Scientists have decoded the genetic structure of the influenza virus that killed tens of millions of people soon after World War I. The research fulfills more than a mere historical curiosity. With fears about an impending pandemic from avian flu, the work provides insight into the structure of killer flu viruses that might lead to better medicines against them.
It was the 20th century's greatest plague. Estimates of the 1918-1919 flu death toll range from 20 million to 50 million, more than died in the war that had just preceded it.
The head of the U.S. government's disease tracking agency, Julie Gerberding of the Centers for Disease Control, says hardest hit were the young and productive between 20 and 40 years old.
"The 1918 influenza virus that caused such global global disease spread very rapidly, particularly among healthy people, was very, very virulent, and certainly circled the globe in record time," she said.
U.S. government and private scientists have finished a 10-year project to determine the virus' genetic makeup. They recreated a live virus in a high-security laboratory at the Centers for Disease Control (CDC) by combining fragments from the organism's eight genes.
Researcher Jeffrey Taubenberger of the Armed Forces Pathology Institute says the genetic scraps were gathered from well preserved lung tissue samples taken from victims during autopsies 87 years ago or, in one case, from a victim exhumed from Alaskan permafrost.
"Because influenza viruses were not known to exist in 1918, there were no isolates made of this strain of the virus, and so there was actually no way for medical scientists to directly study this influenza virus," he explained.
The scientists tested the virus by inserting it into mice, chicken embryos, and human lung cells. They found that by substituting genes from other flu viruses, they could make it less lethal.
The research, published in the weekly journals Science and Nature, shows that the 1918 flu virus is more closely related to bird flus than human flus. It has several of the same genetic mutations found in the bird flu strain now spreading in Asia, mutations believed to help the virus replicate more efficiently.
Mr. Taubenberger says this reveals that bird flu viruses can cause serious human infection without first combining with a strain already adapted to people. Some experts have said that effective human transmission might require combination with a human flu.
"We now think that the 1918 virus was an entirely avian-like virus that adapted to humans," said Mr. Taubenberger. This is a different situation than the last two pandemics we had, the Asian flu in 1957 and the Hong Kong flu in 1968, which are mixtures in which a human-adapted influenza virus acquired two or three new genes from an avian influenza source. So it suggests that pandemics can form in more than one way, and this is a very important point."
He says it also suggests that the current Asian bird flu, known by its scientific designation H5N1, could evolve into a human killer with just a few more mutations that allow it to jump more efficiently among people.
"It suggests to us the possibility that these H5 viruses are actually being exposed to some human adaptive pressures and that they might be acquiring some of these same changes," he added. "In a sense, they might be going down a similar path that ultimately led to 1918."
Mr. Taubenberger says if researchers can identify virus components that are important in the process of adapting to humans, they could make a list of molecules to look for in emerging bird flus that threaten people.
Dr. Gerberding of the Centers for Disease Control says the work will allow new medical therapies to target those molecules.
"It is revealing to us some of the secrets that will help us predict and prepare for the next pandemic," she said.
Dr. Gerberding says it is comforting to know that the 1918 virus, now that it has been reconstructed, is susceptible to a new vaccine U.S. researchers have developed against bird flu. This means it should work against the bird flu, too, if production can be expanded should a pandemic occur.
