Avian Flu Virus Growing Similar to Lethal 'Spanish Flu'
Wednesday, October 5, 2005; 4:21 PM
The strain of avian influenza that has led to the deaths of 140 million birds and 60 people in Asia in the past two years appears to be slowly acquiring the genetic changes characteristic of the "Spanish flu" virus that killed 50 million people nearly a century ago.
How far "bird flu" has traveled down the evolutionary path to becoming a pandemic virus is unknown. Nor is it certain the worrisome strain, designated influenza A/H5N1, will ever acquire all the genetic features necessary for rapid, worldwide spread.
Nevertheless, the similarities between the Spanish flu virus of 1918 and H5N1 strain slowly spreading through Asia provides unusually concrete evidence of how dangerous the latter virus is.
"These H5N1 viruses might be acquiring the ability to adapt to humans, increasing their pandemic risk . . . there is a suggestion there may be some parallel evolution going on," said Jeffery K. Taubenberger, a molecular pathologist at the Armed Forces Institute of Pathology in Rockville.
The comparison of the old and new influenza viruses is the first practical use of an extraordinary accomplishment whose completion was announced today in two papers, one published in the journal Science and the other in its chief competitor, Nature.
After 10 years of work, Taubenberger and his team reported they had successfully reconstructed the Spanish flu virus, responsible for the deadliest epidemic since the Black Death of the Middle Ages. "Reborn" in mid-August at a high-security laboratory at the Centers for Disease Control and Prevention, the pathogen has already been shown in animal experiments to be just as lethal as it was out in the world 87 years ago.
What makes the accomplishment so unusual is that no intact samples of the Spanish flu virus exist. When the pandemic occurred in 1918 and early 1919 -- only American Samoa and parts of Iceland appear to have been spared -- microbiologists didn't know for certain what caused it. (Influenza virus wasn't isolated and identified until 1933.) While biologists were able to deduce the broad family of influenza viruses the 1918 strain came from, Spanish flu's genetic identity was lost.
Taubenberger and his colleagues, however, were able to piece together the virus's genes from two unusual sources. One source was fingernail-size pieces of lung tissue removed at autopsy from two American soldiers who were among the pandemic's 675,000 American victims. The other source was the frozen body of an Inuit woman who died of influenza in November 1918 and was buried in the permafrost.
The virus's eight "gene segments" -- strands of RNA that are the equivalent of DNA and chromosomes in cells -- were in pieces, like a shelf of ancient vases tipped onto a stone floor. But with gene sequencing and the polymerase chain reaction -- the magnifying glass and glue of molecular genetics -- Taubenberger and his colleagues reassembled the infamous microbe.
"It is an amazing feat," said Edwin D. Kilbourne, 85, one of the country's leading influenza virologists and a retired professor from Mt. Sinai School of Medicine and New York Medical College. "It's a tribute to imagination, perseverance, and a great deal of very hard work."
Far from being an elaborate scientific parlor trick, the reconstruction of the 1918 virus is expected to provide insights that are immediately useful to the virologists and epidemiologists charting the flow of hundreds of flu strains through dozens of species.
"I think we have been able to unmask the 1918 virus, and it is revealing some of the secrets that will help us prepare for the next pandemic," said Julie L. Gerberding, director of the CDC.
By identifying how the Spanish flu virus differs genetically from related flu viruses that don't infect people, researchers hope to identify the mutations that are necessary for adaptation to a human host. Taubenberger estimates, as a rough guess, there may be 25.
"It could theoretically provide a checklist for surveillance," he said. "You might be able to say: this strain has six of these changes; it's a worrisome virus we need to keep our eye on. Or this one has none."
At the least, the reconstructed virus increases by one-third the archive of microbes that have caused flu pandemics.
It will be especially useful to compare the 1918 virus gene sequence to those of the "Asian flu," which emerged in 1957, and the "Hong Kong flu," which circled the globe in 1968. Hybrid viruses containing genetic features of each in different combinations can then be constructed and studied in the laboratory.
"We are trying to elucidate the general rules of human adaptation. How does a bird virus become a human virus? Generically put, that is what we're trying to answer," Taubenberger said.