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Infectious Disease

Bird flu paper that raised bioterrorism fears published

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The journal Nature has published the first of two controversial papers about laboratory-enhanced versions of the deadly bird flu virus that initially sparked fears among U.S. biosecurity experts that it could be used as a recipe for a bioterrorism weapon.

The publication of the paper by Yoshihiro Kawaoka of the University of Wisconsin, Madison, on Wednesday follows months of acrimonious debate that pitted the need for science to be free of censorship against the obligation to protect the public from a potentially devastating flu pandemic.

Bird flu is lethal in people and spreads among those who are in close contact with infected birds, but so far, the virus known as H5N1 has not had the ability to pass easily among humans through sneezing and coughing, and some scientists had begun to doubt that that was possible.

The studies by Kawaoka and Dr. Ron Fouchier of Erasmus Medical College in the Netherlands changed that view by proving that with a few genetic mutations, the virus could pass easily among ferrets, which are used as a close approximation of how a virus might behave in people.

"There are people who say that bird flu has been around for 16, 17 years and never attained human transmissibility and never will," said Malik Peiris, virology professor at the University of Hong Kong.

"What this paper shows is that it certainly can. That is an important public health message, we have to take H5N1 seriously. It doesn't mean it will become a pandemic, but it can," said Peiris, who wrote a commentary accompanying Kawaoka's paper in Nature.

The impending publication of the two papers last December prompted the National Science Advisory Board for Biosecurity to recommend that sensitive information be redacted, a first for the group which was formed after a series of anthrax attacks in the United States in 2001.

The group advises the Department of Health and Human Services and other agencies about "dual use" research that could serve public health but also be a potential bioterrorism threat.

Weighing the risks

The National Institutes of Health, which funded some of the research, agreed with the panel's assessment and made non-binding recommendations to Nature and Science, the journal that planned to publish Fouchier's study, to withhold key elements of the work.

But after a series of meetings involving flu experts and officials at the World Health Organization and the National Institutes of Health in the United States, the NSABB reversed its decision.

The group voted unanimously to support publication of the paper by Kawaoka, considered the least controversial of the two.

And it voted 12-6 in favor of publishing a study from Erasmus Medical Center in the Netherlands, but did not explain the concerns among some panel members about that research. Science has not given a specific date for its publication.

Kawaoka said in an email he believed that in face-to-face meetings with members of the NSABB in March, he was able to explain in greater detail the full implications of his experiments and win the panel's support.

Kawaoka's team developed a hybrid virus by taking the hemagglutinin gene from the H5N1 virus and combining it with the pandemic strain of the 2009 H1N1 swine flu virus.

Then, by adding four other gene mutations, plus some spontaneous changes that occurred in the ferrets, the virus became transmissible among ferrets - the best model scientists have for predicting whether a flu virus can be transmitted among humans, Peiris said.

"But it doesn't necessarily mean that just because this virus transmitted in ferrets, it will 100 percent transmit in humans, but it's as close as we can get. It lost a lot of its virulence in ferrets, maybe because of the H1N1 backbone," Peiris said.

Kawaoka said his manuscript has been updated to provide more information about the benefits of these findings, particularly the risk posed by currently circulating viruses that already have one of these mutations.

"In addition, we provided more details about the biosafety and biosecurity measures in place to conduct these experiments," Kawaoka said.

Arturo Casadevall, a microbiologist from Albert Einstein College of Medicine in New York and a member of NSABB, said from his own perspective, he still believes there is risk in publishing information on how to increase the transmissibility of the bird flu virus, but publishing the study also gives scientists around the world a better idea of what to watch for in viruses already circulating.

Knowing that bird flu has the potential to jump more easily from human to human may now encourage governments to do a better job of tracking this potential threat.

"We feel the risk is still there, but the benefits now outweigh the risks," he said.