Of mice and men: role of mice in biomedical research questioned

Christopher Degeling, University of Sydney and Jane Johnson

A study recently published in the peer-reviewed journal PNAS (Proceedings of the National of Academy Sciences) shows that mice are poor models for human inflammatory diseases. The paper, which focused on sepsis, burns and trauma, raises questions about the fundamental role of mice in biomedical research.

Bodily responses to burn injuries and acute infections look similar in mice and humans, but the study authors found they’re driven by fundamentally different genetic and molecular mechanisms. They spent ten years examining which genes in human white blood cells are activated during infection. Data from 167 patients suggested there are particular patterns of genomic change associated with acute inflammation.

After having their paper rejected by several journals, the researchers decided to redesign their study. Apparently, one objection from reviewers was that the results had not been validated by mouse studies. But when the researchers looked at the genomic response to different forms of inflammation in mice, they made a number of startling discoveries:

  1. The relatively uniform gene changes found in human patients were not found in mice.
  2. Genomic changes in mice were completely different to humans, and there was no discernible pattern of gene modification.
  3. None of the mouse models for sepsis, bacterial blood poisoning, trauma or burns predicted the magnitude or direction of inflammation in humans.

These findings have significant ramifications.

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