Research moratorium on modified H5N1 viruses ends

Jan 23, 2013 (CIDRAP News) – A year-long voluntary moratorium on research involving transmissible H5N1 avian flu viruses ended today with a letter from a group of scientists that supports resuming the work in countries that have addressed the biosafety issues involved.

Today's letter, endorsed by 40 scientists who signed on to the voluntary moratorium last year, appeared in the journals Science and Nature. The research pause was designed to allow countries and the scientific community to discuss biosecurity and biosafety issues that were raised by the publication of two controversial H5N1 papers, one from a group in the Netherlands led by Ron Fouchier, PhD, and the other from a team at the University of Wisconsin led by Yoshihiro Kawaoka, DVM, PhD.

The scientists wrote that the moratorium allowed the community to explain the public health benefits of the transmission studies, to describe the systems that are in place to protect researchers and the public, and to allow organizations and governments to review their policies regarding the experiments.

"Thus acknowledging that the aims of the voluntary moratorium have been met in some countries and are close to being met in others, we declare an end to the voluntary moratorium on avian flu transmission studies," they wrote. The moratorium was originally planned to last 60 days.

Three of the researchers who signed the letter—Fouchier, Kawaoka, and Richard Webby, PhD, from St. Jude Children's Research Hospital in Memphis—spoke about the end of the research moratorium today at a media telebriefing sponsored by the American Association for the Advancement of Science (AAAS), the publisher of Science.

Kawaoka said the research work needs to resume, because it has important public health benefits, such as providing more clues about what it would take for the H5N1 virus to become more transmissible in mammals. "We understand the risk, and we take every precaution," he said. "The benefit outweighs the risks. That is why we need to resume."

Many countries have reviewed their oversight of H5N1 research issues, so the need for the moratorium has passed, said Webby.

The researchers said the number of countries in which H5N1 transmission studies take place is limited, and it's not entirely clear which ones are ready to resume work. They said the list includes the Netherlands, European Union countries in principle, and China. Canada has already said H5N1 transmission work can take place under biosafety level 4 (BSL-4) conditions.

Two holdouts are Japan, which is still reviewing its policies, according to Kawaoka, and the United States, which is still reviewing the H5N1 virus' select agent level and finalizing guidelines for funding gain-of-function H5N1 studies.

US plan 'weeks' away
The fact that work can't yet resume in the United States is notable, because its National Institutes of Health (NIH) funds many H5N1 research studies, including the ones by Fouchier and Kawaoka that sparked the debate, which originally focused on the potential biosecurity risk of publishing sensitive data from the studies in scientific journals.

Fouchier told reporters that the group of researchers didn't wait for the United States to take its final actions before ending the moratorium, because it's not clear how long it will take.

In October the US Department of Health and Human Services (HHS) asked the public to comment on whether H5N1 should be designated as an HHS special agent, meaning that labs handling it would have to register with the agency and meet special security and personnel screening and training requirements.

The comment period was slated to end on Jan 31, but Jason McDonald, a spokesman for the US Centers for Disease Control and Prevention (CDC), told CIDRAP News that the CDC has submitted a notice to the Federal Register that would extend the period another 30 days to allow more public comment.

He added that the CDC has no target set for a decision.

Anthony Fauci, MD, who directs the NIH's National Institute of Allergy and Infectious Diseases (NIAID), told CIDRAP News that the NIH has revised its draft guidance for funding H5N1 avian influenza research based on feedback it received at a conference in December and public comments it received through Jan 10.

He said NIH has forwarded the revised document to the HHS, which will finalize the work.

Though Fauci said there is not an exact timetable for the final guidance, he said he expects that it will be released within several weeks rather than several months.

Future research goals
At today's media briefing, the three researchers reflected on the lessons learned during the moratorium and outlined some of the key next steps with the research. Fouchier said some of his H5N1 work, the part not funded by NIH, will resume over the next few weeks as soon as lab preparations are in place. Kawaoka said his work is stalled until US agencies finalize their guidelines.

Webby said a major lesson is the need to discuss the importance of the research earlier in the process. "That's our job, to highlight the benefits, and the biggest lesson is that we can do better," he said.

Fouchier added that the H5N1 controversy and moratorium have opened up a more general discussion of dual-use research (which can be used for good or bad intents) that is ongoing and will yield future benefits. He pointed to a World Health Organization (WHO) conference last February that focused on the risks and benefits of publishing results of the two transmission studies, and he added that the group will soon host a wider dual-use research discussion.

Gregory Hartl, a spokesman for the WHO, told CIDRAP News that the meeting will include H5N1 as well as other dual-use issues and will take place Feb 26 through 28.

