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Free to Speak, Kawaoka Reveals Flu Details While Fouchier Stays Mum

3 April 2012 5:53 pm
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LONDON—Influenza virologist Yoshihiro Kawaoka finally told a captive audience here the key details of the study that helped trigger an exhaustive review by a U.S. biosecurity panel as well as one of the most intense bioethical debates in years. Speaking at a 2-day meeting at the Royal Society, Kawaoka revealed the four mutations that made a reassortant flu virus more transmissible among ferrets through tiny droplets—a finding that had triggered worries that it could cause an influenza pandemic.

By contrast, Ron Fouchier of the Erasmus Medical Center in Rotterdam, the Netherlands—the main author of the other flu study reviewed by the U.S. National Science Advisory Board for Biosecurity (NSABB)—was forced to stick to a skeletal talk that contained few details about his own work, as he has been doing since he first presented the study at a meeting in Malta in September. The Dutch government is currently holding up the release of Fouchier's study because it believes it might violate export control rules.

Fouchier doesn't believe the authorities have a case and says he would be "happy to go to court" over the issue, if it weren't for the fact that breaking his silence would also put co-authors and officials at Erasmus MC in legal jeopardy.

The presentations at the meeting, which attracted about 150 attendees, came in the wake of a new review by the NSABB. On Friday, the board voted to recommend full publication of both studies, and Nature has said it will publish Kawaoka's paper as soon as possible. Kawaoka says a lawyer for his employer, the University of Wisconsin, Madison, gave the green light for his presentation here after the NSABB recommendation, but stresses that even without it, he does not believe his talk would have violated any laws or regulations.

Both studies made a flu virus more transmissible among ferrets, but there were important differences. Fouchier's group worked with the H5N1 avian influenza strain; Kawaoka took the gene for hemagglutinin (HA) from that virus—which he says was his key interest—and placed it in the H1N1 virus that caused the 2009 pandemic; he then set out to find out which changes make the resulting virus more easily transmissible among ferrets.

A series of experiments eventually showed that four mutations produced a virus that transmitted well among the animals, he said. Two of the mutations are in a region well known to play a role in host specificity; they are believed to help HA latch onto mammalian receptors. Another mutation increased HA's stability, which Kawaoka says could be important when the virus replicates in a mammalian host. The role of the fourth mutation is less clear.

In a transmission study of the virus with all four mutations, six out of six ferrets became infected when housed in a cage close to an animal that already carried the virus, allowing the virus to transmit through sneezing and coughing. Fouchier's results partly match his own, Kawaoka said. "I wish Ron could report everything," he said. "We found striking similarities."

Kawaoka also mounted a vigorous defense of the studies' importance, pointing out that they formed part of an established research program deemed important in reports by the U.S. National Institutes of Health and the World Health Organization, and that similar transmission studies had been carried out and published for years. He spoke at length about the safety and security procedures at his lab.

Meanwhile, the reasons for the change of heart at NSABB—which one attendee described as having "multiple personality disorder"—came under scrutiny as well. NSABB acting chair Paul Keim explained that the group was swayed by new and confidential information about both the risks and the potential benefits of the studies and by the fact that the U.S. government is putting in place a new policy that will provide a much more comprehensive review of so-called dual use research of concern. It had also concluded that redacting critical information and making it available only to people with a legitimate interest in seeing it was, at least in the short run, unworkable.

But another key reason, Keim said, was that Fouchier has revised and expanded his manuscript, which now makes clear that the newly created virus isn't deadly when transmitted from one ferret to another through sneezing and coughing. Based on Fouchier's first manuscript and interviews he gave in the press, the board was under the impression that the virus was lethal under those conditions, too, says Robert Webster, an influenza virologist at St. Jude Children's Research Hospital in Memphis, Tennessee, who advised NSABB during both its first and second review. "That scared the jesus out of everyone," he says.

Once the group had read the revised paper, it became clear that it was all a "giant misunderstanding," Webster says. At a press conference yesterday, Fouchier said the information about virulence was in the original paper, although perhaps not presented as clearly as it could have been because the paper was short.

For an in-depth look at how NSABB came to its new decision, read Friday's print edition of Science.

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