“Do you see those little white dots?” asks Anatoly Urisman, holding a conventional one-inch by three-inch glass microscope slide up to the window. With the sun shining through the slide, square arrays of tiny white dots float into view. “Those are the DNA spots.” He slips another slide into a laser scanner, and a dense grid of green and red circles appears on a computer monitor. “This one didn’t work very well,” he mutters. “Those red spots should be brighter.”

Urisman, an M.D.-Ph.D. student in DeRisi’s lab, is heading up one component of DeRisi and Ganem’s most ambitious project to date. Drawing on his clinical background, Ganem has been obtaining tissue samples from people with respiratory infections, hepatitis, meningitis, rheumatoid arthritis, multiple sclerosis, and a half dozen or so other diseases. DeRisi and his labmates then use the DNA microarray to identify viruses in the tissues. If they find suspicious viruses in patients with a particular illness, those viruses may be clues to the origins or course of the disease.

Earlier this year, the team reported the first of what it hopes will be many hits. At the Cleveland Clinic, oncologist Robert H. Silverman found a subset of prostate cancer patients with a suspicious genetic mutation. The men had a defect in a gene that produces a protein called ribonuclease L, an enzyme that defends against viral infection. With their permission, the Cleveland group isolated samples from the prostate cancer tumors of men with the genetic defect, and DeRisi’s lab washed the samples across the microarray. The tests produced a clear signal: many of the men were infected with a retrovirus, called XMRV, related to a virus known to infect mice but not humans.

The nature of the link between XMRV and prostate cancer remains unknown. It’s possible that infection with the virus is coincidental, especially since the virus is not of a type known to cause cancer in humans. Or XMRV could cause the cancer indirectly by contributing to inflammatory processes in the prostate. “In my heart of hearts, I don’t think this virus is the direct cause of prostate cancer,” says Ganem. “A hit on the array isn’t the end of a project. It’s just the beginning. If we get a connection, we still have to build a case for causation.”

Their success with XMRV has demonstrated the potential of Ganem’s and DeRisi’s approach, but their partnership is not without its challenges. For one thing, they work in different parts of San Francisco. Ganem’s lab is in the UCSF hospital overlooking Golden Gate Park and the Pacific Ocean, several miles from DeRisi’s Mission Bay lab. The two investigators and their students have become experts at navigating the hilly urban terrain that separates the two campuses.

Organizational and professional issues are more daunting than the logistics. “There are only two outcomes in this research—a home run or a strikeout,” Ganem notes. Such riskiness can be hard on graduate students and postdoctoral fellows. If a postdoc is fortunate enough to work on a project that yields a home run, everyone is happy. But a postdoc could spend a couple of years searching for a viral cause of a common disease and come up empty-handed. “I worry about that a lot,” says Ganem.

	PAGE 1 2 3 4 5 6	Go Back | Continue