Fouchier said he and his research team, which already found that five to nine mutations were sufficient to make the H5N1 virus they tested airborne, are eager to identify a more specific number within that range. He said researchers would also like to detect mutations that make other H5N1 viruses airborne, as well as crucial characteristics that make the strain more transmissible in humans and other mammals.

He said his team worked with an Indonesian strain and Kawaoka's group worked with a Vietnamese strain, and that scientists are eager to learn more about mutations that might make strains from Egypt and China airborne.

He said the primary goal of the H5N1 transmission studies is to provide a fundamental understanding of the viruses, but he added the work could be useful for guiding countries in their virus eradication efforts and for evaluating what antiviral drugs and vaccines work best, especially against a virulent virus that replicates in the upper airways.

Voices of caution
Michael Osterholm, PhD, MPH, director of the University of Minnesota's Center for Infectious Disease Research and Policy, publisher of CIDRAP News, said discussion that took place during the year-long moratorium did not resolve a primary issue: how to safety share the information.

"The concerns I had 6 months ago I still have today," he said, alluding to a US advisory group's assertion that terror groups or others could use certain details of the H5N1 studies to make biological weapons.

The National Science Advisory Board for Biosecurity (NSABB), of which Osterholm is a member, in December 2011 had urged Science and Nature to omit key portions of Fouchier's and Kawaoka's studies, but in March 2012 reversed its recommendation. In the March decision, it unanimously voted that Kawaoka's full paper be published, but 6 of 18 members voted against the publication of certain details in Fouchier's study.

The journals eventually published full versions of both studies, Kawaoka's in a May issue of Nature and Fouchier's in a June issue of Science.

Osterholm said he believes the research work should be done. "I think Ron and Yoshi are two of the best researchers in the world to be doing this work, and I have faith in their practices," he said.

He said he still has concerns, however, about making the information available to groups that might not use the same level of care in handling transmissible H5N1 viruses, not only bioterror groups, but also vaccine companies that don't have impeccable safety measures or universities that don't have the most modern safety features and staff training.

He also says he doesn't believe scientists and health leaders have exhausted exploring all of the possible mechanisms for limiting key details of H5N1 transmission studies only with people who have a need to know. And while the emphasis of the debate seems to have shifted to biosecurity issues, accidental or intentional leaks are still a major concern for some settings. "All we have to do is be wrong once," Osterholm said.

Richard Ebright, PhD, molecular biologist at the Waksman Institute of Microbiology at Rutgers University who has an interest in biosecurity issues, told CIDRAP News that ending the moratorium is "premature and irresponsible." He added that the substantive issues and context haven't changed much over the past year.

"No independent risk-benefit assessment has been performed, and no independent decision has been reached that risks are outweighed by benefits. Not in the US. Not overseas," Ebright said in an e-mail, noting that efforts to implement the risk-benefit process are at the proposal state in the United States and in even earlier stages overseas.

He wrote that the WHO and NIH meetings that discussed the issues last year were dominated by handpicked panelists and featured scientists and funders who were involved in the work and had potential conflicts of interest. "Promises by the WHO and the NIH to hold a broader discussion, analogous to the Asilomar meeting that addressed the safety of recombinant DNA technology, have not been fulfilled," he wrote.

An editorial on the moratorium's lifting that appeared in Nature today acknowledged the lack of a formal risk-benefit assessment and alluded to the perception, justified or not, that the debate was dominated by researchers and funders and took place partially behind closed doors.

"The formal, quantitative risk assessment common in the nuclear power and other industries could have helped to nail down and quantify risks, and would have informed the debate better," the editorial stated. "One year on, an irreproachable, independent risk–benefit analysis of such research, perhaps convened by a body such as the World Health Organization (WHO), is still lacking."

However, the editorial noted that the moratorium period has yielded important fruit, such as greater scrutiny of public health benefit claims, better explanations of biosafety and biosecurity precautions, and more attention to dual-use research issues. The editorial lauded the WHO's guidelines on H5N1 transmission research and its recommendation that labs that can't identify and control the risks refrain from doing research on the viruses.

"The lifting of the moratorium by researchers must not be seen as closure of the debate. The potential risks of the work demand exceptional precautions in any future research," the editorial concluded.

See also:

Jan 23 Science letter

Jan 23 Nature letter

Jan 23 Nature editorial

Dec 26, 2012, CIDRAP News story "Experts differ on HHS select-agent proposal for H5N1"

Dec 18, 2012, CIDRAP News story "Experts at NIH meeting say H5N1 research moratorium may end soon"

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