This Is Why It's A Mistake To Cure Mice Instead Of Humans
Elbert Chu
at 07:30 AM Feb 14 2013
This Is Why It's A Mistake To Cure Mice Instead Of Humans
Wild Lab Mouse Turns out they're nothing like humans, sometimes.
Tambako the Jaguar
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The good news for mice is that humans have spent billions of dollars to solve their illnesses. But it seems researchers have tortured mice in vain for decades in the search for drugs to help humans recover from certain traumas, like severe burns, blunt force, and sepsis. Mouse genes just don't react the same way as human genes in all cases - in fact, sometimes they are contrary to one another. But we shouldn't get rid of our fuzzy friends entirely.

A whopping 39 researchers representing dozens of schools (including Stanford, Harvard, and the University of Florida) have found genetic evidence that mice aren't anything like people in some important cases. The science community shouldn't necessarily be shocked by the finding; we've been aware for awhile that mice may not be a precise analogue for humans. What makes this study interesting is that the doctors have studied specific diseases to find out exactly how widely the genetic response diverges between mice and men.

This study was birthed out of rejection. The researchers' original work focused on human white blood cells' genetic response to life threatening traumas. But when an undisclosed journal demanded they verify the findings in mice, the researchers started wondering if that would actually prove anything. So they began to dig deeper, and the study became more about mice than the original study. The researchers published this study in the Proceedings of the National Academy of Sciences this month.

The scientists analyzed a decade of research from trauma centers. They looked to lab data for mouse genes changes after severe burns, blunt trauma, or sepsis. Of particular interest was which genes cells turned on after burns, trauma like car accidents, and sepsis. Sepsis is an overreaction by the immune system to microbes or human proteins - it's almost like the body self-destructs, causing a cascade of responses that ends with a rapid and severe drop in blood pressure that can lead to organ failure.

Researchers even injected four healthy volunteers - yes, human volunteers - with low doses of bacterial toxins to monitor gene response. Then they compared this with genetic data from mice they afflicted with similar troubles. By the end of the study, the researchers looked at some 5,000 genes that overlap humans and mice. The genetic changes similar in both people and mice barely hit the 50 percent neighborhood, which is like random chance. One gene activated in mice, were not even expressed in humans. Another gene that helped mice recover, harmed humans.

Scientists now are beginning to understand why 150 of the drugs that worked in mice for sepsis failed when tested on humans. And that's incredibly valuable; researchers may be wasting millions of dollars and years of resources working on cures that work on mice, when those same cures may not work on humans.

Bear in mind, this research only applies to these three diseases, so in some cases mice do prove good analogs. Still, there may be implications for other illnesses that involve genes, like cancer, that are studied extensively in mice. The clear takeaway is that scientists need to evaluate molecular models more closely when choosing test subjects. Volunteers for lab humans?

[New York Times]

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