According to Sanjiv "Sam" Gambhir, molecular imaging is not so very different from good detective work. Just as detectives use a range of creative methods to find out what's going on behind the scenes, so do his "molecular detectives," as he calls them. They are molecules made to blend in well enough to pass through the body's passages without being noticed, while at the same time, sending back signals that reveal the secrets of the body's inner world. Gambhir, director of the School of Medicine's Program in Molecular Imaging, head of the nuclear medicine division, and professor of radiology, uses these signals to create detailed molecular images.

Molecular imaging could have a significant impact on how disease is discovered and diagnosed. For instance, Gambhir explains, "we could send in a molecular detective that could hunt down cancer much earlier than it would normally have been detected. Or we could send one into the brain and see very early Alzheimer's disease—long before there are symptoms."

Such images could also measure the effectiveness of treatments of disease. A drug's impact could be seen by imaging the places where drug molecules are gathering and working in the body. Already, pharmaceutical companies are working with Gambhir's lab to develop better drugs by using the insights that molecular imaging provides. "We're changing how we manage people and where we give therapy, because we can monitor the therapies now," he says.

This field is a relatively new arrival to the biosciences. Initially, Gambhir explains, imaging specialists who focused on X-rays and MRI (magnetic resonance imaging) technology did not communicate much with molecular biologists. But in recent years, medicine has focused increasingly on the molecular level as scientists have become interested in the genetic and molecular factors affecting disease. The multidisciplinary science of molecular imaging has since begun to flourish.

Before joining Stanford's faculty in 2003, Gambhir spent eight years building a cutting-edge lab at the Crump Institute for Molecular Imaging at University of California, Los Angeles (where he had earned his MD and PhD). He decided to make the move to Stanford—bringing 40 scientists with him—because the Clark Center and Bio-X Program offered the multidisciplinary environment he sought for his molecular imaging work. Gambhir recognizes that his field is "one of the most highly multidisciplinary," involving chemists who build the molecules, molecular pharmacologists and biologists who make the molecules function in the harsh environment of the human body, and physicists and engineers who make instruments to read their signals.

The science behind molecular imaging falls into two general categories: creating the molecules that are sent into the body and detecting the signals that they send back. The molecules used are the same as those commonly found in the body, such as carbons and oxygens, but researchers attach something special to them—for instance, a radioactive atom or a group of atoms that produces light. Gambhir's team also develops the machines used to pick up the atoms' signals and create images based on them. MicroPET (micro positron emission tomography) reads signals in animal subjects, for example, and other machines combine MRI technology with PET signal detection.

One of the research questions Gambhir is focusing on is how to detect the earliest stages of cancer. Instead of discovering a breast mass when it is several centimeters wide—the equivalent of 3 billion cells—as is typical, Gambhir hopes to spot the disease when it is a cluster of a mere few thousand cells.

Gambhir is already testing probes to detect early colorectal cancer and brain cancer in humans. His goal is to create more molecular detectives to go after human diseases. It is a costly endeavor, but one that he finds much enthusiasm for in the Clark Center. Gambhir has already found a new collaborator in Mark Schnitzer, who combines applied physics and biological sciences. Schnitzer has developed optical techniques to study neurons that Gambhir's team can apply to molecular imaging.

"There truly are a lot of interactions that are unique because of the diversity of faculty backgrounds in this building," he says. "For us, that's critical, because we need those other disciplines."