1918 Killer Flu Tested on Monkeys

WASHINGTON -- Scientists who tested monkeys with the resurrected 1918 killer flu virus now have a better idea of how the deadliest epidemic in history attacked and killed so many people _ by over-amping the victims' own immune systems.

Those findings in a first-of-its-kind experiment also help explain why so many of the roughly 50 million who died in the Spanish flu pandemic were young and healthy. Based on what was seen in monkeys, the human victims' strong immune systems likely were overstimulated, causing their lungs to rapidly fill with fluid.

"Essentially people are drowned by themselves," said University of Wisconsin virology professor Yoshihiro Kawaoka, lead author of a study being published Thursday in the journal Nature.

Scientists believe the results open a window into what could happen if the current bird flu in Asia morphs into a highly lethal strain that spreads easily among people.

The 1918 virus was reconstructed with reverse genetics, relying on tissue from victims of the early-day flu pandemic. The virus is kept only in two labs where scientists are studying it: the U.S. Centers for Disease Control and Prevention in Atlanta and the Public Health Agency of Canada's lab in Winnipeg where the monkey experiment was done.

When seven macaques were given the virus at the high-level biosafety lab there, scientists were struck by how suddenly and overwhelmingly the flu struck. The virus spread faster than a normal flu bug and triggered a "storm" response in the animal's immune systems.

Their bodies' defenses went haywire, not knowing when to stop, researchers said. The lungs became inflamed and filled with blood and other fluids.

The scientists believe the virus had the same effect on humans in 1918.

The macaque experiment was supposed to last 21 days, but after eight days the monkeys were so sick _ feverish, in pain, and struggling to breathe _ that ethical guidelines forced the researchers to euthanize them.

"There was some surprise that it was that nasty," University of Washington virologist and study co-author Michael Katze said. "It was the robustness of the immune system that helped victimize them."

The virus is very good at replicating itself, said Peter Palese, chairman of the microbiology department at Mount Sinai School of Medicine in New York. Its effect on the immune system "triggers what one refers to as a cytokine storm," he said. Cytokines transmit messages among cells in the immune system. Palese wasn't part of the study but has worked on the resurrected virus before.

No other flu virus is deadly to monkeys, and the speed in its spread and the overwhelming immune system response is similar to those in the H5N1 bird flu, Kawaoka said.