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Stanford Immunologist Calls For More Research On Humans, Not Mice

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Mouse Trap? Stanford Immunologist Calls For More Research On Humans, Not Mice

27 Dec 2008

The fabled laboratory mouse-from which we have learned so much about how the immune system works-can teach us only so much about how we humans get sick and what to do about it, says a leading researcher at the Stanford University School of Medicine.

The time has come for immunologists to start weaning themselves from experimental rodents and to embark on a bold, industrial-scale assault on the causes and treatment of specifically human disease, writes immunologist Mark Davis, PhD, in an essay to be published Dec. 19 in Immunity. Davis, director of the Stanford Institute for Immunity, Transplantation and Infection, proposes that the current mouse-centered, small-laboratory approach be supplemented by a broad, industrial-scale "systems biology" approach akin to the one that unraveled the human genome.

"We seem to be in a state of denial, where there is so much invested in the mouse model that it seems almost unthinkable to look elsewhere," Davis, the Burton and Marion Avery Family Professor and professor of microbiology and immunology, writes in the essay.

Over the past several decades, the little mouse has proven immensely helpful in generating a fundamental understanding of how the mammalian immune system works, Davis said in an interview. "The mouse has been incredibly valuable," he added. "That's part of the problem."

Experimental manipulations that are commonplace with lab mice, such as genetically engineering them to express a foreign protein or to be deficient in the expression of one of their own, would be unthinkable in a human. Because experimental mice can be used to get quick answers, Davis argues, researchers look to the mouse to tell them everything. "In humans it often takes years to find out anything. There are a lot more regulatory, financial and ethical hurdles," he said.

But when it comes to adapting therapeutic interventions that seem to cure all kinds of infectious disease, cancers and autoimmune conditions in mice for use in human beings, the record is not so good. The vast majority of clinical trials designed to test these interventions in people end in failure.

"Mice are lousy models for clinical studies," Davis asserts in his essay.

There are probably some good reasons for this, said Davis. For starters, mice are rodents, separated from humans by some 65 million years of evolutionary divergence from our common ancestor.

That's not all. While it takes about 20 years for a person to reach sexual maturity, a mouse gets there in three months. The roughly 100 years during which the furry, diminutive animals have been domesticated and bred in labs are, therefore, the mouse equivalent of 8,000 human years, during which they have been inbred and kept relatively disease-free. They would never survive in the wild, said Davis.

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