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Gene detectives reducing odds of another flu pandemic
Scripps Howard News Service


October 07, 2005

The 21-year-old Army private went into the hospital at Camp Jackson, S.C., feverish and congested on Sept. 19. He was dead from the flu little more than a week later.

In mid-November, a mail carrier arrived by dogsled at Brevig Mission, Alaska. In less than a week, 72 of the village's 80 residents were dead from the flu he brought with the mail. Missionaries buried the victims - including an obese, middle-aged Inuit woman - in a mass grave.

The soldier and the villager were just two of as many as 50 million victims of the "Spanish flu" pandemic that swept the globe in 1918-19. What makes the two notable, however, is that 87 years after they died, scientists have used virus particles from preserved samples of their lung tissue to sequence the genetic blueprint of the deadly flu, reducing the odds that a worldwide flu outbreak will ever kill so many again.

Government and university researchers used the blueprint to resurrect a live virus that contains all eight genes of the flu strain that turned many American cities into ghost towns at the end of World War I. An estimated one out of four Americans came down with the flu in less than a year, and some 675,000 died from it - most of them young adults.

"It killed so many young people that it had the effect of reducing the average life expectancy in the U.S. by more than 10 years," said Dr. Jeffrey Taubenberger, head of a research team at the Armed Forces Institute of Pathology in Rockville, Md., that's been working to retrieve and map the virus for 10 years.

The team detailed the sequence of the last three genes of the flu virus in a report published Thursday in the journal Nature. A second report on the reconstituted flu virus is being published Friday in the journal Science.

Like all flu strains, the 1918 pandemic strain mutated rapidly. Doctors at the time didn't even know a virus caused the flu - they didn't discover that until the 1930s. With no known lab samples, there was no way to retrace the flu strain.

It was only when Taubenberger came across lung specimens collected during autopsies of soldiers preserved in the institute's archives that his team was able to start teasing out details about the virus. A larger sample of material came in 1997, when retired University of Iowa researcher Johan Hultin, hearing of Taubenberger's work, returned to the chase for flu virus.

Hultin had led an expedition to Brevig in 1951 and, with the permission of local elders, retrieved lung-tissue samples from four bodies preserved in permafrost. With the lab technology available at the time, he was unable to revive the virus. Knowing what Taubenberger could do, he returned to Brevig and found the woman's body in the mass grave. Her lungs had been particularly well-preserved because her excess body fat had helped insulate them during brief periods when the permafrost had melted.

That gave the genetic detectives enough material to fully sequence the flu strain, and for other researchers at the federal Centers for Disease Control and Prevention and Mount Sinai School of Medicine to use a process called reverse genetics to reconstruct the virus' RNA.

"We felt that we had to re-create the virus and run these experiments to understand the biological properties that made the 1918 virus so exceptionally deadly," said Terrance Tumpey, a flu researcher at the Centers for Disease Control and Prevention and lead author of the Science study. "We wanted to identify the specific genes responsible for virulence, which we feel will advance our ability to prepare vaccines and make antiviral medicines that are effective against future pandemic strains."

Although the genetic data has been made part of a public database, the 10 or so vials of the virus itself - grown in human kidney cells - are contained under tight security guidelines set for potential biological weapons at the CDC's lab in Atlanta.

Of particular interest to researchers is that the 1918 flu appears to have arisen in birds and then mutated to infect and spread easily among people. The Asian bird flu that's the object of much concern among world health experts today has managed to infect people directly - and killed at least 60 - but doesn't yet have the capacity to jump from person to person.

The CDC director, Dr. Julie Gerberding, said that working with the actual virus has allowed scientists to understand the specific proteins that made the flu so deadly and transmissible. "It also provides us information that may help us identify, early on, influenza viruses that could cause a pandemic," she said.


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Contact Lee Bowman at BowmanL(at)
Distributed by Scripps Howard News Service,

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