Bird flu may mutate to menace humans

PHILADELPHIA – Using new genetic information from the deadly 1918 Spanish influenza, scientists say the lethal avian flu plaguing Southeast Asia could evolve in a similar way to become a global human menace.

Up to now, many people thought the bird virus would need to mix with a human virus before it could become a pandemic strain.

But now, scientists believe it also could undergo its own genetic changes and morph into a version that would spread easily among people, according to an article in this week’s issue of the journal Nature.

The present flu strain, which has infected more than 100 people and killed at least 60, mostly in Vietnam, already has experienced several changes that mimic those in the 1918 virus, according to Dr. Jeffery Taubenberger, the study’s lead author.

“It makes the situation scarier,” said Taubenberger, chief of the Molecular Pathology Department at the Armed Forces Institute of Pathology, whose work enabled the 1918 flu virus to be recreated. “It means that the 1918 way of forming a pandemic could happen again.”

Public health officials have watched with growing alarm as the avian virus has spread over much of Asia, killing millions of birds along the way. U.S. government leaders have become edgy, too, and stepped up pandemic preparations by starting to stockpile antiviral drugs and funding vaccine development against the avian flu. And President Bush said this week he may call upon the military to enforce quarantines if a pandemic hits the United States.

So far the avian strain hasn’t jumped readily from birds to humans. Flu becomes a pandemic when a new strain arises and easily infects people because they lack the immunity to fight it. The 1918 pandemic infected one third of the world’s population and killed up to 50 million people.

“Most experts agree, it’s not a question of if but when,” Dr. Julie Gerberding, head of the U.S. Centers for Disease Control and Prevention, said Tuesday during a telephone press conference to discuss the Nature paper and a separate article appearing this week in the journal Science.

In the Science paper, researchers described the first recreation of the 1918 virus. To decipher the genetic code, researchers said they used lung autopsy material from 1918 pandemic victims, including an Alaskan buried that year in the permafrost.

They used the strain’s newly deciphered gene sequence and “reverse genetics” – a technique that makes certain viruses from DNA.

In tests, the recreated live virus – which researchers say is housed safely at the CDC – grew quickly in human lung cells and caused rapid death in mice. The authors added that no other human influenza virus has shown the same disease-causing abilities in mice.

Terrence M. Tumpey, a senior CDC microbiologist who led the study, said the work will help scientists develop new drugs and vaccines to prevent a pandemic. Their tests indicated that some existing antiviral drugs and vaccines were effective in Spanish flu.

Making a live virus raised safety questions both for the lab workers and the public. Some fear that the findings could be used by terrorists.

The rationale for doing the work and publishing it is to encourage more research “at a time when we desperately need to engage the scientific community and accelerate our ability to prevent pandemic influenza,” said Gerberding and Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, in a joint statement. “It would be impossible and counterproductive to attempt to enforce a worldwide ban on conducting research on the 1918 influenza virus or similar viruses because of fear of the misuse of such knowledge.”

The research has helped unlock mysteries about the 1918 virus, they said, by identifying gene sequences that could predict a new virulent flu strain. It also has found genes “most likely to account for the lethal effects of the 1918 virus.”

In the Nature study, researchers completed the genetic sequencing of the 1918 virus using lung tissues of pandemic victims. They discovered it probably formed differently from the viruses in the other two 20th-century pandemics in 1957 and 1968. Those strains emerged through the genetic combination of influenza viruses from humans and birds.

“Now what we are saying is there is another path,” Taubenberger said.

“This is the first clear evidence that demonstrates that all pandemics are not the same,” said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota.

Taubenberger’s team identified a small number of genetic changes in the 1918 virus that could help explain how the bird virus adapted to humans.

Today’s avian flu viruses also would need to undergo similar mutations to become a pandemic strain, Taubenberger said. So far, he said, no single viral isolate has shown more than one of these crucial changes. But if one started to accumulate multiple mutations, he said, a pandemic could follow.

“It doesn’t take a rocket scientist to understand that is what is happening in Southeast Asia,” Osterholm said. “Everything on the genetic roulette table favors it doing what it is doing.”

Taubenberger said the new understanding could help scientists identify a mutating virus more quickly and try to keep it from spreading among people. For instance, if it popped up at one farm or village, public health workers could try to depopulate the chickens in the region and give people anti-viral medicine.

“Nobody can predict the future,” Taubenberger said. “This gives us a better opportunity to try to stop the avian virus.”