Debate over controversial "gain-of-function" (GOF) studies on H5N1 flu and other pathogens took a major step forward today, with experts for the first time addressing three key documents that came out of a federal advisory group's charge by the Obama administration to help guide funding policies.
In October 2014 the White House announced a pause on federally funded GOF research, which involves studies that enhance the pathogenicity, transmissibility, or host range of a pathogen to better understand it. The White House also asked the National Institutes of Health's National Science Advisory Board for Biosecurity (NSABB) to come up with recommendations to help federal officials weigh funding decisions.
Since then, the group fleshed out a risk-benefit framework for assessing such studies and awarded a contract for the full analysis to Gryphon Scientific. In December, Gryphon delivered a more than 1,000 page risk-benefit analysis, designed to guide NSABB workgroup recommendations.
On the first day of a 2-day meeting, expert panels today responded to Gryphon's risk-benefit assessment, addressed the ethics report that it commissioned, and discussed wider policy issues related to GOF research.
Acknowledging that the lengthy risk-benefit assessment was released shortly before the holidays, compressing the time the scientific community had to read and weigh in on the report in advance of the meeting, NSABB members and federal officials emphasized several times that researchers and members of the public still have several opportunities to comment. They encouraged people to send the group feedback and attend the National Academies forum on GOF research in March.
Workgroup previews recommendations
Though the NSABB will hold a full panel discussion tomorrow on the working group's draft recommendations for funding GOF studies, Joseph Kanabrocki, PhD, who led the team, gave the group a brief overview today. He is associate vice-president for research safety and associate professor of microbiology at the University of Chicago. The working group's 70-page draft report, dated Dec 23, is posted on the NSABB's Web site.
He said the report contains five key findings: (1) only a small subset of GOF studies are risky enough to require extra oversight, (2) the US government has policy frameworks in place that can manage GOF risks when implemented effectively, (3) current policies aren't sufficient for all concerning GOF studies, (4) some studies shouldn't be conducted on ethical and public health grounds if potential risks outweigh the benefits, and (5) biosafety and biosecurity issues are international issues that need global attention.
Kanabrocki added that the group suggests four recommendations. One is careful review of the biosafety and biosecurity aspects of research proposals for GOF studies of the greatest concern before making funding decisions, and if funded, subject them to ongoing oversight. Another is beefing up oversight for pathogens that have less robust oversight. The group also recommended that the GOF risk-benefit profile be periodically updated and that federal officials foster a culture of lab safety not just for GOF studies, but for all pathogen research.
He said the workgroup will continue to field feedback on its draft report and is slated to present a final draft for the NSABB to consider in the spring.
Panelists respond to risk-benefit assessment
In general, experts praised the work that went into the risk-benefit analysis, but they raised several concerns. One echoed by several was the use of the 1918 pandemic virus as a comparator, because it may be less alarming than a lab-made transmissible virus or because the population may have had greater immunity to it. Some noted that seasonal flu may have been a more useful comparator.
Thomas Inglesby, MD, director of the Center for Health Security at the University of Pittsburgh Medical Center, said he thought the scope of the risk-benefit analysis was too broad, including, for example, work on vaccine viruses, which hasn't really raised concerns during the ongoing debate.
"It fuzzies the risks and benefits," he added, noting that creation of novel flu strains has been the main issue. Inglesby also said the report appears to overstate benefit claims, which he says require external validation.
He and others said they wished the report addressed in greater detail the GOF risks at the global level.
Some of the panel members said the analysis seemed weighted more toward researchers involved in GOF studies, and less toward those who mainly use alternative methods to study the viruses.
Representatives from Gryphon said they reached out to interview scientists from both areas, but got a less robust response from alternative-GOF researchers. Since the risk-benefit report was released last month, some of the scientists who are part of the Cambridge Working Group, which formed in 2014 to galvanize support for a more careful assessment of GOF studies, have been compiling their responses to the risk-benefit report online.
Ron Fouchier, PhD, whose research group published one of two H5N1 GOF papers that helped fuel the debate when it was submitted in 2011, said, in contrast, that the report's broad approach was one of its strengths, and added that it didn't adequately cover the long-term benefits of such studies. Fouchier is a researcher at Erasmus Medical Center in the Netherlands.
He said the analysis's biggest gap was that it lacks a qualitative biosafety assessment, thus glossing over biosafety enhancements at labs.
Fouchier said so far none of the viruses in GOF studies have posed risks beyond those posed by wild-type viruses.
Dan Jernigan, MD, MPH, with the National Center for Immunization and Respiratory Diseases at the US Centers for Disease Control and Prevention (CDC) said that use of a public health lens requires the risk-benefit analysis to build in some flexibility for use in an emergency setting.
Rocco Casagrande, PhD, principal investigator and managing director at Gryphon, noted that the report's focus on the United States reflects the nature of its task as determined by the NSABB. He said the use of the 1918 virus as a comparator, while it might not be ideal, helped streamline presentation of the complex analysis.
Responding to comments about the longer timeframe given for benefits as compared with risks, he said the analysis took into account the long timeline common in research and development efforts.
Experts comment on ethics report
A panel discussion also took up an ethics white paper written by Michael Selgelid, PhD, who directs the Centre for Human Bioethics at Monash University in Melbourne, Australia, and is with the World Health Organization's Collaborating Center for Bioethics. The report, first released in December, also appears on the NSABB's Web site.
In introducing the panel, NSABB member Susan Wolf, JD, an NSABB member, said, "The NSABB acknowledged early that ethics and values play an inescapably key role." She is a law professor specializing in medicine and public policy at the University of Minnesota.
Wolf said the white paper has three main parts: a review of the literature, a review of decisional frameworks for risk-benefit assessment, and a potential framework for the NSABB. She added that Selgelid's paper should serve as a springboard for even greater discussions.
Gaps in global considerations also came up in the ethics discussion. David Fidler, JD, MPhil, a law professor who specialized in international law, including global health security, at Indiana University, said both the ethics report and the working group's draft are too general. He said they offer no insights on how to apply ethical touchstones in a global context.
"We need to learn from the global controversy over the H5N1 [GOF] papers," he said.
NSABB meeting Web page
Gryphon's risk-benefit analysis
Dec 23, 2015, NSABB working group draft report
Dec 11, 2015, CIDRAP News story "GOF risk-benefit analysis unveiled ahead of NSABB debate"
Cambridge Working Group comments