Wall Street Journal - March 26, 2003
Marilyn Chase, Matt Pottinger, Betsy McKay and Vanessa Fuhrmans, Staff Reporters of The Wall Street Journal

The team, led by microbiology professor John Tam of the Chinese University of Hong Kong, said a virus was causing severe acute respiratory syndrome, or SARS.

But just days later, the virus they identified -- from the paramyxovirus family -- began to look like a red herring. By then, a new suspect had emerged at the University of Hong Kong, 10 miles away. Researchers Malik Peiris and K.Y. Yuen and their team identified another culprit, a spiky-crowned virus known as coronavirus, which has now taken center stage.

The torrid pace of the detective work targeting SARS demonstrates how far medical science has come since the early days of the AIDS epidemic. It took microbiologists years of false starts and frustrated hypotheses to identify that virus. This time, the World Health Organization's international consortium of labs blazed through mounds of data and three hypotheses to log breakthroughs in just days.

The elusive virus has sickened 487 people and killed 17 since February.

There is only a rudimentary antibody test for it so far, and no vaccine or cure in sight. But WHO's team of sleuths in 12 laboratories in eight countries has outpaced the experts confronting earlier epidemics by sharing their clues -- from test tubes, electron microscopes and genetic tests -- at the speed of an e-mail. Moreover, they have done it without wrangling over patents or profits. (See related article1.)

"I would say this is historic," says James Hughes, director of the U.S. Centers for Disease Control and Prevention's National Center for Infectious Diseases, which is a key player in the effort. "The laboratories around the world -- which at other times might be competing with each other to be first to sort this out -- are sharing all their information on a daily basis as it's developing, and that's why we're able to make as rapid progress as we have made."

Sorting through mounds of data, from classic century-old microbiology tests to the modern microarray technology holding all the known universe of viral genes on a chip, the team considered and discarded evidence against three main disease suspects before settling on a new member of the odd-looking coronavirus family, which also causes the common cold.

The first signs of the deadly medical threat came Feb. 10, as Klaus Stohr, manager of the WHO's influenza program, presided over an annual meeting to analyze disease trends and determine the makeup of next year's flu vaccine. He received a bulletin telling of an outbreak of atypical pneumonia in Guangdong Province in China.

He also received evidence that a new bird flu virus called H5N1 was attacking people. "We put one and one together and thought this was H5N1 beginning its trip around the world," he says. So the initial theory, floated that very day, was that the epidemic represented a murderous new strain of influenza.

But one and one don't always add up to two. As the first patients stricken with the new disease, quickly dubbed SARS, were hospitalized, genetic tests and analyses of their blood, sputum and other tissue failed to match any known strains of the flu. By March 14, Dr. Stohr says, "it became clear we were not dealing with influenza."

On March 16, WHO assembled a team of 12 laboratories around the world to attack the problem. Working from the epidemic's operational center in Geneva, Dr. Stohr encouraged the labs to consider a virus family called paramyxovirus. He set up a secure-password-controlled Web site and ran twice-daily conference calls so collaborators could share breaking scientific news and thrash out competing theories. The effort paid off.

In Germany, scientists studied a 32-year-old Singapore doctor who was hospitalized after landing in Frankfurt enroute home from a meeting in New York. Tests in a lab in nearby Marburg pointed to paramyxovirus. But in Atlanta CDC, scientists were skeptical. Their findings from other tests didn't implicate that virus.

It was the surprising announcement last Friday from Dr. Peiris in Hong Kong that was the breakthrough. Peering through his microscope two weeks earlier, he had observed that a virus wasn't only thriving in a lab culture, but killing cells. "In two days, it just went: Boom," he says.

Next, his team examined two sets of blood samples: one drawn from patients shortly after they became infected, and another from the same patients a couple of weeks after the disease had progressed, allowing their immune systems to mount an antibody defense. "To our excitement," Dr. Peiris says, "the first group was negative, while the second was strongly positive." That was strong evidence that virus was to blame.

But a mug shot of the culprit, taken with a high-powered electron microscope, displayed a face that looked nothing like the relatively smooth paramyxovirus. Instead, there were uniformly sized, round virus particles crowned with spikes-the telltale feature of the coronavirus.

To be sure, proponents of the paramyxovirus theory haven't abandoned their position. In Hong Kong, Dr. Tam says his candidate could still be acting alone or in concert with the coronavirus.

But Joseph DeRisi, a 33-year-old microbiologist at the University of California at San Francisco, recently invented a way to put the genetic blueprints of all animal and human viruses with sequenced genomes onto a new gene-hunting device called a microarray. Last Saturday, the CDC sent him the genetic data to test. Twenty-four hours later, he had confirmed the presence of a coronavirus.

The next day, Dr. Stohr, sounding exhausted but elated, said mounting evidence has led him to believe that "we are consolidating a new theory" focused on coronavirus. And on Monday, CDC Director Julie Gerberding publicly backed the idea.

In Geneva, Dr. Stohr stressed Tuesday that the puzzle isn't officially solved. Despite all the high-tech razzle-dazzle, scientists must still satisfy a century-old proof known as Koch's Postulates, which requires a multistep checking of the findings using virus from patients and animals.

Meanwhile, this week's triumph couldn't have occurred without a highly unusual decision by Mr. Peiris and Hong Kong University not to defend their proprietary stake in the discovery, worth a possible fortune in royalties on diagnostic tests. After the protracted patent battle over the AIDS test two decades ago, the Hong Kong team decided to donate their virus to all interested laboratories.

Write to Marilyn Chase at marilyn.chase@wsj.com, Matt Pottinger at matt.pottinger@wsj.com, Betsy McKay at betsy.mckay@wsj.com and Vanessa Fuhrmans at vanessa.fuhrmans@wsj.com

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