In birds the virus both spreads and kills rapidly. Chickens can die within hours of exposure. To prevent its further spread, tens of millions of birds have been destroyed in Asia.
Scientists had long believed it was impossible for a bird-flu virus to invade and grow in human cells. But then in 1997 a cousin of the H5N1 virus killed 6 of 18 people infected in Hong Kong.
Still, it is hard for people to catch bird flu. Of the 130 people who have been infected with the HPAI H5N1 strain, most have had close contact with infected poultry.
"The ability of the virus to jump to humans is not effective," said Kumnuan Ungchusak, director of the bureau of epidemiology at Thailand's Ministry of Health in Bangkok.
But that could change, through a process called viral reassortment.
An avian-flu virus and a human-flu virus might infect the same host animal, such as a pig or even a human. If so, the two flu strains may swap genes and produce a new hybrid strain.
"The influenza virus can switch in new genes at the drop of a hat," said Hon Ip, director of the virology lab at the U.S. Geological Survey in Madison, Wisconsin.
A new deadly virus may combine human-flu virus genes that allow efficient human-to-human spread with a gene from the bird-flu virus against which humans have no immunity.
"A combination of a highly pathogenic [bird flu] virus with the genes for efficient human spread is likely to have pandemic potential," Ip said.
The culprit of the influenza pandemics of 1957 and 1968, which together killed almost two million people, was a virus created from the mixing of bird-flu and human-flu genes.
Asian farms may serve as a viral breeding ground.
"The close proximity of poultry, pigs, and humans in the backyards of billions of families in Asia allows numerous opportunities for this to happen," said Kwok-yung Yuen at the Center of Infection at the University of Hong Kong.
"The cells of poultry, pigs, and humans can be infected by both human and avian viruses" at these farms, he said. (Also see "Cats Can Catch and Spread Bird Flu, Study Says.")
But the avian-flu virus can also mutate on its own, and could transform itself into a lethal human infection.
Viral mutations occur all the time. The H5N1 virus has in fact undergone huge genetic changes and become more pathogenic, or disease causing, since it first emerged.
"It can replicate much more effectively than a human-flu virus," said Aldis, the WHO official.
Researchers have studied tissue samples of victims of the 1918 "Spanish flu," which killed as many as 50 million people around the world.
The scientists concluded that an avian-flu virus like H5N1 had caused the pandemic. It had mutated and jumped into humans, they said. (See "'Bird Flu' Similar to Deadly 1918 Flu, Gene Study Finds.")
After rebuilding the 1918 virus in a laboratory, scientists found that the Spanish-flu virus spread extremely fast.
"The worst case that we can expect would be the emergence of a virus like that one," Aldis said.
"Some in our scientific community believe that reassortment is necessary, based on historical precedents (and one can easily envision scenarios as seasonal flu goes around)," Stephen Morse, an epidemiologist at Columbia University in New York and author of Emerging Viruses, wrote in an e-mail interview.
"But others argue that accumulation of a few critical mutations may be enough," he said. "The reality is, we don't really know with any certaintywe are in terra incognita, and we're really not sure what the rules are."
Although predicting pandemics is difficult, there is some evidence that they happen three to four times every century.
Many health officials believe the world is now closer to another influenza pandemic than at any time since 1968.
Most experts believe the prompt culling of Hong Kong's entire poultry population in 1997 probably averted a pandemic.
But no one knows what would happen if an H5N1 virus adapted to grow in humans. It might be as lethal as it is now, or it might become far less pathogenic.
"Human adaptation might be at the cost of pathogenicity," said Ian Jones, a virologist at the University of Reading in England.
It may just burn out and go away.
"The best case would be that we have a virus capable of transmitting from human to human, but it would not be very lethal," the WHO's Aldis said.
"Maybe we'll have an emergent avian virus and the result is just a bad flu season."
Free E-Mail News Updates
Sign up for our Inside National Geographic newsletter. Every two weeks we'll send you our top stories and pictures (see sample).
SOURCES AND RELATED WEB SITES