Sunday, December 7, 2008

Virus hunter looks to make more medical breakthroughs at UCSF

Joe DeRisi and his "ViroChip" will be vital components of a new center for viral diagnosis and discovery at UC San Francisco.

Joe DeRisi sometimes pays a peculiar price for fame.

The man who invented the virus-seeking "ViroChip," who helped identify the cause of SARS and who won a MacArthur "genius" award in pursuit of the secrets of infection has become a magnet for medical mysteries.

Every month or so, someone gets past security, up the gleaming stairways of UC San Francisco's Genetech Hall, and into DeRisi's lab with the same distraught demand: Test me.

DeRisi gently sends them away. He runs a research lab, not a clinic.

It has been harder, however, for DeRisi to sift through the barrage of fascinating calls and e-mails from doctors, veterinarians, hospitals and other researchers.

"We get requests for (testing) cancers all the time … any type of cancer you could imagine" that might be caused by a virus, DeRisi said. "It's been a little disappointing that we haven't been able to do more."

That could change early next year, when UCSF launches a center for viral diagnosis and discovery. Its ambition is to hunt down more causes of pneumonia, encephalitis and other lethal and disabling conditions whose origins too often baffle doctors, even as their patients are slipping away.

"Our plan is: Make it open to everybody," from doctors with a single troubling case to large research efforts such as the state-run California Enchephalitis Project, said Dr. Charles Chiu, an infectious disease specialist who'll head the center.

DeRisi will be an adviser, and his ViroChip, a microarray that holds genetic snippets of thousands of viruses on one glass slide, will be one of the key sleuthing tools.

The center is just the latest spinoff of a passion for pathogens that has taken DeRisi from a childhood in Carmichael to scientific renown.

"I'm really interested in pathogens that make other things ill," he said. "This ongoing battle between host and invader … including different countermeasures, counter-countermeasures, evasive tactics, stealth systems. It's amazing."

He was speaking last week in an office cluttered with stacks of scientific journals, a tangle of computers and a martial arts punching bag.

The conversation ricocheted from calligraphy to computer programming, from Del Campo High School – "a great public school education" – to his childhood paper route – "a rip-off job."

Those were only detours from his career's two main research tracks: malaria and the army of viruses that attack people, parrots or bees.

"Joe has a very high-energy personality. This guy is on 30,000 volts all the time," said Dr. Don Ganem, a UCSF professor of medicine and microbiology who has collaborated with DeRisi on several virus hunts.

"He's a phenomenal intellect …" Ganem said, "in a league with only a few other people in the world, many of whom have already won the Nobel Prize."

Oh, and DeRisi is not yet 40.

Slight and curly-haired, DeRisi has a cell phone packed with photos of his 5-month-old and 3-year-old daughters and fond memories of the tandem mountain bike he and his wife have mostly abandoned in favor of parenthood.

He grew up water-skiing on Folsom Lake, dabbling in school science experiments, commercial art and computers. In the sixth grade, he started to program, for fun.

He fled the Sacramento Valley heat to attend UC Santa Cruz and Stanford, where he immersed himself in jujitsu and biochemistry and began his fascination with malaria.

"It is not a disease of the first world," DeRisi said of the mosquito-borne parasite estimated to kill 1 million or more people each year. "It is not a disease in which there's large corporate interests. There's no profit to be made. … It wasn't really getting the kind of attention that it deserved."

As a doctoral student, he'd been working on tracking activity of thousands of genes at a time. He later trained that tool on malaria, publishing a landmark analysis of its genetic activity during its proliferation in the human bloodstream.

Since then, DeRisi has collaborated with others looking for weak links in the parasite's basic biology, anything that a new drug might be able to attack or exploit. If one potential treatment lives up to its early promise, it could be a couple of years away from testing in humans.

While immersed in malaria, DeRisi also has written software, built robots and created devices that have made possible broader virus testing, including his 2003 detection of the virus responsible for severe acute respiratory syndrome, or SARS. Often, he posts methods and findings on his Web site or publishes in open-access journals that don't demand costly subscription fees.

"He's incredibly generous," said Chiu, "a very big fan of open-source publishing, making scientific data available to researchers everywhere."

Chiu hopes the same spirit of openness will be a key part of the viral discovery and diagnosis center that will rely on DeRisi's ViroChip, and other detective techniques, to hunt new causes of age-old ills.

"About 20 to 30 percent of the time we can't make a diagnosis in pneumonia," said Chiu. "The situation is even worse for other severe diseases like encephalitis," an inflammation of the brain whose cause is unknown in more than 60 percent of cases.

Those mysteries are "unbelievably frustrating to the family, the patients … the physicians," said Dr. Carol Glaser, who is involved in a government-funded effort to detect more causes of encephalitis.

"If you don't know what causes it, how can you figure out how to treat it or prevent it?" she said.

Eliminating a wide range of possible causes can protect a desperately ill person from undergoing risky diagnostic tests or taking unneeded drugs.

Once the new center is up and running, perhaps in February or March, Chiu expects to hear from more doctors struggling to understand unusual cases, the ones where patients keeps getting sicker and all the standard diagnostic tests come back negative.

Still, said DeRisi, "We don't want members of the public sending us weird stuff. We want them to go to their doctor and have the doctor send us stuff. "

Call The Bee's Carrie Peyton Dahlberg, (916) 321-1086.