Virus detective 'takes on SARS'

Joseph DeRisi (B.S., biochemistry and molecular biology, Crown College, '92) uses his technology to identify the virus. © Robert Foothorap, Courtesy UCSF School of Medicine.

When you study viruses for a living, the stakes are often high. But the life-and-death nature of his work was never more clear to "virus detective" Joe DeRisi than when an unknown respiratory illness began infecting thousands of people in more than two dozen countries a year ago.

Scientists around the world were desperately trying to find out what was causing the illness—dubbed Severe Acute Respiratory Syndrome, or SARS—so they could screen and contain the epidemic.

DeRisi, an assistant professor of biochemistry and biophysics at UC San Francisco, thought his lab could play a crucial role. DeRisi and his postdoctoral researcher, David Wang, had been working for two years on a DNA chip, or microarray, designed to detect a wide range of known viruses and unknown members of existing viral families. DeRisi and Wang had also developed software and database applications to interpret the reactions that occur on the chip, establishing the critical relationship of new viruses to known ones.

As part of the Global Response Team formed to battle SARS, DeRisi asked the Centers for Disease Control in Atlanta to send him SARS virus samples. Within just 24 hours, his lab determined that the culprit was a previously unknown coronavirus—part of the family of viruses that usually causes mild disease with coldlike symptons. The finding came simultaneously with the CDC's own identification, providing valuable confirmation and moving scientists one step closer to controlling the outbreak.

"We were also able to sequence part of the virus," recalls DeRisi. "We forwarded that sequence to the CDC, which assisted in their efforts to sequence the whole genome."

Looking back, DeRisi says the pressure was intense—and inescapable—at a time when images of pedestrians in the Far East wearing surgical masks flashed regularly on TV. Nearly 800 people died from SARS. "There is a life-and-death aspect to this that adds to the whole high-tension, high-pressure environment," he said. "But it was one of the most exciting things I've ever been involved in."

DeRisi, two postdoctoral researchers, and one graduate student barely left the lab for three days during the SARS effort.

"We'd been working for two years on developing the technology to diagnose and identify a new respiratory pathogen, and then suddenly a global emergency happens and we're able to instantly apply this technology," DeRisi says. "It was very gratifying."

DeRisi's DNA chip has several advantages, including speed. "What used to take weeks now takes hours," he says. Another key advantage is that the chip can detect hundreds of different viruses. "Almost all other techniques in this field require you to know what you're looking for," DeRisi notes.

"When we made this array of viruses we decided that we had to have all viruses represented, including plant viruses, insect viruses, etc., not just human viruses," says DeRisi. As it turned out, DeRisi's lab found that SARS had genetic similarities to three coronaviruses that infect birds, cows, and people, but was not identical to any of those viruses. (Hong Kong researchers later found that the virus was nearly identical to a coronavirus affecting wild animals in one Chinese province.)

"It validated our technology as a method for rapid identification of a novel pathogen," DeRisi says. "We foresee that this can be a frontline defense against emerging diseases. We're not waiting for the next SARS."

While SARS appears contained for now, DeRisi's work on the virus drew international media coverage and his phone hasn't stopped ringing. In addition to talking to journalists, DeRisi also generously shares his research with other scientists and students.

Nowhere is this approach more important than in his research on malaria, which is caused by a single-celled organism known as a protozoan rather than a virus. A scourge of the Third World that kills millions annually, malaria has long been a focus of DeRisi's efforts, earning him the J. P. Morgan Chase Health Award in 2001 from the Tech Museum in San Jose for "Technology Benefiting Humanity."

DeRisi wrote about his research results on malaria last fall in a new online biology journal published by the Public Library of Science and freely available around the world. His research reveals genetic activity during a critical phase of the parasite's life cycle, indicating a potential vulnerability that could one day be exploited to treat the disease.

"If you're going to publish research that's important to the Third World, you'd better make it accessible to them," DeRisi says, noting that he has long favored publishing his results in journals that support free and open access, and posting information online.

"Malaria is a disease the First World does not suffer from, and therefore pays very little attention to," says DeRisi. "There's no money really to be made in malaria; therefore you do not see large pharmaceutical interests taking malaria very seriously," he notes. "The people who die from malaria don't carry credit cards."

DeRisi's efforts to disseminate knowledge go well beyond publishing. In an effort to make microarray technology more affordable—and less dominated by industry—he drew scientists from around the country to a short course on microarrays, held at UCSC and arranged through the multicampus California Institute for Quantitative Biomedical Research.

To DeRisi, it just makes scientific sense to share his results widely. "The idea is to enable as many people as possible to do this kind of science. We're trying to accelerate the rate of scientific discovery as fast as possible."

—Louise Gilmore Donahue