A Mouse is a Mouse is... Not a Human

Neurobiologists at the Allen Institute for Brain Science in Seattle may have uncovered one of the reasons why 90 percent of drugs that succeed in mice fail in humans. In a study published in the journal Nature (Hodge et al., 2019), the scientists analyzed nearly 16,000 neurons from the outermost layer of the human brain. Using new technology, they classified the brain cells not by shape and location (the traditional method) but by the genes they express—how they use DNA to create neurotransmitter receptors and other critical elements of the brain. The scientists then compared the results to those from mouse brains. 

They found that neurons long thought to be the same in humans and mice, based on traditional measures, can have vast differences in gene expression. The difference is particularly important for the genes that encode (i.e., produce) receptors for the neurotransmitter serotonin, a chemical involved in depression, sexual function, and appetite. “If the neurotransmitter receptor you’re hoping to target isn’t used in the same cells in humans that it is in mice, then your drug will hit the wrong circuit,” said study co-author Ed Lein. The study’s findings challenge the use of mouse models for studying psychiatric disorders involving serotonin, and highlight the importance of directly studying human brains.

Share This!