Jacqueline Lees holds the lowly mouse in high regard. It is “beautifully developed” as a model system for cancer. Lees says that while researchers can learn much from cells in a Petri dish, they require living organisms to observe, for instance, the interplay of immune system and tumor cells, or how malignancies recruit new blood vessels to feed themselves. Because scientists now understand how to switch genes on and off to promote mutations in cells and specific cancers, Lees and other researchers can trigger the growth of malignancies in mice, to explore methodically the disease’s progression from first mutation through metastasis. They also test new cancer detection methods and potential therapies. The point, says Lees, is to “always ask if our understanding can be applied to human disease.”

Lees discusses how researchers have learned to induce both hereditary-type cancers and sporadic (non-familial) cancers, through a range of procedures, including engineering an “inducing” agent that “flips a gene into being mutant;” and creating a gene that carries a mutation and inserting it into the mouse genome. Through various manipulations, researchers have created mouse equivalents for human cancers of the colon, breast and ovaries, as well some leukemias. Lees points in particular to MIT’s success with modeling lung cancer. She presents dramatic 3-D images of lung cancer progression in a mouse over the course of several months, after scientists induce a mutation in its K-ras gene. By comparing mouse data with data on the human form of the disease, MIT researchers have strongly linked a mutation in the human K-ras gene to lung cancer.

Lees and colleague Nancy Hopkins hope to make even more rapid advances in identifying the genetic bases for cancers, using the humble zebrafish. Since it fully develops in 72 hours, lives up to five years, and is transparent to boot, the zebrafish provides the opportunity for “large scale screens for novel cancer genes.”