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Mouse studies may lead scientists astray for sepsis, injury studies


Mice are among the most researched animals, because evidence suggests the rodents share up to 90 percent of the same genes as humans.

Thus, many medical studies, such as those looking at the effects of a new medication for heart disease or diabetes, often employ mouse models at early stages before testing on humans, as required by the Food and Drug Administration.

New research, however, suggests mice may not provide the most accurate information when it comes to studying other dangerous ailments in humans such as burns, trauma, and the deadly bacterial infection, sepsis.

"Our findings question the validity of using mouse models to mimic inflammatory conditions in humans," study author Dr. Shaw Warren, a chemical biologist and infectious disease researcher at Massachusetts General Hospital in Boston, said in a statement.

Warren and colleagues are part of MGH's Inflammatory and Host Response to Injury program which was established more than 10 years ago to investigate how the human body responds to injury. When a human experiences a burn, trauma or is exposed to a bacterial toxin, the body may respond with excessive, uncontrolled inflammation. Sepsis, for example, occurs when the body releases chemicals as part of a "systemic inflammatory response," to bacteria and other germs, according to the National Institutes of Health, causing blood pressure to drop until the body goes into shock. This can lead other major organs to stop working properly because of the lack of blood flow, and cause death. People with chronic diseases such as diabetes, AIDS or cancer or those who suffer physical trauma or a severe burn can get sepsis.

Previously, the group of researchers had reported that serious injuries set off a "genetic storm" in the human body, affecting 80 percent of normal gene expression patterns.

For the new study, published Feb. 11 in Proceedings of the National Academy of Sciences: Early Edition,  researchers reviewed previously collected data from more than 20 research centers on inflammation in mouse models along with human studies conducted on burn and trauma patients, and studies conducted on healthy volunteers exposed to bacterial toxins. Their analysis showed that humans affected by these injuries showed similar patterns of highly significant changes to more than 5,500 genes, but there was little correlation for these changes seen in mice. Humans had more than three times as many genes affected as the mouse models and showed genetic responses up to six months after injury, while mice experienced changes in genes for a few days at most. The researchers confirmed their findings by comparing 10 studies of inflammatory disease in humans against 10 in mice, also not finding a correlation.

"Mice have been used in biomedical research for well over 50 years, in part because of the cost, size, convenience, ease of genetic manipulation and social acceptability," said Warren, who is also an associate professor of pediatrics at Harvard Medical School. "But it is often forgotten that mice appear to be much more resistant to inflammation and infection than humans."

"This is a game changer," Dr. Mitchell Fink, a surgeon and sepsis expert at UCLA, told The New York Times of the study. "When I read the paper, I was stunned by just how bad the mouse data are," he 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."