ASIA     Lessons from History
	Will the Next Pandemic Rival 1918?
	By BRYAN WALSH

In Philadelphia, bodies lay uncollected for days, until horse-drawn carriages were sent through the streets and the call came for the living to bring out their dead. In Cape Town they ran out of coffins and tossed corpses wrapped in blankets into mass graves. Thousands of American soldiers at sea died in troop transports that became known as death ships. Their bodies were tipped into the Atlantic to avoid infecting survivors, but nothing could halt the spread of the virus. "If the epidemic continues its mathematical rate of acceleration," wrote a prominent U.S. public health official, Dr. Victor Vaughn, "civilization could easily disappear [within] a few more weeks."

This was the horror of life during the Spanish flu pandemic of 1918, a year that serves as a chilling reminder to every infectious-disease expert of just how catastrophic a pandemic can be. The Spanish flu likely infected more than 30% of the world's population and may have killed up to 100 million people. In 24 weeks, it took more lives than AIDS has in 24 years. "It was a perfect storm for a terrible epidemic," says Dr. Howard Markel, a medical historian at the University of Michigan.

But is it a storm that could strike again? When public health officials warn that an avian flu pandemic could take tens of millions of lives, they're assuming the return of a 1918-strength virus. It wasn't just the enormous death toll that made 1918 stand out, though, but who died and how. While flu usually kills only the very young or old, in 1918 those aged 20 to 40 were the most vulnerable. That may have been because the Spanish flu, unlike weaker flus, could apparently trigger a fatal overreaction by the body's own defenses. Immune cells would tear apart infected tissue in an effort to destroy the virus, a process called a cytokine storm, and blood and other fluid carrying those cells would pour into the lungs, triggering acute respiratory distress syndrome (ARDS). Young adults, who have strong immune systems, would have been most at risk for such biological blowback.

The unusual virulence of the 1918 virus may stem from the fact that it evolved amid the unique mayhem of World War I. According to Paul Ewald, an evolutionary biologist at the University of Louisville, crowded, unhygienic conditions — tens of thousands of troops stuffed into transport ships, trenches and military hospitals — favored the evolution of a "predator-like virus" that would have killed too quickly to be easily transmissible in a normal environment. Troops sickened and died but were so densely packed that they could still spread the super-strong virus onwards, even from a hospital bed. The pandemic viruses of 1957 and 1968, by contrast, were about as transmissible as the 1918 strain but were much weaker — in Britain fewer people died from flu in 1968 than in the year before. "I think we will never again see a pandemic with mortality like 1918," says Ewald. "If H5N1 began to be transmitted from human to human, I expect it would evolve toward lower virulence."

Pessimists counter that the effects of H5N1 seem to resemble those of the Spanish flu, including evidence of cytokine storms and ARDS, and note that no one can predict what a new strain of the flu might bring. "Nothing in influenza is surprising to me, because the one thing you can be sure of in influenza is its unpredictability," says Malik Peiris, a virologist at the University of Hong Kong. The 1918 flu made that clear. As it burned its way around the globe, Vaughn ruefully told a colleague: "Never again allow me to say that medical science is on the verge of conquering disease." That battle was lost, and the war is far from over.

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