Experts debate aspects of H5N1 transmission studies

Jan 23, 2012 (CIDRAP News) – More experts weighed in recently on various aspects of yet-unpublished H5N1 avian influenza transmissibility studies that have raised concerns about the risk of an intentional or accidental release of the mutant pathogens, as well as worries about scientific censorship.

The views, which include those from a Dutch research group that conducted one of the studies and a member of a US government panel that advised publishing only redacted versions of them, appeared in a group of commentaries posted on the Science Web site Jan 19.

The H5N1 study by Dr Ron Fouchier's group from Erasmus University in the Netherlands is slated for publication in Science. The second of the two studies, by Dr Yoshihiro Kawaoka and colleagues from the University of Wisconsin at Madison, is expected to appear in a future issue of Nature. Earlier last week, Nature published a similar collection of commentaries on the issues surrounding the studies.

The commentary by Fouchier and colleagues contained some fresh details about the background of the study, along with their view that the full version of their report should be published.

They wrote that their research goal is to explore whether the H5N1 virus can gain the ability to spread by aerosol transmission and if such a strain would retain its virulence, which has been a key question in assessing the world's pandemic risk and would play a role in preparedness planning.

The lab's work on aerosol H5N1 transmission has been done openly, and the decisions to do the studies were guided by local, national, and international input, the group wrote. They also detailed the steps that led to a research contract from the US Department of Health and Human Services (HHS).

In a description of the safety level and conditions at the lab, they wrote that the facility is regularly inspected by the US Centers for Disease Control and Prevention using US "select agent" rules for overseas labs. The most recent inspection in February 2011 found no safety or security gaps, they said.

Regarding a recommendation from the National Science Advisory Board for Biosecurity (NSABB) that the published study be redacted to exclude methodologic details and mutation data and that a system be devised to share sensitive details with those who need to know, Fouchier's team asserted that decisions about who should see the full details should be broad-based. They said decision making should include health officials in countries where H5N1 infections occur in humans and animals, as well as global health labs, companies, and research groups that produce countermeasures.

The NSABB is HHS's independent advisory group on dual-use research.

Fouchier's group also warned that H5N1 research labs that do similar work also need to know the full details, because they may unknowingly develop high-risk variants. Based on a literature review, they argued that labs working on H5N1 viruses may need only one to three mutations before they gain the ability to transmit by aerosols.

Though the group disagrees with the NSABB recommendations, they said they respect the advice and hope to find a solution for sharing key information with those who need to know while preventing possible misuse of the data. "However, we cannot rule out the possibility that new scientific research, outbreak events, political sensitivities, or other circumstances may call for deviation from this route," they wrote.

In a separate commentary, Dr Daniel Perez, a virologist who studies flu in animals at the University of Maryland, argued against stopping or limiting H5N1 transmission research. He wrote that identifying the molecular attributes that allow flu viruses to spread by aerosol transmission is a key to predicting or preventing the emergence of a pandemic strain.

Researchers have taken only a few steps in understanding flu transmission, he wrote. "In this regard, the independent work by Fouchier's and Kawaoka's groups showing that H5N1 can be transmitted by respiratory droplets in the ferret model is of great importance."

"If there ever was a sense of complacency about H5N1 viruses," he added, "these studies are a wake up call."

He said he respects the NSABB's recommendation but believes it is impossible to block access to the methodology, because the two groups and other researchers have already published similar studies.

Restricting access to key information could hamper the development of vaccines and antivirals against the virus, Perez wrote. He told CIDRAP News that it's not yet known if the amino acid changes in the mutated H5N1 viruses would have an impact on the antigenic make-up of the virus. He added that researchers will need to assess those changes to determine if existing H5N1 stocks are a good match for the virus or if a new seed stock needs to be developed.

He urged health leaders not to block H5N1 research over fears of possible misuse, pointing out that bold measures led to the eventual eradication of smallpox.

In a commentary arguing against the release of the study details, Dr Michael T. Osterholm and Dr Donald A. Henderson wrote that experts should keep in mind that with a human case fatality rate that ranges from 30% to 80%, circulating H5N1 strains are among the most virulent known human pathogens.

