Typically, Perez said, this is done by placing the virus in ferret noses, waiting a few days, swabbing out some mucus, infecting another ferret with it, and repeating the process over and over. Throughout the process, infected and uninfected ferrets would be placed in adjacent cages to see whether the virus could pass from one animal to the other without them touching.
The Dutch team completed its experiment and made an alarming discovery.
According to published news reports from Fouchier's presentation at a September conference in Malta, just five tweaks in two genes, followed by just 10 passages of the virus between ferrets, created a pathogen that could travel through the air from animal to animal.
The virus remained lethal.
"We were surprised by how quickly it was able to become airborne," Fouchier said. "We came up with a bunch of experiments, and it happened with the simplest one."
Fouchier said his work should prod countries where the virus is widespread, such as Indonesia, Vietnam and Egypt, to work more aggressively to prevent a pandemic.
"This research brings H5N1 viruses to the very top of the ones we should be concerned about," said Richard Webby, a virologist who studies flu pandemics at St. Jude Children's Research Hospital in Memphis, Tenn.
Further study of the mutations implicated in Fouchier's work — and new research at the University of Wisconsin-Madison that was also reviewed by the National Science Advisory Board for Biosecurity — could help scientists improve vaccines and antiviral drugs, Perez said. Only by understanding how a dangerous version of H5N1 is likely to look genetically can scientists develop effective vaccines before it's too late.
The information would also help hone monitoring in the field, Webby said. Say, for example, samples of H5N1 collected in Egypt were found to share four of the five genetic changes that exist in Fouchier's killer strain.
"Knowing that information tells us we're only one step away" from a pandemic, Webby said. "That would increase surveillance and eradication programs."
But just because this deadly combination of mutations is in the cross hairs doesn't mean different combinations couldn't arise in the wild and be just as lethal, scientists said.
"Flu always does things we don't expect," Webby said.
Northern Arizona University geneticist Paul S. Keim, acting chairman of the biosecurity board, said that the debate over what to do about so-called dual-use biological research — work that can be applied to good or evil ends — had been simmering at least since the 2001 anthrax attacks, when spores believed to be taken from a laboratory were sent through the mail, killing five people and sickening 17.
Since its 2004 creation, the biosecurity board has been asked by the Department of Health and Human Services to review about half a dozen papers concerning potentially dangerous research results, Keim said. These included studies of smallpox and the 1918 Spanish flu, estimated to have killed at least 50 million people.
This is the first time the board has ever asked researchers to redact details.
Keim called the episode "a watershed moment" for the U.S. government that could change the way such dual-use work is conducted.
The board, which makes recommendations but doesn't set policy, will spend the next few weeks developing guidelines for scientists and governments around the world, he said. The board might suggest a short-term moratorium on publishing or presenting further research on transmission of H5N1 flu while it ponders not only whether sensitive research is published but also what should be studied to begin with, and how.
"In the future, this area will be examined from start to finish," Keim said.
The immediate issue is what to do with the new H5N1 papers.
Editors at the journals Science and Nature, who had agreed to publish the Dutch and U.S. research, respectively, said last week that they were awaiting word that the U.S. government had devised a way to share the findings with scientists who have legitimate reasons to see them while keeping the data from becoming a how-to guide for would-be bioterrorists. The process could take months.
Fouchier said he was cooperating, but he thought the strategy was impractical. When he and his colleagues made a list of the people they thought should see the data, they came up with more than 100 international organizations — close to 1,000 individuals.
"As soon as you share information with more than 10 people, it's no longer confidential," he said. "Our opinion is, and has been, that it would be best to publish the research, in a responsible way."
Richard Ebright, a molecular biologist at Rutgers University in Piscataway, N.J., who is a critic of the way the scientific community handles dual-use work, said the H5N1 debate highlighted a basic flaw in the system. Experiments like these should be more formally assessed for their risks and benefits before they're ever embarked on, he said.
"That's not done today, and that's what brought us to this situation," he said.
He said that at this late stage in the game, the H5N1 research should be published in its entirety because plans to limit access will be expensive, unwieldy and unworkable.
Besides, he said, labs could probably reproduce Fouchier's experiment already based on information that has been circulating for months.