Monday, Mar. 31, 2003

Tracking a Deadly Virus, Cell by Cell

By Bryan Walsh/Hong Kong

Dr. Leo Poon doesn't fish, but maybe he should think about taking up the sport. The excitable University of Hong Kong (HKU) microbiologist stands inside a cluttered lab, grasping what resembles an A4-size photo negative showing black bands streamed in vertical lines. He points to a single sliver of white on one of the bands. It's a partial genetic fingerprint of the SARS virus that is terrifying Asia—and Poon plucked it from a sea of DNA. "We went on a big fishing expedition," says Dr. Malik Peiris, the Sri Lankan leader of the HKU team that identified the probable SARS virus with help from a network of biology labs in 13 countries. "And we pulled out a big fish."

In times of medical crisis, we like to think of research scientists operating with the same mechanical precision as their sophisticated lab equipment. But that's not always the case. The HKU team pulled long hours of methodical lab work, but the speed of their discovery owed much to scientific intuition and good fortune. As Poon half-jokingly says of his own eureka moment, "It was all luck."

Fortune wasn't smiling on the team at first. Peiris and his colleagues have long been involved in the fight against the avian influenza virus, which struck Hong Kong in 1997 and again in 1999. When reports of the Guangdong atypical pneumonia outbreak began leaking across the border in late January, Peiris and his colleagues thought the disease might be caused by a mutated flu virus, like the one probably responsible for the avian flu.

But the bird theory turned out to be a wild goose chase, sending the HKU team back to their microscopes. Soon they had ruled out all of the known viruses that cause severe pneumonia. "[So] we had to take more unusual approaches," says Peiris. Finally, about three weeks ago, a set of test cells combined with nasal and throat swab specimens from pneumonia patients—the scientists assumed the mystery pathogen would be present in respiratory passages—began showing "dramatic effects." Something in each specimen was killing the test cells—proof they had found their bug.

To confirm their findings, the team took blood samples from patients with atypical pneumonia and blood samples from patients without the disease and unleashed their potential virus on them. Each blood sample with pneumonia reacted to the virus, producing antibodies that are the telltale sign of viral presence, while the control group's had no response. "It was beautiful," recalls Peiris. "That was the moment when I was confident that we actually had the virus in our hands."

Still, the killer pathogen's identity was unknown. Enter Poon and his molecular fishing rod. The 30-year-old Poon compared the DNA of normal cells with the DNA of infected cells, figured out the differences and sequenced them. It took him four days of numbing work, at 15 hours a day, until he found the one portion out of some 50 lines that bore a resemblance to a known family of viruses: the coronavirus. The probable cause of SARS had been tagged and bagged. "It was really exciting," says Poon. "You're doing it for the lab and for the whole world." The discovery of the new virus paves the way for diagnostic tests, better treatment and, someday, a possible vaccine.