The ViroChip v3 array, developed as a collaborative project of the Ganem and DeRisi labs, contains representation of essentially all viruses present in GenBank, the genetic sequence database of the NIH. Here, the green signal shows possible positive hits, while the red signal indicates the array was correctly built.

His work with malaria got DeRisi thinking about other possible medical applications of microarrays, but it took a frustrated postdoc to launch his work on viruses. In Ganem’s lab, postdoctoral fellow David Wang, who is now an assistant professor at Washington University in St. Louis, had been studying a particular virus-replicating enzyme for 2 years and was making very little progress. Finally, Ganem suggested that Wang try something different by learning about microarrays in DeRisi’s lab. “A couple of months later,” Ganem recalls, “Dave came back to our group meeting and told us that Joe had been talking about using microarrays to detect viruses. Dave asked, ‘Do you think that’s a good idea?’ And I said, ‘It’s a great idea.’”

For Ganem, working with DeRisi was a chance to do the kind of science he likes best. After his second year of Harvard Medical School, Ganem took 2 years off to do research with viruses, and after completing medical school he did a postdoctoral fellowship in virology. Drawing on those experiences, in the early 1990s Ganem and his UCSF coworkers developed a blood test for infection with herpesvirus 8 that helped establish the virus’s responsibility for Kaposi’s sarcoma, a deadly cancer that is common in people with damaged immune systems. “That was the best moment of my professional life,” says Ganem, “when my knowledge of science and my knowledge of medicine could be used at the same time.”

Wang’s new postdoctoral fellowship in DeRisi’s lab jump-started the virus chip project. Soon they had constructed a DNA microarray designed to identify not only known viruses but also new viruses related to those already known. The microarray contained 10,000 DNA fragments drawn from every human, animal, plant, and microbial virus described in DNA databases at that time. They began testing the microarray against viruses grown in the lab, but then events in the real world intervened.

In late 2002, several hundred people in China came down with a severe form of pneumonia caused by an unknown infectious agent. Dubbed “severe acute respiratory syndrome,” or SARS, the disease soon spread to Vietnam, Hong Kong, and Canada, causing hundreds of deaths. In March 2003, DeRisi and Wang received DNA samples derived from the virus suspected of causing the disease and washed them over their microarray. Within 24 hours, they had identified the virus as a previously unidentified member of the coronavirus family, a conclusion reached at about the same time by several other groups using complementary techniques. A day later, the Centers for Disease Control and Prevention held a news conference to announce the results. In 2004, recognizing his work on both malaria and SARS, the John D. and Catherine T. MacArthur Foundation awarded DeRisi one of its half-million-dollar fellowships—part of which he has used to support malaria studies in Uganda.

Image: Courtesy of Patrick Tang/Ganem and DeRisi labs

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