Scientists Brace for Media Storm Around Controversial Flu Studies





The other study—also on H5N1, and with comparable results—was done by a team led by virologist Yoshihiro Kawaoka at the University of Wisconsin, Madison, and the University of Tokyo, several scientists told ScienceInsider. (Kawaoka did not respond to interview requests.) Both studies have been submitted for publication, and both are currently under review by the U.S. National Science Advisory Board for Biosecurity (NSABB), which on a few previous occasions has been asked by scientists or journals to review papers that caused worries.




The research by the Kawaoka and Fouchier teams set out to answer a question that has long puzzled scientists: Does H5N1, which rarely causes human disease, have the potential to trigger a pandemic? The virus has decimated poultry flocks on three continents but has caused fewer than 600 known cases of flu in humans since it emerged in Asia in 1997, although those rare human cases are often fatal. Because the virus spreads very inefficiently between humans it has been unable to set off a chain reaction and circle the globe.

Some scientists think the virus is probably unable to trigger a pandemic, because adapting to a human host would likely make it unable to reproduce. Some also believe the virus would need to reshuffle its genes with a human strain, a process called reassortment, that some believe is most likely to occur in pigs, which host both human and avian strains. Based on past experience, some scientists have also argued that flu pandemics can only be caused by H1, H2, and H3 viruses, which have been replaced by each other in the human population every so many decades—but not by H5.

Fouchier says his study shows all of that to be wrong.

Although he declined to discuss details of the research because the paper is still under review, Fouchier confirmed the details given in news stories in New Scientist and Scientific American about a September meeting in Malta where he first presented the study. Those stories describe how Fouchier initially tried to make the virus more transmissible by making specific changes to its genome, using a process called reverse genetics; when that failed, he passed the virus from one ferret to another multiple times, a low-tech and time-honored method of making a pathogen adapt to a new host.


Ferrets aren't humans, but in studies to date, any influenza strain that has been able to pass among ferrets has also been transmissible among humans, and vice versa, says Fouchier: "That could be different this time, but I wouldn't bet any money on it."

The specter of an H5N1 pandemic keeps flu scientists up at night because of the virus's power to kill. Of the known cases so far, more than half were fatal. The real case-fatality rate is probably lower because an unknown number of milder cases are never diagnosed and reported, but scientists agree that the virus is vicious. Based on Fouchier's talk in Malta, New Scientist reported that the strain created by the Rotterdam team is just as lethal to ferrets as the original one.



Fouchier says he consulted widely within the Netherlands before submitting his manuscript for publication. The U.S. National Institutes of Health (NIH), which funded the work, has agreed to the publication, says Fouchier, including officials at the National Institute of Allergy and Infectious Diseases. (NIH declined to answer questions for this story.) Now, Fouchier is eagerly waiting for NSABB's judgment.


But some scientists say the board's debate comes far too late, because the studies have been done and the papers are written. "This is a good example of the need for a robust and independent system of PRIOR review and approval of potentially dangerous experiments," retired arms control researcher Mark Wheelis of the University of California, Davis, wrote to ScienceInsider in an e-mail. "Blocking publication may provide some small increment of safety, but it will be very modest compared to the benefits of not doing the work in the first place."

Scientists have long discussed whether to have mandatory reviews of dual-use studies before they begin, and given the global risks, some have even argued for some international risk assessment system for pandemic viruses. For instance, a proposal by four researchers from the Center for International and Security Studies at Maryland would have classified Fouchier's work as an "activity of extreme concern" that would have required international pre-approval.

But NSABB advised against such mandatory systems in 2007, and most countries don't have formal mechanisms in place to review studies before they start. (In the United States, it's "recommended" that researchers ask an institutional review board for advice if they think a study raises concerns.) Fouchier's study was greenlighted in advance by the Dutch Commission on Genetic Modification (COGEM), but that only means the panel is satisfied with safety procedures at Fouchier's lab, explains chair Bastiaan Zoeteman; it's not COGEM's job to decide whether a study is desirable. NIH didn't give the funding proposal a special review either, says Fouchier.

"The creation of a pandemic virus has been the classical example of dual-use research of concern the past decade," says Ebright. "It's remarkable that the NSABB is discussing it in 2011."

Keim agrees about the need for reviews up front. "The process of identifying dual use of concern is something that should start at the very first glimmer of an experiment," he says. "You shouldn't wait until you have submitted a paper before you decide it's dangerous. Scientists and institutions and funding agencies should be looking at this. The journals and the journals' reviewers should be the last resort."

NSABB does not have the power to prevent the publication of papers, but it could ask journals not to publish. Even Ebright, however, says he's against efforts to ban the publication of the studies now that they have been done. "You cannot post hoc suppress work that was done and completed in a nonclassified context," he says. "The scientific community would not stand for that."