledge, information, technologies, or products might be misused and the feasibility of such misuse. The magnitude, nature, and scope of the potential consequences of misuse.

1+1≠ 2 Is it DURC? There may be instances in which an Institutional Review Entity determines that the research: (a) directly involves nonattenuated forms of one or more of the listed agents, and (b) produces, aims to produce, or is reasonably anticipated to produce one or more of the listed experimental effects However the IRE also determines that the research in question does not meet the definition of DURC (and is therefore not subject to additional oversight). In this case the PI must notify the IRE in the future if, for whatever reason (e.g., changes in the research, new discoveries), he or she believes that the research should be reconsidered by the IRE because it may now meet the definition of DURC. The IRE will review the research, including any new information, and determine whether the research is DURC.

Research not currently covered by DURC The use of any of the listed agents in attenuated forms; The use of the genes from any of the listed agents; In silico experiments (e.g., modeling experiments, bioinformatics approaches) involving the biology of the listed agents; or Research related to the public, animal, and agricultural health impact of any of the listed agents (e.g., modeling the effects of a toxin, developing new methods to deliver a vaccine, developing surveillance mechanisms for a listed agent).

Research Subject to DURC Policies Does research directly involve one or more of 15 agents or toxins listed in the Policy? Does research aim to or reasonably predicted to produce one of seven listed experimental effects? Does research meet definition of DURC? Requires additional Federal and local oversight and risk mitigation strategies to address dual use concerns Yes Yes Yes

Overview of the Process for Institutional DURC Oversight PI PI identifies research that involves any of the 15 listed agents; Submits research protocol via eProtocol to the Stanford University Administrative Panel on Biosafety (APB) APB Determines whether the research involves any of the 7 experimental effects; If so, conducts a risk assessment to determine whether the research is DURC; and If so, weighs the risks and benefits and develops a draft risk mitigation plan Government USG funding agency finalizes and approves risk mitigation plan APB Institution implements approved risk mitigation plan and provides ongoing oversight PI conducts and communicates research according to risk mitigation plan PI PPI I

Institutional Oversight DURC Oversight: A Shared Responsibility Throughout the Research Continuum Federal Oversight Provides advice and guidance on communicating findings Reviews progress reports for DURC Project Conceptualization Considers DURC aspects when designing project Funding Decision Implements approved risk mitigation plan Research Conduct Conduct ongoing institutional DURC reviews Research Communication Identifies DURC, develops risk mitigation plan with institution Institutional Oversight Communicates findings responsibly

Investigator Responsibilities Contact Stanford Biosafety if you will be using a Biological Agent/Toxin identified as covered under DURC Be knowledgeable about and comply with all institutional and Federal policies and requirements for oversight of DURC Conduct DURC in accordance with the risk mitigation plan Continue to assess research to determine if, at any time, the research becomes subject to the policy Ensure that laboratory personnel conducting research have received education and training on DURC Communicate DURC in a responsible manner, throughout the research process, not only at the point of publication and is in compliance with the risk mitigation plan approved by the appropriate Federal funding agency

Resources NIH Dual Use Research of Concern DURC A Companion Guide DURC Case Studies Dual Use US Dept of Health & Human Services US Policy for Institutional Oversight of DURC US Policy for Oversight of DURC Stanford University Biosafety Program Ellyn Segal, Ph.D., Biosafety Manager esegal@stanford.edu Environmental Health & Safety 650.723.0448