Making a better mouse model
In 1907, a Harvard undergraduate named Clarence Cook Little had a brainstorm about how to study cancer. For decades, scientists trying to understand the disease had been frustrated by two of its chief features: the many years it takes to develop and the enormous complexity of environmental and genetic circumstances in which it arises.
Little's solution was to create an inbred strain of mice — a uniform set of animals that develop tumors much faster than humans — so cancer occurrences could be linked to specific genetic backgrounds. From that one set of mice, still in use by scientists, was born the field of mouse genetics.
Today, genetically engineered mice are one of the most powerful means of cancer research, thanks in large part to the establishment of the Mouse Models of Human Cancers Consortium (MMHCC) in 1999. Funded by the National Cancer Institute, the consortium creates and makes available dozens of strains of mice whose cancer development bears a striking resemblance to humans. More than 100 laboratories worldwide —— including those of Dana-Farber's Ronald DePinho, MD, and Stanley Korsmeyer, MD —— are members of the MMHCC; DePinho is the group's co-chair.
"Today, mouse models exist for most major types of human cancer, as well as many sub-types," says DePinho, whose lab has been a prime source of their creation. "The widespread availability of such models is critical to understanding cancer's genetic and biological complexity and to generating new therapeutic agents and diagnostic techniques."
Mouse modeling has led to the discovery and validation of many new genes involved in cancer, DePinho notes, as well as the development and use of imaging systems to track cancer's growth and response to therapy. In the process, the MMHCC has become an "intellectual hub" for scientists engaged in model research.
"The consortium brings together a variety of experts who test new and existing models to ensure they faithfully reflect human disease," DePinho observes. "In addition, it has become an important forum for devising ways to overcome technical barriers, for advising other researchers, and planning the future of the field."
