Mar 26, 2012 (CIDRAP News) – The lead researcher of one of the controversial H5N1 avian influenza transmission studies in ferrets said today that he hopes scientists can resume work on the studies in about 2 weeks, after key groups have discussed the issues.
Dutch researcher Ron Fouchier, PhD, of Erasmus University, said the voluntary 60-day moratorium on lab-modified H5N1 viruses expired Mar 20 and added that researchers are waiting for national governments to release their lab biosecurity assessments. These assessments were a component of a plan stemming from a World Health Organization (WHO) meeting of technical experts in February.
Fouchier made his comments during a live episode of virologist Vincent Racaniello's "This Week in Virology" (TWiV), which was broadcast via webcast from the Society for General Microbiology conference in Dublin, Ireland. Racaniello, a virologist at Columbia University, authors Virology Blog and hosts the weekly virology podcast series.
Fouchier's group at Erasmus and a University of Wisconsin team led by Yoshihiro Kawaoka, DVM, PhD, conducted experiments that involved engineering an H5N1 virus and an H1N1-H5N1 hybrid, respectively, that were transmissible in ferrets via airborne droplets.
The studies have been accepted for publication in Science and Nature, but advisors to the US government in December recommended against publishing the full details of the studies, due to bioterrorism concerns.
When asked about the status of the research work and the publication of the studies, Fouchier said the Dutch government has reexamined lab biosecurity requirements for H5N1 transmission work and has maintained its advice that the work be done in enhanced biosafety level 3 (BSL-3) conditions. He said counterparts in the United States have completed their assessment, and though officials are still working through some details, they will likely recommend staying at the same enhanced BSL-3 level.
Fouchier said researchers are also waiting to hear feedback from two other groups. One is the US National Science Advisory Board for Biosecurity (NSABB), which will meet on Mar 29 and 30 to review the latest versions of the two manuscripts.
The other is an international scientific meeting on H5N1 research issues, which will take place Apr 3 and 4 at a Royal Society conference in London. According to the Royal Society's meeting agenda, the conference participants will include Fouchier, Kawaoka, a host of internationally recognized H5N1 researchers, representatives from the NSABB, biosecurity experts, dual-use research experts, editors from Nature and Science, along with participants from public policy, vaccine research, funding, and journalism fields.
Though researchers are waiting for all the different groups to weigh in, he said that, ultimately, the two research groups and the scientific journals have the final say on when and how the two manuscripts will be published.
The WHO H5N1 study group had also said the pauses in publication and research could help research groups explain the nature and importance of their work to the public. Fouchier told viewers today that the best way to connect with the public on the issues is at the time the papers are published so that the researchers can fully describe and defend what they did in the labs.
Fouchier said the Dutch government is investigating whether it can use export controls to block the publication of the Erasmus group's paper. "In our opinion, they cannot," he said.
In early March the Netherlands' minister of public health, welfare, and sport sent a letter to the Dutch parliament noting that an export permit is needed to share detailed information about the H5N1 virus outside of the European Union and that the government will consider health and safety risks if such a permit was requested.
Also during the webcast, Racaniello asked Fouchier to clarify confusion over the virulence of the lab-modified viruses that arose after the researcher described his experiments at a Feb 29 panel discussion hosted by the American Society for Microbiology. During that panel discussion, Fouchier said the lab-modified H5N1 wasn't highly lethal following airborne spread among ferrets, though it was deadly when inoculated in high doses into the lower respiratory tracts of the animals.
Observers who have been following the discussions closely varied over whether Fouchier's comments squared with his initial public comments about the work.
Fouchier told the audience that virulence is a tough issue to describe and needs to be clearly defined. He said the virus was virulent in ferrets that were inoculated deep within their lungs, and it was virulent in those who were sickened via the aerosol route, though they didn't die.
"There's a lot of quotes in the press that are simply wrong," he said, adding that the definition of virulence touches on other factors such as dose, immune status of the host, and previous exposure to other types of flu. Fouchier said full publication of both studies would help clarify questions scientists and observers have about virulence of the lab-modified viruses.
During today's webcast, Racaniello asked for more details about the study, but Fouchier said the NSABB asked him not to disclose details about the methods or mutations.
However, he said his group found a number of mutations in common when they sequenced the viruses that had made the jump to airborne spread. "Most of those were pretty interesting," he said, adding that some of the mutations are the same ones Kawaoka's group found, though that group took a different approach to the study. "That was a shock to me and to Yoshi," he said.
In related developments today, the European Centre for Disease Prevention and Control (ECDC) reaffirmed its Feb 29 risk assessment on the controversial H5N1 lab viruses, which supported the actions that came out of the WHO consultation, including full publication of the studies, and said it was difficult to give a full opinion on the risk without knowing all the data from the two studies.
In a new comment on its earlier risk assessment today, the ECDC said part of the reason it believes the full papers should be published is that doing so could clear up confusion that has arisen over pathogenicity and transmissibility issues and enable a better risk assessment.
It said its review of the available data suggests that the type of work requires high levels of security, but the viruses produced in the studies don't seem very transmissible or pathogenic, at least in ferrets.
"As far as we can see it from the data, neither the Rotterdam or Madison viruses will kill a ferret unless they are introduced in high doses into the lungs," the ECDC said.
It added that in the natural transmission setting, the lab-modified viruses seem to spread poorly among the animals, sickening them with the equivalent of an upper respiratory tract infection.
This appears to go against the view of the NSABB. In a Mar 2 ScienceInsider story, several NSABB members emphasized the importance of altered transmissibility with the two studies.
The ECDC said it based its impressions on limited research, a short report by Kawaoka, and two oral presentations. "This makes a strong case for full publication and the eventual lifting of the moratorium," the agency wrote.
Mar 26 TWiV broadcast archive
Royal Society H5N1 research meeting information
Mar 2 ScienceInsider story
Mar 12 CIDRAP News story "Dutch export rules could block publication of Fouchier H5N1 study"
Mar 5 CIDRAP News story "Details of H5N1 study spark queries from congressman, experts"
Feb 29 CIDRAP News story "With new data, NSABB may revisit H5N1 studies"
Mar 26 ECDC statement