Study questions the use of mice in medical tests

For decades, mice have been the species of choice in the study of human diseases. But now, researchers report stunning evidence that the mouse model has been misleading for at least three major killers—sepsis, burns and trauma.

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 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.

Potentially deadly immune responses occur when a person's immune system responds to what it perceives as danger signals, including toxic molecules from bacteria, viruses, fungi, or proteins released from cells damaged by trauma or burns, said Dr. Clifford S. Deutschman, who directs sepsis research at the University of Pennsylvania and was not part of the study.

The ramped-up immune system releases its own proteins in such overwhelming amounts that they make capillaries leak. The leak becomes excessive, and serum seeps out of the tiny blood vessels. Blood pressure falls, and vital organs do not get enough blood. Vital organs eventually fail.

The new study, which took 10 years and involved 39 researchers, began by studying white blood cells from hundreds of patients with severe burns, trauma or sepsis to see what genes are being used by white blood cells when responding to these danger signals.

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