One hundred years ago in a lab at Harvard University, a young zoology student was busily overseeing the breeding of pair after pair of brother and sister mice. The "Mouse Man", as he was known on campus, was trying to create the first inbred lab animal - a strain of mouse whose genes would be stable and identical.
Such a mouse would allow biologists to reliably replicate their experiments for the first time. His professor said it couldn't be done, but the Mouse Man proved him wrong. We are all indebted to those inbred mice and their descendants, which have helped researchers develop treatments for a wide range of human diseases.
IT BEGAN with one small mouse and a simple, if tedious, instruction. Clarence Cook Little was a Harvard undergraduate when his zoology professor thrust a live mouse across the lab bench and told him to learn everything he could about it. Little went one better.
In the third year of his degree, in 1909, he created the first inbred strain of mouse, providing researchers with a homogeneous genetic background on which to experiment. Before that, they could never be certain whether the results of their research were genuinely the result of an experiment or stemmed from genetic inconsistencies in their test animals.
Little, the great-grandson of America's most famous patriot, the Revolutionary Paul Revere, would remain a champion of the laboratory mouse all his life. He was particularly interested in cancer and was convinced that the key to understanding the disease lay in the study of genetics and that the best way to study genetics was by using inbred mice.
In 1929, the student who had once sketched mice in the margins of his zoology notes founded the Jackson Laboratory, a centre for research into mouse genetics, in Bar Harbor, Maine. But even he could not have foreseen the enormous power of inbred strains, says Steve Brown, director of the Mammalian Genetics Unit at MRC Harwell in Oxfordshire, UK.
"The concept of creating inbred strains is fundamental to genetic studies," says Brown.
Today, Little's original lab mouse has been joined by thousands of strains. About 25 million mice are used in labs around the world each year, making it the most common animal research model. Tiny Mus musculus has helped clarify the nature of a raft of human illnesses, from cancer and diabetes to Alzheimer's disease and obesity.
Crucially, the lab mouse has been a stand-in for humans, testing treatments which have led to the development of drugs for rheumatoid arthritis, leukaemia and osteoporosis to name but a few.
While Little is indisputably the man behind modern lab mice, he was not the first to experiment with them. Researchers of yore recognised that mice share many physiological systems with humans. They are also easy to feed and house, have a three-week gestation, produce large litters and reach maturity in just 10 weeks.
They have one other big advantage, says Karen Rader, a historian at Virginia Commonwealth University in Richmond, who has written the definitive book on lab mice, Making Mice. "The mouse is enough like us that results can apply to us, but not so much like us that people get upset about conducting experiments on them."