In 1999, a Time Magazine cover story asked "When Will We Cure Cancer?" and went on to predict the emergence in the next decade of new tools "for detecting the earliest stages of many cancers."

One of those tools -- born in 2005 and sporting a fairy-tale name -- is marching forward in a collaboration between Mayo Clinic and the University of Minnesota. The researchers are not suggesting that they foresee a cure, but they are opening a window on the genetics of cancer at the earliest stages.

"Already, we have identified almost two dozen primary brain tumors that appear to have been induced by a gene mutation that we introduced into our mouse models," said Robert Jenkins, M.D., Ph.D., of Mayo Clinic. While that is a remarkable discovery, he said, the tumors must be more fully studied to determine precise, genetically relevant information.

According to the National Brain Tumor Foundation, there are more than 120 types of brain tumors, benign and malignant. Each year 200,000 people in the United States and Canada are diagnosed with cancerous tumors. Mayo Clinic is one of the largest brain tumor centers in the world, with its neurologists and neurosurgeons caring for more than 3,000 tumor patients every year.

The collaboration began in the Minneapolis lab of David Largaespada, Ph.D., where the music of rockers Van Morrison, Neil Young and Minnesota native Paul Westerberg is often heard. If that is a soundtrack for science, the result of the research also sounds a bit like pop culture. What emerged was "Sleeping Beauty," a gene-manipulation tool developed in mice. Dr. Largaespada says he and his colleagues believed their approach, when unveiled in 2005 in two papers in the journal Nature, was potentially a big medical hit.

"This new way allows us to induce cancer in mice and find out what goes wrong in the development of each and every tumor -- what genes got altered in what way to cause a tumor," Largaespada says. "It's a way of inducing cancer in mice that gives us a genetic fingerprint for each tumor that tells us what is broken."

"That's important," he adds, "because we are finding that our technique gives us new human cancer genes, too. Many of the genes that we discover in the mouse are altered in the same version of cancer in people. It's really a cancer-gene-finding technology."

Sleeping Beauty in this case is not a princess. It is scientifically known as a transposon or jumping gene -- a segment of DNA that can change position in a single cell. "It allows us to randomly mutate the genome of cells in a mouse's body, and, when just the right mutation occurs, that triggers cancer, Largaespada explained.

The problem in 2005, though, was that Dr. Largaespada focused solely on mice but wanted to test human genes within his mouse model. He got on the phone to Rochester: "When I contacted Bob Jenkins, I had the idea that we could use this method to study the genetics of brain cancer, and he was all for that."

Jenkins -- a lover of science fiction who teamed with his wife, Dr. Susan Jenkins, to write the popular book "Life Signs -- The Biology of Star Trek" -- has been studying the genetics of human brain tumors for more than 20 years.

That initial conversation led to a grant from the Minnesota Partnership for Biotechnology and Medical Genomics to study the genetics of brain cancer. The two researchers began studying acute myeloid leukemia (AML) using Sleeping Beauty and specially bred mice. AML was chosen because it starts in bone marrow in cells that normally develop into blood cells. From there it can spread rapidly throughout the body.

In essence, the researchers engineer experimental mice through the insertion of specific genes and directed breeding. "We trigger cancer by breeding the right strains of mice together to activate the transposon, so it jumps into the right tissue," Dr. Largaespada said. "Using the right transfer genes, we can make it so the gene-jumping process happens only in the specific area we want it to: the liver, the gastrointestinal track or in the brain."

Dr. Jenkins notes that while his interest is brain cancer, the technology that is coming together is flexible and useful to study possibly any kind of cancer.

"In fact," Dr. Largaespada added, "we are using it now in the lab on other projects to study gastrointestinal track cancer, which in people is called colorectal cancer, liver cancer, prostate cancer, ovarian cancer and multiple other forms of cancer. It's an approach that can be generalized."

The approach has allowed Drs. Largaespada and Jenkins to see cancer's very early genetic changes, giving them a map of genes that may be mutated along the way. They are seeing that what goes wrong in the mouse is very similar to how human tumors develop. Tumors, depending on tissue involvement, develop at different speeds, and they've gathered preliminary data on some of the genetic changes that happen very early in prostate cancer.

Dr. Largaespada says the research, for now, is "pretty much basic research, but as we understand what genetic alterations are involved in causing tumors, we are hoping that this information will suggest ways to treat them." The big, on-going challenge for all cancer researchers, he said, is that "cancer is hundreds of different diseases."

"When you look at tumors, even under a microscope, they look identical but they are really not," Dr. Largaespada says, adding that cancer remains complex despite seemingly huge advances in science.

The Sleeping Beauty approach offers a potential screening method that will let researchers look for very early developing genetic mutations that lead to brain cancer tumors, Dr. Jenkins says. "The identification of these cancer genes, and the patterns in which the mutations occur in individual cases, will certainly guide future therapies," he said.

- Jim Barlow, March 2008