Case Study: Mice & Sepsis

Sepsis is a potentially fatal whole-body inflammation caused by severe infection. It's the leading cause of death in ICUs, and causes millions of deaths globally each year. In the United States, sepsis affects approximately 3 in 1,000 people, and severe sepsis contributes to more than 200,000 deaths per year.

One frustrating fact is that every one of nearly 150 sepsis drugs that went to clinical trials in the past twenty years has failed. The reasons are multifaceted. However, we cannot ignore the fact that all these trials were based on initial encouraging results observed in mice.

In February 2013, an article published in the Proceedings of the National Academy of Sciences reported that “among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts.” In other words, there is no correlation between the sepsis responses at the gene expression level between mouse and human.

This finding is surprising to many, but points out a possible explanation to the consistent failures: Scientists may have been using the wrong model. According to The New York Times, “as a result, years and billions of dollars have been wasted following false leads ...”

Sepsis is not alone in this case. It's also been reported that mouse models are defective in mimicking other human diseases — for example, atherosclerosis, diabetes, and AIDS.

If the availability of genetically engineered mice but not other mammalian species positions mice as the primary animal model species, many believe it's time to revisit this. In recognition of mouse models' repeated failures in sepsis and other drug development, our researchers are embracing the emerging powerful gene targeting technologies to develop novel non-murine models.