F  or those who dream of a future without animal testing, Jackson Laboratory, in Bar Harbor,
       Maine, may seem an unlikely place for this story to begin. Jackson is home to legions of mice, many of them genetically altered to exhibit particular traits that make them ideal research subjects. And Gary Churchill, a statistician-turned-biologist who serves as one of the laboratory’s principal investigators, spends much of his time devising experiments for the sometimes odd-looking creatures.

For example, there was a 2005 Jackson study involving a long, lean, muscular mouse— affectionately named Adonis—and a short, round mouse that looked rather like an ottoman. Wondering why only some people on a particular diet become obese, Churchill crossbred several hundred pairs of Adonises and ottomans to produce offspring with a mixed bag of body types and cholesterol profiles. He fed the offspring a buttery diet; tracked each mouse’s weight, muscle mass and bone density; and noted where on its body pockets of fat accumulated. Then he used computers to scan the mice’s genomes and scour their genetic variations in search of combinations that might act as an adiposity, or fat factor, that predisposed some animals to become obese.

The computer model then looked for causal connections and interactions among these genetic patterns and the mice’s physiological traits. Did a single genetically programmed characteristic, such as the length of a leg bone, determine muscle mass or another trait related to body weight, or were other factors involved? Was the influence of one trait on another a one-way street, or did it work in the other direction as well? The computer displayed the answers graphically, with arrows indicating all links and bolder arrows representing the strong connections. The analytical model further untangled those correlations and identified a few genes that seemed to determine which mice would become fat, independent of body type.

Could this still hypothetical adiposity factor predict obesity in mice—and perhaps someday in humans? Investigating that question is on Churchill’s agenda, and it will require more animal experiments—and a lot more mice. “You have to keep testing your model in mice,” Churchill says. “When you find a gene, you have to know its context in the body. What does a gene that helps clear cholesterol from the liver do in other organs? And what are the effects of environment and diet? You need animals to learn that.”

It’s Churchill’s approach to testing, which employs sophisticated computer models as well as animals, that could well become the norm for biomedical research in decades to come. And for those who dislike animal testing, that’s not the worst-case scenario.