Some biosecurity experts are concerned the research could be used as a blueprint by nefarious forces and are arguing against publication of the work.
But others, especially influenza scientists, are countering that the flu world needs to know the possible paths the H5N1 virus could take to become one that can spread easily among people so laboratories can be on the lookout for those changes in nature.
``There's been a general interest in understanding what the potential for human transmissibility is from H5N1 and from other influenza viruses. There certainly is an abiding interest in that question _ a policy interest, a public interest, so that is true,'' says Dr. Thomas Inglesby, director of the Center for Biosecurity of the University of Pittsburgh Medical Center in Baltimore, Md.
``But I think that has to be measured against the downside of actually demonstrating the transmissibility in ferrets as a surrogate for people, at one level. And then beyond that an even higher downside of describing in detail the methods by which this experiment could be done again.''
A panel of experts that advises the U.S. government on issues where science and terrorism have the potential to intersect is studying the research. The National Security Advisory Board on Biosecurity deals with issues of so-called dual use _ science that is done for valid reasons, but which would be used for evil ends.
The National Security Advisory Board on Biosecurity will not comment on the issue.
The body does not have the power to bar publication, but it is unclear whether a scientific journal would feel comfortable publishing an article if the group says it should not be placed in the public domain.
It's also not clear whether the funders of the research _ in this case, the U.S. National Institutes of Health _ would permit publication if the government's biosecurity advisers objected to publication of an article.
The controversy relates to several papers, two of which have recently been published and another which is in the publication pipeline.
That latter paper is the one garnering the most concern.
The senior author, virologist Ron Fouchier of Erasmus Medical Centre in Rotterdam, the Netherlands, won't talk about the work other than to confirm it is under review by the National Security Advisory Board on Biosecurity.
But Fouchier electrified the flu world in September when he gave an outline of the work at a major influenza conference in Malta.
He told the gathering that in trying to find out whether H5N1 could acquire the ability to spread easily among people, he came up with a virus that spread among ferrets as easily as seasonal flu viruses, according to a report on the meeting in Scientific American.
Ferrets are considered the best animal model for human infection with influenza. It is feared that a virus that could spread easily among the animals would spread easily among people as well.
H5N1 currently does not transmit easily to people or among people. To date there have been 570 confirmed cases of H5N1 infection in 15 countries and 335 of those people have died.
Inglesby says he believes science needs to be conducted and published, but in some cases, some science is too dangerous to be put into the public domain. He says this study may be one such case.
``I think that that principle is one of the underpinnings of science, but it's colliding in this case with a higher principle that science that produces either deliberately or inadvertently results which could lead to widespread dangers _ directly lead to widespread dangers _ should not be immediately reproduced for the world to see,'' he says.
Flu scientists, on the other hand, may feel like they are caught in a Catch-22 situation. For years they've faced demands from governments anxious to know whether H5N1 could become a human flu virus and what it would take for that to happen.
They've done a series of studies in labs specially designed to protect against inadvertent release of pathogens, under strict biosafety conditions, with clearances from institutional ethics committees or biosecurity committees.
Two recently published studies, one by scientists from the U.S. Centers for Disease Control and another by scientists at St. Jude's Children's Hospital in Memphis, Tenn., both involved engineering viruses with some genes from H5N1 viruses.
Both studies were published without being referred to the biosecurity advisory board.
Nancy Cox, head of the CDC's influenza division, says CDC follows strict rules when deciding whether a study is safe to do and whether results should be published. The agency uses a risks-benefits matrix designed by the biosecurity advisory board, she says, to guide those discussions.
And virologist Lynn Enquist, editor-in-chief of the Journal of Virology, which published the St. Jude's study, says that paper didn't ring the types of alarm bells that would prompt a referral to the advisory board. It involved putting a key gene from the H5N1 virus into the H1N1 virus that caused the 2009 pandemic.
Enquist, who is chair of molecular biology at Princeton University, sits on the National Science Advisory Board for Biosecurity.
He can't talk about the group's ongoing discussions. But speaking in general terms, he says decisions in this area are tough calls.
``On the one hand you can say `If you don't do this work we'll never know what's going on' and on the other hand you can say `If somebody gets a hold of this, it could be a problem,' `` he says.
``I find it really, really hard to think about telling people not to do science. My job as a scientist is to publish the very best I can under the safest and most legal conditions that are possible and get stuff out there. But there are other people who think we have to be really careful about what we do. And we have to think about that too.''
In Fouchier's case, his institution had to approve the work, and then had to apply to the Dutch government for clearance. His work was funded by the U.S. National Institutes of Health, and his laboratory had to pass inspection by the CDC.
Flu virologist Adolfo Garcia-Sastre knows about working with dangerous flu viruses. He was part of the team that reconstructed the virus that caused the 1918 Spanish flu, the worst pandemic in known history.
Garcia-Sastre was not involved in Fouchier's work and doesn't want to talk about a study he has not yet read. But he says science needs to know how to spot dangerous changes in flu viruses in nature.
``I think it's important to know all the ways how a virus can become transmissible to understand how close viruses are to (becoming) transmissible in nature,'' says Garcia-Sastre, who works at Mount Sinai Hospital in New York City.
``If not, we cannot be prepared.''
Cox agrees. ``We would like to know what are the danger signals.''
``It's a very delicate issue as to whether or not you might be potentially tempting someone with mal intent to create a virus that could be easily transmitted,'' she admits.
''But I have to say that even if you have very efficient transmission in ferrets you might not have efficient transmission in humans. It's an indicator, but it's not an absolute predictor.``
Inglesby is unconvinced that those benefits outweigh the risks of this type of work.
``If the goal of the experiment is to create a virus for which there currently is no vaccine or treatment, that if it escapes from the lab by accident could start a pandemic , if that literally is one of the outcomes of the experiment, I think the benefits of that would have to be extraordinary to justify that.''
Note to readers: This is a corrected story. An earlier version on Nov. 19 gave wrong information about funding for Fouchier's work.Suggest a correction