H5N1 Flu Papers Published, but Moratorium Continues

The highly controversial report from Dutch flu researcher Dr. Ron Fouchier on creating a form of H5N1 avian influenza that’s airborne transmissible between mammals finally appeared this afternoon in Science magazine, after months of dickering over whether this paper would get published and what information it would include.

But, with much of the content of both Dr. Fouchier’s paper, as well as a report on a similar study by Dr. Yoshihiro Kawaoka that appeared last month in Nature, already fairly well known and widely discussed, perhaps the biggest news in today’s reports came in some of the related papers published by Science and in an update about the H5N1 research moratorium made during a press conference yesterday.

courtesy Plaskov, Wikimedia Commons

At the height of the mammalian-transmissible H5N1 debate last winter, Dr. Fouchier and Dr. Kawaoka and several other flu researchers declared a voluntary, temporary stop to any further research on the transmissibility or pathogenesis of H5N1. Speaking at a press conference on June 20 organized by Science magazine to discuss today’s package of H5N1 reports and analysis, Dr. Anthony Fauci, director of the National Institutes of Allergy and Infectious Diseases (which funded the transmissible H5N1 work), said, “The reason why you have not heard any announcement about the moratorium is that we are still struggling with the criteria for the next phases of experiments. We are working hard right now to get processes in place where we could have broad general criteria for the kinds of experiments that could be done.” A meeting is scheduled in July in New York that will bring together a worldwide group of influenza researchers and surveillance experts who will try to produce those criteria, Dr. Fauci said. The meeting “will discuss in detail the kinds of approaches we can have to try to expedite as quickly as possible the lifting of the moratorium.”

One of the new studies that accompany the Fouchier paper today is an analysis led by researchers at Cambridge University who used the findings on H5N1 mutations that contribute to mammalian transmissibility to develop a mathematical model to calculate the risk that such viruses could appear in nature. Their conclusion: Current best estimates indicate that the needed panel of mutations could evolve within a single mammalian host, making the possibility of a respiratory-drop transmissible strain of H5N1 virus occurring in nature “a potentially serious threat.” But a more quantifiable estimate of the risk—a specific number—is not yet possible, they said.

“We now know that we are living on a fault line, an active fault line,” when it comes to the potential for H5N1 to become mammalian transmissible in the real world, said Dr. Derek J. Smith, head of the Cambridge group, during yesterday’s press conference. “Now what we need to know is how likely it is.”

Another part of today’s H5N1 package dealt with steps that could be taken right now to speed up influenza vaccine production in response to a newly emerged pandemic strain, something that warrants its own blog post.

—Mitchel Zoler (on Twitter @mitchelzoler)

Controversy Over H5N1 Flu Continues

Just when it seemed like consensus existed on how to handle the hot potato of mammalian-transmissible H5N1 influenza, the public release on Friday afternoon of a letter sent April 12 from the respected influenza and public health researcher Dr. Michael Osterholm to a National Institutes of Health official collapsed the apparent consensus like a house of cards.

To recap: On March 29 and 30, the U.S. government’s National Science Advisory Board for Biosafety (NSABB), organized by the NIH’s Office of Science Policy, met to reconsider the NSABB’s original decision last December that said the paper written by Dr. Yoshihiro Kawaoka and another paper by Dr. Ron Fouchier on their respective efforts to produce and study H5N1 mutants transmissible by air from ferret to ferret should only be published without the methods sections, a way to prevent release of the details on how they developed these potentially dangerous mutant strains. The initial NSABB recommendation to allow publication of only the redacted papers failed to win support from a panel convened by the World Health Organization in February, creating a conflict between the NSABB (and hence the NIH) and the WHO. Claiming that new data first revealed to the WHO group led to the different outcome, Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases — the U.S. agency that sponsored the work of both Dr. Kawaoka and Dr. Fouchier — called on the NSABB to rethink its initial decision, which resulted in the NSABB reversing itself on March 30 and supporting full publication, in a unanimous vote for Dr. Kawaoka’s work, and in a 12-6 vote for Dr. Fouchier’s. So, by early April, the NSABB (and hence, pending official U.S. policy) and the WHO agreed that full H5N1 publication could proceed. Peace reigned across the land.

Dr. Michael Osterholm

Until 2 weeks later, when Dr. Osterholm an NSABB member, upset the tranquility by writing his bombshell letter to Dr. Amy Patterson, NIH’s associate director for Science Policy. In it, Dr. Osterholm took vigorous swipes at how the NIH set up the NSABB’s reconsideration session and detailed his grave concerns about public release of how the H5N1 work was done. Both “Science” and “Nature” received the letter on April 13, and according to a report in “Nature,” Dr. Osterholm said he was not the source for the leak.

“I believe the agenda and speakers for the March 29 and 30 NSABB meeting as determined by the Office of Biotechnology Activities [part of the NIH’s Office of Science Policy] staff and other U.S. government officials was designed to produce the outcome that occurred,” Dr. Osterholm charged in his letter. “It represented a very ‘one-sided’ picture of the risk-benefit of the dissemination of the information in these manuscripts. The agenda was not designed to promote a balanced reconsideration of the manuscripts.”

A major problem, he said, was that the “experts that addressed [the March NSABB session] have a real conflict of interest in that their laboratories are involved in this same type of work and the results of our deliberations directly affect them too.” The same problem occurred at the WHO meeting in February, he added.

Dr. Osterholm tempered his charge by saying he did not “suggest that there was a sinister motive by the U.S. government,” but still leveled a hefty blast, saying “I believe there was a bias toward finding a solution that was a lot less about robust science- and policy-based risk-benefit and more about how to get us out of this difficult situation.”

The upshot was that in the revised decision NSABB, U.S. policy makers, and researchers failed to “come to grips with the very difficult task of managing dual-use research of concern and the dissemination of potentially harmful information to those who might intentionally or unintentionally use that information in a harmful way.” His worry is — if not in this case — “will the Board ever find a bright line for redacting publication” of any future research that could potentially threaten public health?

Dr. Osterholm cited a major danger if details of this research became fully public: “A ferret-to-ferret experiment is expensive and technically demanding, and could only be done by a handful of labs in the world. Once the mutations are public, individuals … in many other labs could generate the mutants in a few weeks given several thousand dollars for gene synthesis,” using reverse genetics.

Finally, Dr. Osterholm questioned the public-health benefit from full release of the methods sections of the two H5N1 papers. “The most important aspect of the results in these two studies on surveillance and control has already been accomplished namely alerting the world to the possibility that H5N1 influenza virus surely can become a mammalian-transmitted virus and poses real pandemic potential.” Publication of more details from the research will not add to that alert, nor would it immediately help in the development or production of countermeasures against a potential H5N1 pandemic, he said.

Despite his concerns over full disclosure of the methods, Dr. Osterholm affirmed his overall support for this H5N1 research in a comment to “Nature” on Friday.  “I have been and continue to be a supporter of this kind of research,” he told the journal.

—Mitchel Zoler (on Twitter @mitchelzoler)