Mice Make Imperfect Models to Study Human Maladies

Mice in a research laboratory. A recent study indicates that, at least in some instances, testing drugs on mice to determine their efficacy to treat human illnesses may be misguided. - Photo by Luis Domingo/age fotostockAn article by Gina Kolata in the February 11 New York Times titled “Mice Fall Short as Test Subjects for Some of Humans’ Deadly Ills,” unleashed a maelstrom—from both those advocating alternatives to animals in research as well as those defending animal experimentation. The article’s first paragraph described the study’s finding that “the mouse model has been totally misleading for at least three major killers—sepsis [a life-threatening systemic infection], burns and trauma. As a result, years and billions of dollars have been wasted following false leads.”

Kolata was reporting on a scientific paper, “Genomic responses in mouse models poorly mimic human inflammatory diseases,” published in the Proceedings of the National Academy of Sciences. The paper, by Junhee Seok and 38 co-authors, was based on ten years of research and funded by the National Institutes of Health (NIH). Predictably, the study and its publication met with stiff resistance within animal research circles. The study team had tried for more than a year to publish its paper, and it was rejected by both Science and Nature. One of the co-authors, Ronald Davis of Stanford University, explained to Kolata that researchers “are so ingrained in trying to cure mice that they forgot we are trying to cure humans.”

AWI scientific committee member Viktor Reinhardt described the article as “highlighting the obvious:  non-human animals are not humans.”  He added that, “When millions of animals are ‘used’ and killed every year to study human health issues, with the promise to the public that cures are just about to be found, the human patient is bearing a considerable risk. In the United States alone, well over 1 million patients are hospitalized because of serious, often deadly side effects of drugs that have been developed and tested in animals.”

On February 19, NIH director Francis Collins reiterated many points from the study and the article, blogging, “If it works in mice, so we thought, it should work in humans. But when it comes to molecules designed to target a sepsis-like condition, 150 drugs that successfully treated this condition in mice later failed in human clinical trials—a heartbreaking loss of decades of research and billions of dollars. … When the authors compared the activity of the human sepsis-trauma-burn genes with that of the equivalent mouse genes, there was very little overlap.  No wonder drugs designed for the mice failed in humans: they were, in fact, treating different conditions!”

While asserting that there are still things to be learned from mice, Director Collins went on to say, “The new study provides more reason to develop better and more sophisticated models of human disease. More than 30% of all drugs successfully tested in animals later prove toxic in human trials. The NIH plans to commit $70 million over the next five years to develop ‘tissue chips’—miniature 3-D organs made with living human cells—to help predict drug safety and efficacy. Though this is high-risk research, these chips may ultimately provide better models of human disease and biology than the use of animals.”