H5N1 researchers question proposed HHS funding framework

Lisa Schnirring

Dec 17, 2012 (CIDRAP News) – Federal health officials are in the midst of crafting a framework for funding H5N1 avian influenza gain-of-function studies, and today at a workshop they heard varied feedback from researchers, biosecurity experts, and others.

The 2-day workshop, held at the National Institutes of Health (NIH), is the latest chapter in an intense scientific controversy that was triggered by the publication of two recent studies involving lab-engineered H5N1 strains that showed signs of being transmissible in mammals.

Publishing the details of the experiments in two scientific journals in May and June sparked bioterror concerns, and the existence of the engineered strains in labs raised fears about an accidental or intentional release. Early in the debate the H5N1 community agreed to a 60-day research moratorium, which has now tarried for almost a year.

The global scientific community is closely watching the framework discussions, because the US Department of Health and Human Services (HHS) is one of the world's biggest funders of H5N1 research, including the two studies that sparked the controversy. Studies on H5N1 are considered a key pandemic preparedness step, and research findings have been used to help governments guide the development of vaccine and antiviral countermeasures.

Harvey Fineberg, MD, PhD, president of the Institute of Medicine (IOM), moderated the morning workshop sessions. He said the goal of the meeting isn't to reach consensus, but to share and hear points of view on the framework and issues related to H5N1 research.

NIH Director Anthony Fauci, MD, told the group that the H5N1 gain-of-function studies only make up a minor but important part of the institute's H5N1 research portfolio, but it has triggered a very important discussion. "There are some disagreements about the scientific and public health value," he said, adding later that the framework isn't designed to be a mandate, but rather a process for how to weigh the risks earlier in the research proposal process.

The HHS meeting was designed to provoke discussions among scientists and health officials from other countries about the risks and benefits of gain-of-function H5N1 studies, and federal officials acknowledged that there may be important risks associated with not doing the studies.

Ron Fouchier, PhD, whose research group at Erasmus University in the Netherlands published one of the two controversial H5N1 studies, said more work needs to be done to determine if the mutations could drive other H5N1 lineages to go airborne. The two studies looked at only limited Indonesian and Vietnamese clades.

Ilaria Capua, DVM, PhD, director at the division of comparative biomedical sciences at the Institute Zooprofilattico Sperimentale delle Venezie in Legnaro, Italy, urged attendees to consider the long-term implications of H5N1 research policies.

She said her lab is in a position to observe what's happening with the virus in Egypt, where social unrest has already caused destruction at one environmental health lab. In the next 20 years, she said, hundreds of labs could have the capacity to do reverse genetics work, with some likely in countries that will face political turmoil.

Some US government officials said the pause in H5N1 research is putting a damper on preparedness activities. Nancy Cox, MD, director of the influenza division at the US Centers for Disease Control and Prevention (CDC), said that scientists look at mutation patterns to assess if current H5N1 vaccine viruses can be improved. "We've had to put our work on hold. There is a tremendous amount of work that has simply not been able to take place," she said.

The HHS first aired the draft criteria before the National Science Advisory Board for Biosecurity (NSABB) in late November, which raised concerns from some flu researchers that the plan could block funding for many potentially useful studies, though other experts hailed it as a productive next step in addressing concerns about the lab-modified viruses.

In introducing the draft to workshop participants, Amy Patterson, MD, associate director for science policy at the NIH, said the goal of the framework is to allow officials to take a second look at the H5N1 research proposals. She emphasized several times that the specifics aren't set in stone and that the HHS is looking for detailed feedback from scientists, biosafey and biosecurity experts, international health officials, and members of the public. "Every aspect of this is on the table," she said.

The plan includes seven criteria for assessing if the proposal is acceptable for HHS funding and a mechanism for submitting some proposals to a more detailed department-level review. Patterson said federal health officials are already aware that some of the criteria wording is controversial, especially one that would bar research on H5N1 changes that wouldn't likely occur in nature. She also added that scientists have already aired some concerns about interpreting some of the framework's wording, such as, for example, the term "foreseeable future."

"I think it's fair to say there's a world of judgment inherent in each of the words in the criteria," she said, adding that she hoped workshop participants and other commenters will flag any risks that aren't included in the draft framework.

Marianne Donker, PhD director of public health with the ministry of health, welfare, and sport, at The Hague in the Netherlands, called the HHS proposal a courageous first step that is necessary to start discussions on H5N1 research issues. She said the Dutch government is developing a biosecurity regime that would apply to all dual-use research of concern (DURC, which applies to research that could be used for good or bad purposes), not just ones that focus on H5N1.

Yoshihiro Kawaoka, DVM, PhD, who led the other controversial research study, said that, in principal, the HHS framework should serve as a useful guide, but his view is that it's too inclusive to be functional. As written, the framework might require too many proposals to be sent for department review, which could bog down the flow of research information about the virus.

"For those of us who do basic research, progress is incremental and builds on the results of knowledge," he said.

Kawaoka, of the University of Wisconsin, suggested that the criteria focus on studies that lead to harmful H5N1 viruses that don't exist in nature.

Tom Inglesby, MD, agreed that basic research has yielded benefits, but he said it isn't enough to justify the risks. Only a small fraction of viruses in the wild are sequenced, and Inglesby said it's not clear what specific and different actions countries would take if surveillance found a strain that matched a lab-engineered virus. He added that the benefits for vaccine development lack concrete arguments to make the case.

Inglesby, chief executive officer and director for the Center for Biosecurity at the University of Pittsburgh Medical Center, called the proposed criteria a good step forward, but said until experts agree on what the risks are, the research moratorium should continue.

The workshop continues tomorrow with a discussion with experts to identify the conditions, if any, under which H5N1 gain-of-function research should take place. The HHS will post a summary and video of the meeting at a later date for those who weren't able to attend, and it is encouraging people to submit written comments by Jan 10, 2013.