After a marathon debate over a pair of controversial studies that show how the avian H5N1 influenza virus could become transmissible in mammals, and initially sparked fears among U.S. biosecurity experts that it could be used as a recipe for a bioterrorism weapon, one of the studies was finally and fully published online Wednesday in the journal Nature.

The study, conducted by an international team of researchers led by Yoshihiro Kawaoka, a University of Wisconsin-Madison flu researcher, shows that some viruses now circulating in nature require just four mutations to the hemagglutinin protein, which sits on the virus surface and enables it to bind to host cells, to become an even greater threat to human health.

A subset of the mutations identified by the Wisconsin group has, in fact, already been detected in some viruses circulating in poultry flocks in Egypt and parts of Southeast Asia, underscoring the urgency of science-based surveillance, Kawaoka says.

In the Nature report, Kawaoka's group describes a laboratory- modified bird flu/human flu hybrid virus that can become transmissible in an animal model for human infection with just a handful of mutations. Because flu viruses in nature are constantly changing as they circulate and easily swap genes with other flu viruses, the possibility of circulating H5N1 viruses hitting the right combination of mutations and becoming a much bigger threat to human health is greater than many experts believed, avers Kawaoka.

Since late 2003, the H5N1 viruses have infected at least 600 humans, mostly in Asia, and killed more than half of the people infected. But the virus, which can be acquired through close contact with domestic fowl, does not easily transmit from human-to- human, a phenomenon that led some scientists to believe H5N1 posed little threat as a potential agent for a global flu pandemic. However, the studies by Kawaoka and Dr. Ron Fouchier of Erasmus Medical College in the Netherlands changed that view.

The impending publication of the two papers by Kawaoka and Fouchier last December prompted the U.S. National Science Advisory Board for Biosecurity (NSABB) to recommend that sensitive information be redacted. The National Institutes of Health, which funded some of the research, agreed with the panel's assessment and made non-binding recommendations to Nature and Science, the journal that planned to publish Fouchier's study, to withhold key elements of their work. But after a series of meetings involving flu experts and officials at the World Health Organization and the U.S. National Institutes of Health, the NSABB reversed its decision.

Science has not given a specific date for its publication.