Research

New Paper Points at Ways to Stop—Not Start—a Bird-Flu Pandemic

Levien Willemse

Ron Fouchier, virologist at Erasmus Medical Center, in Rotterdam, is lead author of a controversial paper on bird flu that has finally been published.
June 21, 2012

In the end, the paper once deemed too dangerous to publish turned out to be about saving lives.

On Thursday, Science magazine published research showing that a few mutations in the bird-flu virus, H5N1, could turn it into a disease easily transmitted, by air, among mammals. Normally, the virus doesn't spread easily among people, but when it does, the death rate is high. So when Ron Fouchier, a virologist at Erasmus Medical Center in the Netherlands and the paper's lead author, created this new strain, it ignited a storm of controversy as scientists and policy makers debated whether he had identified warning signs of a potential pandemic—or given terrorists and sloppy scientists a recipe for unleashing a plague.

In December, a federal advisory panel, backed by the National Institutes of Health, censored the paper, saying that scientific data had to be removed before it was published.

The tone was quite different on Thursday. "I believe the benefits are greater than the risk," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, a division of the NIH. One major advantage: The paper shows mutations to watch for in the wild, before they become the seeds of a pandemic flu.

The paper, along with a similar study published in May in the journal Nature will also push forward scientific understanding of how a virus becomes more infectious and moves from one kind of animal to another, Dr. Fauci said. Because flu is a deadly disease worldwide, and it rapidly changes its form, foiling vaccines, these things "far outweigh the risk of nefarious use of this information," he noted.

The author of the Nature paper, the virologist Yoshihiro Kawaoka of the University of Wisconsin at Madison, whose work was also held back in December, said that the scientific content of both papers was unchanged from their original. "We provided more information on the benefits of this work and the biosafety and biosecurity involved," he said. During the months of delay and debate, "it became clear that most people don't understand the precautions necessary to do research like this, so adding that section to the papers was needed." (The panel that originally pushed for censorship, the National Science Advisory Board for Biosecurity, reversed its decision in March, after the scientists added more details about their cautious laboratory approach.)

Indeed, scientists who initially argued the work should not have been done, like D.A. Henderson, the infectious-disease specialist who led the worldwide effort to eradicate smallpox and is now a distinguished scholar at the Center for Biosecurity of the University of Pittsburgh Medical Center, now feel the risk has been somewhat mitigated because of heightened awareness. The danger, he said, was not so much a terrorist using mutant flu as a bioweapon as it was a careless scientist trying to replicate the work and accidentally releasing a deadly flu against which there is no antidote. But the papers make it clear the work was done in high-security labs and should only be undertaken in those conditions.

The scientific value of the papers is that they show not just one but two ways in which H5N1 can become a threat to mammals, including people. "We proved that H5N1 is not just a problem for the poultry industry," said Mr. Fouchier.

His work showed that as few as five mutations within the virus could transform it. Some of those changes were in a gene for hemagglutinin, which helps the virus stick to cells in particular animals. Two, however, were previously unknown, and appeared to be key to letting the virus infect the upper respiratory tract, which made it more easily transmissible.

Mr. Kawaoka's research, on the other hand, showed that H5N1 could acquire genes from outside, specifically another flu virus called H1N1, and use them to stick better to mammal cells and become more stable.

In a hopeful sign, neither new virus killed the animals they were tested on, ferrets, and both strains were weakened by an antiviral drug, Tamiflu.

Derek J. Smith, a professor of infectious disease informatics at the University of Cambridge, has modeled the evolution of these mutations and said they could occur together within a single species, like chickens. But he was not able to say how likely this was. The situation is a little like trying to predict an earthquake or a tsunami well in advance, he said. "We now know that we're living on a fault line. What we have discovered in this working collaboration with Fouchier and Kawaoka is that it's an active fault line. It really could do something."

So that researchers too can do something without running into a seven-month delay, the federal government in March announced a new policy on "dual use research of concern," beneficial work that could have a dark side. The policy was outlined in general terms, calling for agencies that finance such research at universities to review it more often, and for universities themselves to clarify the precautions taken. But "we are struggling a bit with the criteria," said Dr. Fauci, particularly when it comes to local oversight by institutions, adding that the goal is to avoid "the same situation that the Fouchier paper ran into the first time around." A draft version of the more-detailed policy could be published in the Federal Register in July, he hoped, and opened for public comment.