The strain of avian influenza virus 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 genetic changes typical of the "Spanish flu" virus that killed 50 million people nearly a century ago, researchers said yesterday. How far bird flu virus has traveled down the evolutionary path to becoming a pandemic virus is unknown. Nor is it certain that the much-feared strain, designated as 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 the H5N1 strainslowly spreading through Asia provide unusually concrete evidence of how dangerous the newer bird flu virus is. At least four of its eight genes now contain mutations seen in the deadly strain that circled the globe during and after World War I.
The HSN1 Virus under a microscope
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 bird flu virus is the first practical use of a science-fiction-like scenario that concluded yesterday with the release of two papers, one by the journal Science and the other by its chief competitor, Nature.
After 10 years of work, Taubenberger and his team succeeded in reconstructing the Spanish flu virus, which was 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 in Atlanta, the pathogen appears in animal experiments to be as lethal as it was in humans 87 years ago.
The report came as the United States, many other countries and the World Health Organization are making increasingly urgent preparations for a new flu pandemic.
The Department of Health and Human Services is stockpiling antiviral drugs and is buying enough experimental bird flu vaccine to inoculate 20 million people,should the bird flu virus take hold. President Bush said in a news conference this week that he is considering the use of the military to enforce quarantines, if necessary, and that the government's long-awaited pandemic plan will be released soon.
What makes the accomplishment reported yesterday so remarkable 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 did not know for certain what caused it. (The influenza virus was not identified until 1933.) Although biologists were later able to deduce the broad family of influenza viruses the 1918 strain came from, its genetic identity was lost.
Taubenberger and his colleagues were able to piece together the 1918 virus's genes from two unconventional sources. One was fingernail-size pieces of lung tissue, preserved in wax after the autopsies of two 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 reconstruction of the 1918 virus is expected to provide immediately useful insights to epidemiologists studying the kind of bird flu virus that is being passed among dozens of species of birds and mammals worldwide.
"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 1918 virus differs genetically from related viruses that do not infect people, researchers hope to pinpoint the mutations an animal flu virus needs to acquire to adapt to human beings. Taubenberger estimates, as a rough guess, that 25 mutations may be essential
It will be especially useful to compare the 1918 gene sequence to those of the two flu viruses that have caused pandemics since then -- the "Asian flu" of 1957 and the "Hong Kong flu" of 1968. Hybrid viruses containing genetic features of each can then be constructed and studied in the laboratory.
The researchers believe adaptation to humans requires six changes in another gene, called nucleoprotein. H5N1 strains have been found carrying one. In yet another gene -- for a protein called matrix -- four changes appear necessary. Surveillance has turned up H5N1 strains carrying two of the four.
Altogether, the changes suggest that though H5N1 is still a bird flu virus, it is partway along a path to becoming a human virus.
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The strain of avian influenza virus 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 genetic changes typical of the "Spanish flu" virus that killed 50 million people nearly a century ago, researchers said yesterday. How far bird flu virus has traveled down the evolutionary path to becoming a pandemic virus is unknown. Nor is it certain that the much-feared strain, designated as influenza A/H5N1, will ever acquire all the genetic features necessary for rapid, worldwide spread. 
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.
By identifying how the 1918 virus differs genetically from related viruses that do not infect people, researchers hope to pinpoint the mutations an animal flu virus needs to acquire to adapt to human beings. Taubenberger estimates, as a rough guess, that 25 mutations may be essential