More people perished from the influenza pandemic of 1918 than were killed during World War I. In 18 months, the deadly flu seized 50 million to 100 million lives.

Nearly 90 years later, researchers may know why this strain of flu was so lethal. As reported in the Jan. 18, 2007, issue of Nature, an international team of researchers discovered the virus triggered an autoimmune response in an infected person - a response that attacked the lungs rather than the viral infection, eventually filling the lungs with fluid and drowning the victims.

Yoshihiro Kawaoka, professor of pathobiological sciences at the University of Wisconsin-Madison and an expert on the influenza virus, teamed with Canadian, American and Japanese researchers to introduce a genetically engineered version of the 1918 influenza virus into seven monkeys. They also infected three other monkeys with a "control" human influenza. To guarantee infection, each monkey received several million units of flu - either the 1918 version or the control version.

The monkeys infected with the conventional flu showed few clinical signs of respiratory infection, all of which were mild. However, the seven, 1918 virus-infected animals became ill within 24 hours, and their condition worsened dramatically as hours passed. Ethical guidelines forced the researchers to euthanize them within eight days of the initial infection to analyze how the two flu strains affected their tissues and organs. Their lungs were bloated, bloody and filled with fluid - similar to the pathology reports of 1918 flu victims.

Some of the damage is similar to the Southeast Asia avian influenza in that both flu strains ravage the upper and lower respiratory tracts, unlike the conventional flu, which affects the upper respiratory tract.

Based on these similarities, the researchers hope to develop medicines should another lethal influenza pandemic occur.