Osterholm is a member of the NSABB and director of the University of Minnesota's Center for Infectious Disease Research and Policy, which publishes CIDRAP News. Henderson is with the Center for Biosecurity at the University of Pittsburgh Medical Center and led the global effort to eradicate smallpox in the 1960s and 1970s.

The two authors questioned how useful the full details would be for surveillance purposes, given the difficulties H5N1-endemic nations have with detecting and responding to poultry outbreaks. Even if the countries had good lab capacity and could process samples quickly, the countries often lack the commitment for aggressively addressing H5N1 issues, they wrote.

The 2009 H1N1 pandemic is a recent example of how difficult it is to it is to quickly identify and contain an emerging pandemic virus, Osterholm and Henderson said.

Osterholm told CIDRAP News that trying to use mutation data to improve surveillance "is like putting a different colored cover on a smoke alarm that has no batteries or electricity."

Osterholm and Henderson also asserted that novel antigens that are potentially altered by mutational changes in one of the studies wouldn't drive H5N1 vaccine research using current methods that rely on hemagglutinin and neuraminidase antigens. Though H5N1 candidate vaccines against the viruses should be developed and tested, the process wouldn't require sharing mutation data outside a small group of researchers, they added.

A better option for protecting the world against the next pandemic flu strain would be to develop, license, and produce next-generation flu vaccines that are effective against a range of strains and are more readily available to the world in the early weeks of an outbreak, they wrote.

In the view of Osterholm and Henderson, since sharing the full details of the study won't materially increase preparedness against an H5N1 pandemic, efforts should instead focus on making sure the information doesn't fall into the wrong hands and that an accidental lab release doesn't occur.

If a transmissible human-made H5N1 virus sparks a severe pandemic, "the world will hold life sciences accountable for what it did or did not do to minimize that risk," they write.

Osterholm told CIDRAP News that those concerned about the bioterror or accidental release risks aren't belittling H5N1 researchers or saying that much of the work isn't needed. Rather, he said, experts should think about what kind of research is truly needed as they assess the potential risks.

Perez told CIDRAP News that he agreed that experts should be thinking about ways to improve vaccines, but he said the world is not even close to a universal vaccine, saying, "What we have to deal with now is the current technology."

He said rather than worrying about what some labs might do with the information in the two H5N1 transmission studies, experts should devote more efforts to figuring out how to get rid of H5N1 in poultry. Perez also said global health officials should put more pressure on countries to control H5N1 in poultry.

In a fourth commentary in the series, two legal experts discussed the limits of government regulation in science. They noted that although the government has tried to block scientific publication twice before, the H5N1 case is the first request to withhold information after an HHS review process.

The authors are John D. Kraemer and Lawrence O. Gostin, both with the O'Neill Institute for National and Global Health Law at Georgetown University in Washington, DC.

They wrote that the HHS advisory group's request does not violate the First Amendment, because it is nonbinding. In some situations, the government can block scientific communications, such as when the information has been properly classified under federal law.

In exploring whether information deleted from the H5N1 reports could be obtained through a Freedom of Information Act (FOIA) request, Kraemer and Gostin said FOIA rules apply only to agency records, and a key question would be whether data acquired under a grant constitutes an agency record.

They said that in 1980 the Supreme Court ruled that research data produced under an NIH grant was not an agency record, because it was retained by the grantee.

See also:

Fouchier RA, Herfst S, Osterhaus DME. Restricted data on influenza H5N1 virus transmission. (Commentary) Science 2012 (published online Jan 19) [Full text]

Perez DR. H5N1 debates: hung up on the wrong question. (Commentary) Science 2012 (published online Jan 19) [Full text]

Osterholm MT, Henderson DA. Life sciences at a crossroads: respiratory transmissible H5N1. (Commentary) Science 2012 (published online Jan 19) [Full text]

Kraemer JD, Gostin L. The limits of government regulation of science. (Commentary) Science 2012 (published online Jan 19) [Full text]

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