But now, scientists report stunning evidence that the mouse model has been misleading for at least three major killers - sepsis, burns and trauma.

As a result, years and billions of dollars have been wasted following false leads, they say.

The study does not mean that mice are useless models for all human diseases. But, its authors said, it does raise troubling questions about diseases like the ones in the study that involve the immune system, including cancer and heart disease.

"Our article raises at least the possibility that a parallel situation may be present," said Dr. H. Shaw Warren, a sepsis researcher at Massachusetts General Hospital and a lead author of the new study.

The paper, published Monday in the Proceedings of the National Academy of Sciences, helps explain why every one of nearly 150 drugs tested at huge expense in patients with sepsis has failed. The drug tests all were based on studies in mice. And mice, it turns out, have a disease that looks like sepsis in humans but is very different from the human disease.

Medical experts not associated with the study said that the findings should change the course of research worldwide for a deadly and frustrating disorder. Sepsis, a potentially deadly reaction that occurs as the body tries to fight an infection, afflicts 750,000 patients a year in the United States, kills a quarter to half of them and costs the nation $17 billion a year. It is the leading cause of death in hospital intensive care units.

"This is a game changer," said Dr. Mitchell Fink, a sepsis expert at the University of California, Los Angeles, of the new study.

"When I read the paper, I was stunned by just how bad the mouse data are," Fink said. "It's really amazing - no correlation at all. These data are so persuasive and so robust that I think funding agencies are going to take note."

Until now, he said, "to get funding, you had to propose experiments using the mouse model."

Yet there was always one major clue that mice might not really mimic humans in this regard: It is very hard to kill a mouse with a bacterial infection. Mice need 1 million times more bacteria in their blood than what would kill a person.

The new study took 10 years and involved 39 researchers from across the country.