Deadly 1918 flu could yield cure for future bug Research: Scientists are trying to discover what made the influenza strain so potent -- and what modern medicine can do to prevent a similar outbreak.

Sun Journal

December 16, 1997|By Douglas M. Birch | Douglas M. Birch,SUN STAFF

WASHINGTON -- It was the flu season to end all flu seasons.

In the waning days of World War I, a new strain of influenza appeared. Normally a mortal threat only to infants and the aged, this microbe was 25 times deadlier. It was often a swift and ferocious killer of otherwise healthy adults.

Between 20 million and 40 million died around the globe of the Spanish flu of 1918, probably the worst pandemic in human history. Almost a third of Americans were infected, and 675,000 died -- so many that, in a matter of months, U.S. life expectancy fell by 13 years.

Until recently, it was widely assumed that the secret of the Spanish flu's lethal nature died with its legions of victims. But earlier this year, Dr. Jeffrey K. Taubenberger and Ann H. Reid of the Armed Forces Institute of Pathology at the Walter Reed Army Medical Center announced they had discovered the shattered remains of the Spanish flu virus.

It was isolated from a sample of lung tissue, taken from an unfortunate soldier stationed at Fort Jackson, S.C., in the fall of 1918. He died that Sept. 26 at the age of 21, just five days after falling ill.

For almost 80 years, two tiny slices of the soldier's lung lay undisturbed in slabs of whiskey-colored paraffin, each smaller than a postage stamp, in institute archives. Then in 1995, institute scientists decided to hunt for the flu virus as a way of demonstrating the value of those archives, which date back to the Civil War.

"I would have suggested at the beginning that the chances of succeeding were very low," says Taubenberger, 36, of Springfield, Va., who holds both a medical degree and a Ph.D in anatomy. The hunt proved very difficult.

"It took a lot of faith and prayer to get it to work," says Reid, 38, of Washington, a research biologist. "We worked on this project for almost two years before we got a usable sample."

Viruses are very simple microbes, basically strings of genetic material wrapped up in a protein coat. The influenza virus has just 10 genes coded in genetic material called RNA; the human body's 100,000 genes are coded in slightly different material called DNA.

The Walter Reed team tracked down the pathogen by hunting for its RNA. Finally, in the summer of 1996, it discovered short segments of viral genetic material. So far, it has identified about 1,800 of 15,000 nucleotide bases -- the letters of the genetic alphabet -- that make up the Spanish flu's genetic code. Eventually, the two scientists hope to sequence them all.

The aim is to one day learn how the illness killed so efficiently and, perhaps, to prevent a new killer pandemic. But the work is proceeding slowly, slogging along like the flu season itself. "Getting [genetic fragments] from this really cruddy material, that's been difficult," Taubenberger says. "That's slowed us down a lot."

To increase the amount of material available, the Walter Reed team has tried to "immortalize" the RNA fragments by making DNA copies of them and inserting those copies into the genes of bacteria. As the bacteria multiply, they are supposed to make new copies of the flu-gene fragments. In this way, researchers could raise a library of the virus' genetic material in petri dishes.

So far, those efforts haven't succeeded. There's just too little genetic material to work with. The team could go back to the tissue samples from the soldier to harvest more gene fragments. But they've already used up half of those samples and want to conserve the rest.

They're hoping that other efforts to find more Spanish flu-infected tissue succeed. An expedition is planned for this summer to the island of Spitsbergen in the North Atlantic. A church yard there contains the graves of seven young miners who died of the Spanish flu. If they were buried beneath the permafrost, the flu virus may have survived.

Some scientists have pointed out that sequencing the Spanish flu gene probably won't immediately produce profound insights. No one knows what a "virulence gene" might look like, or how it would work.

"It's very possible that we could have the entire sequence of the virus sitting in front of us and we won't be able to tell what made it so lethal," Reid says.

But it's certainly a start. Everything there is to know about the virus is locked in its genetic structure. All scientists have to do is figure out how to interpret that structure. Eventually, scientists could manufacture individual viral genes and study how they work. But that could take years.

A shortcut to pinpointing the "killer" gene, Taubenberger says, would be to compare the Spanish flu's genetic structure to that of a closely related but less dangerous virus. Ideally, researchers would isolate a case of the flu from early 1918. The Spanish flu pandemic was actually two outbreaks. The first began in the spring of 1918, when a potent but not extraordinarily deadly virus spread through Europe and the United States. By the end of August, the killer strain of the virus appeared in Africa, the United States and Europe.

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