October 01, 2015
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ID, clinical community hold key role in gain-of-function research debate

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In a pair of articles recently published in The Journal of Infectious Diseases, experts highlighted key areas of the ongoing gain-of-function research debate and argued that its relevance to clinical practice justifies input from the infectious disease and practitioner community.

“Gain-of-function (GOF) research typically involves mutations that confer altered functionality of a protein or other molecule,” Andy Kilianski, PhD, of the biosciences division of the Edgewood Chemical Biological Center in Maryland, and colleagues wrote. “These types of mutations have been used as powerful tools to understand basic bacterial and viral biology and pathogen-host interactions.

“In recent years a public discussion has surfaced, centering on the application of GOF research to highly pathogenic and potentially lethal viruses. Despite the emergence of this public dialogue, much of it has been steered by members of the microbiology and policy communities. There remains room for additional input from clinical and public health practitioners, who are often the end users of the products GOF research yields.”

Discussions concerning the safety and benefits of GOF began in 2010 with studies on the transmission dynamics of highly pathogenic avian influenza H5N1, Kilianski and colleagues wrote. Since then, a moratorium on GOF research of concerned was issued by the White House Office of Science and Technology Policy and the U.S. Department of Health and Human Services on Oct. 17, 2014, and has seen few exceptions. A deliberative review process led by the National Science Advisory Board for Biosecurity (NSABB) also was formed and is currently in progress. Its goals are to determine the clinical applications of this research, weigh them against the risks for misuse or accidental pathogen release, and establish recommendations for the assessment of future study.

Benefits of GOF research are numerous, according to Kilianski and colleagues, and include the development of animal model adaptation, vaccine development, disease surveillance and the prevention of pathogenic mutations resulting from exposure to experimental therapeutics. While these arguments continue to be examined by NSABB, the input of infectious disease clinicians is crucial to the debate, they wrote.

“Recent outbreaks of Ebola virus, [Middle East respiratory syndrome, or MERS, coronavirus] and pandemic influenza … continue to demonstrate that medical and public health readiness for emerging infections is not always optimal and could benefit from more research and development,” Kilianski and colleagues wrote. “GOF research plays a significant role in ensuring that clinicians have the tools they need to respond to infectious disease outbreaks. Therefore, the clinical community is directly affected by policy decisions on what types of research are and are not allowed to continue.”

David Relman

David A. Relman

The call for clinician input was echoed by members of the Infectious Diseases Society of America. In an editorial also published in The Journal of Infectious Diseases, David A. Relman, MD, of Stanford University School of Medicine, and colleagues said that leaders in the field have an “ethical responsibility” to appropriately identify experiments whose benefits outweigh risks to public safety.

In addition, they recapped a series of recommendations submitted by an IDSA working group to NSABB on Aug. 10, which included:

  • focusing on GOF experiments of special concern;
  • addressing the uncertainty in estimating both risk and benefit;
  • seeking a wide breadth of expertise to aid in the results-based accountability process
  • accounting for the impact on public perception of science;
  • accounting for the impact of new GOF frameworks on the course of science; and
  • considering recommendations on increasing GOF research safety.

“IDSA appreciates the NSABB’s efforts on the GOF debate and its willingness to engage with the public as it develops its final recommendations,” Relman and colleagues wrote. “We look forward to working with the public as well as the [U.S. government] to ensure that GOF research of concern is conducted appropriately, and only when the risk is outweighed by the benefit to public health.” – by Dave Muoio

Disclosures: Kilianski and Relman report no relevant financial disclosures. Please see the full editorial for a list of all other authors’ relevant financial disclosures.