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February 20, 2009

We’re Too Fixated on Mice, Says Leading Researcher

Studying mice has limited relevance when it comes to treating or preventing diseases in humans

The Humane Society of the United States

  • research mouse

    Experiments on mice tell us more about how to treat artificially induced diseases in mice than actual diseases in humans. iStock.com

When it comes to accurately predicting how the immune system will react to new therapies against disease, using a mouse as stand-in for a human just doesn’t cut it anymore.

But, despite the obvious pitfalls and failures of the heavy focus on mouse biology, researchers are in a state of denial when it comes to switching to more advanced methods.

That's the message of an essay written by a leading researcher at the Stanford University School of Medicine and published on December 19, 2008 (volume 29, issue 6) in the journal Immunity.

In "A Prescription for Human Immunology", Mark Davis, PhD, director of the Stanford Institute for Immunity, Transplantation and Infection, says that the benefits to understanding and treating human diseases could be huge if researchers shifted from mouse experiments to studies of human blood and tissue samples.

"To fully realize the potential benefits of immunology for human health, we need to place more emphasis on human studies and make greater efforts to allow it to flourish," he writes.

Fundamental Limitations

Davis argues that although studies of laboratory-bred mice have made historical contributions to understanding the fundamentals of the immune system of mammals, the value of their use in clinically oriented studies—researching potential therapies for human diseases—is undermined by the differences between mice and humans.  

He argues that lab-bred mice—the animals most commonly used in research—typically live in sterile conditions that are very different from the environment that humans live in, so results from mice may not accurately mirror results in humans.

Another disconnect is the vast difference in the timing of sexual maturity that exists between humans and mice, which can make it difficult to relate results in mice to humans.

"Mice are lousy models for clinical studies," Davis writes.

Indeed, the vast majority of clinical trials designed to test treatments for cancers, infectious diseases and autoimmune conditions have failed.

The limitations of using animals in experiments that are designed to assess outcomes in people are not confined to mice, nor confined to disease-oriented research. The problems that scientists encounter when attempting to use animals like monkeys, rabbits, dogs, rats, and other animals to predict how a human body will react to commercially produced chemicals, for example, are well-documented.  

So why keep clinging to something that's not working? Davis thinks researchers were wowed by the early success of mice studies in revealing the basics of the immune system, and are now failing to appreciate their lack of success in more clinically oriented studies. 

"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," he writes.

But Davis is convinced that any progress in using the body's immune system to combat disease will stem primarily from modern methods, especially through applying the young science of "systems biology" to the study of human blood and tissue samples.

Intelligent Design

In his essay, Davis advocates for an effort to create a large, industrial-scale infrastructure that would allow researchers to capture information from human blood and tissue samples acquired through routine lab tests and clinical trials.

Researchers would then enter the samples into a national or international database accessible to researchers, who could study the molecular differences among people with and without disease, for example.

Turning to Alternatives

Davis's call to move towards using modern methods to directly study human biology echoes recent calls to do the same in the field of toxicity testing.

In February 2008, prominent scientists in the U.S. government published a perspective in the journal Science, urging a shift away from decades-old animal tests in favor of sophisticated—and largely non-animal—methods of assessing the effects of chemicals on people. 

"Pioneering researchers are showing how modern science can be harnessed to develop the tools to better ensure human health while moving beyond the flawed 'animal model' approach" says Martin Stephens, HSUS vice president for animal research issues. "The question now is how quickly other scientists will embrace 21st century methods."

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