Using lung tissue from long-dead victims, researchers hoping to prevent another flu pandemic said they have reconstructed one of history's deadliest pathogens - the 1918 Spanish flu virus.
The Spanish flu began as a virus in birds before jumping to humans and killing an estimated 20 million to 50 million people worldwide. Determining why it was so lethal and how it spread could help scientists blunt the threat posed by the avian flu in Asia and future variations.
"We have been able to unmask the 1918 virus, and it's revealing to us some of the secrets that will help us predict and prepare for the next pandemic," said Dr. Julie L. Gerberding, director of the federal Centers for Disease Control and Prevention, where the virus was reconstructed.
Researchers followed strict safety guidelines for working with infectious diseases, according to the agency, including wearing battery-powered air filters and showering when they left the lab. Gerberding said the research benefits outweigh the risk of accidental exposure to the virus.
Two journals, Science and Nature, are publishing accounts of the research today and tomorrow. Experts in the field were quick to praise it.
"My reaction to this is, wow. Just, wow," said Dr. John Treanor, a flu vaccine researcher at the University of Rochester Medical School in New York.
Researchers replaced some of the proteins found in the 1918 virus to see how they affected its virulence. They also compared the genetic structure of the 1918 flu strain to strains that have evolved since then and infect birds and humans.
"There is some parallel evolution going on," said Jeffery Taubenberger, a co-author and researcher at the Washington-based Armed Forces Institute of Pathology.
Taubenberger reconstructed the virus genome using tiny bits of genetic material fished out of infected tissue in the lungs of military personnel whose remains are kept in wax at the institute. He also used lung tissue samples from a female flu victim buried in the Alaskan permafrost in 1918, identified only as Lucy, whose remains were dug up by a researcher in 1997 with permission from local authorities. In other Spanish flu studies, British researchers traveled to Norway in 1998 to retrieve frozen tissue samples.
Taubenberger said the results show that the 1918 virus was an avian virus that adapted to humans. By contrast, the 1957 and 1968 flu strains that killed tens of thousands of people originated in humans.
How viruses make such adaptations will be the focus of future studies, he said.
"It suggests that pandemics can form in more than one way," Taubenberger said.
The study also identified several genes that play a key role in virulence: three genes that encode enzymes that control how the virus replicates, and a gene that encodes the protein that helps the virus replicate, attach to cells and damage the lungs of those infected.
Dr. James Campbell, principal investigator for an avian flu vaccine clinical trial at the University of Maryland School of Medicine, said the study shows that the genetic makeup of the 1918 flu strain enabled it to infect lung tissue without trypsin, an enzyme in lungs and other organs that other viruses need to spread infection.
He said a key question not resolved by the study is what transformations would make the Asian flu virus, that is so lethal in birds, transmittable among humans.
"The fact that they sequenced its genetic code and reconstructed the virus in a lab is a major step," he said.
Gerberding said the reconstructed virus is safely confined to vials at the CDC campus in Atlanta.
She also said a flu strain infecting people - known as H1N1 - is a descendant of the Spanish flu, and so most people have immunity and wouldn't be threatened by exposure. In any event, today's flu medications would likely be effective in combating it, she said. But she also said nothing can be certain in flu virus research and said that's why CDC staff followed the safety guidelines established for handling infectious diseases.
But other experts said that because flu viruses mutate, it is not clear how well our immune systems or medications would respond to the 1918 strain.
"The H1N1 we see today is probably so different from the 1918 H1N1 that it's hard to say how much protection we'd have," said Earl Brown, a virologist at the University of Ottawa.
Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said the National Science Advisory Board for Biosecurity, a Department of Health and Human Services advisory group, agreed that the study and the virus genetic code should be made public because researchers need access to them.
"It was very clear that the scientific benefit of this far outweighed potential for use in a nefarious manner," Fauci told reporters.
There have been 10 influenza pandemics in the past 300 years, and many health officials say another pandemic is inevitable.
The avian flu strain is racing through bird populations in Southeast Asia and could touch off the next pandemic, experts say. Since December 2003, the virus has killed more than 60 people and led to the slaughter of millions of infected chickens and other birds. Human cases have been reported in Thailand, Vietnam, Cambodia and Indonesia.
H5N1 has been unable to pass easily from person to person. Most of the fatalities stem from contact with poultry.
A flu virus contains two proteins, hemagglutinin and neuraminidase. Together they form large spikes on the surface of the virus. People develop immunity by creating antibodies that fight them off.
But mutations in the genes that code for the proteins can change the protein structures, throwing off the body's immune system. Such changes could trigger a pandemic.
"Most experts agree it's not a question of if, it's a question of when," Gerberding said.