As victims of a frightening new chest infection gasped for breath in hospital beds around Asia, Cynthia Goldsmith was peering through an electron microscope in a government lab in Atlanta at cells being torn apart by a mysterious microbe.
The sample had been rushed to Atlanta from Bangkok, where Carlo Urbani of the World Health Organization, who sounded the first alert that a new life-threatening disease was spreading in Asia, lay dying from the illness himself.
As she studied the specimen, Goldsmith, a biologist at the U.S. Centers for Disease Control and Prevention, realized she was glimpsing germs that usually attract little attention -- viruses previously known to give people nothing worse than the common cold.
But in the midst of a global health emergency, the microbes on her slide, with the distinctive crown that gives them their name -- coronaviruses -- took on a more ominous quality.
"I was very surprised. I don't think it was on anyone's radar," Goldsmith said. "Coronaviruses are more associated with the common cold. So who would have thought it would be associated with this outbreak?"
Goldsmith's March 21 sighting was a pivotal moment in an unprecedented international public health and scientific counterattack against the first dangerous new disease to emerge in decades with the capacity to spread person-to-person -- an ailment now known as severe acute respiratory syndrome, or SARS.
As the number of afflicted persons increased to at least 2,416 cases and 89 deaths in 18 nations, including more than 130 cases in the United States, scientists were racing to confirm the link between the virus Goldsmith spotted and SARS, and to decipher its genes in the hopes of discerning its origins. At the same time, researchers were rushing to develop precise tests to identify those infected and to find drugs to kill it.
The outcome of that intense chase may determine whether the epidemic will be squelched soon or rage on.
"This is unlike any other human or animal coronavirus we have seen before," said Klaus Stohr, who coordinates the global scientific assault for the World Health Organization in Geneva. "We have learned a lot, but have a lot to learn."
The international scientific blitz has produced results in a remarkably short time. Scientists are now fairly certain SARS is caused by an entirely new coronavirus, and geneticists in labs scattered around the world are quickly decoding its entire genetic makeup. That will help them determine whether it's been hiding in nature for years, was spawned when an animal or human coronavirus mutated, or exchanged genetic material with a second virus when both infected a chicken, pig or some other animal. That's what many scientists suspect occurred somewhere in southern China last fall. It then was carried around the world by air travelers.
The pathogen transmits primarily through tiny droplets expelled by infected people when they sneeze or cough. The first symptoms, which usually show up a few days after being infected, are a sudden fever of 100.4 or above, a dry cough and other flu-like symptoms. At least 80 percent of those infected recover in about a week. But the rest get much worse, often developing pneumonia and sometimes needing a machine to help them breathe as the virus ravages their lungs. A combination of the antiviral drug ribavirin and steroids may help some of the sickest. But about 3.5 percent die, mostly the old and frail, an apparent death rate that makes it more deadly than the typical flu bug, including the devastating Spanish flu of 1918-19.
But some of the most important questions remain unanswered: Can it spread in other ways, such as through air, water or sewage? How many people who get infected get sick? How many of those who get sick recover? Are people infectious before they have symptoms? Do any existing drugs work against the virus? Does the virus get stronger or weaker as it gets passed from one person to another, and as the seasons change?
"We're in the third line of a three-act play," said Michael T. Osterholm, an infectious disease expert at the University of Minnesota. "We have a lot to go yet."
Quarantines, face masks, travel warnings and other containment efforts appear to be quashing the outbreak in Hanoi and Singapore, and the epidemic could burn out largely on its own elsewhere. But no one has discounted the possibility that "this thing could become more serious and cause more fatalities than the war that's going on in Iraq at the moment," said Robert G. Webster, an infectious disease expert at the St. Jude Children's Research Hospital in Memphis.
"If you think about the really bad organisms that have emerged in the last few years, like HIV, which is a terrible disease, the thing that saves humanity is that it's not transmitted through the respiratory system. The route that's most efficient is the respiratory route," Webster said. "That's what has everyone so concerned."
At about the same time Goldsmith and her CDC colleagues spotted a coronavirus, scientists at the University of Hong Kong were studying another high-powered microscopic snapshot of a virus found in a patient stricken by what appeared to be the same disease in that city. They saw signs of the same telltale crown.
"It has a very distinctive appearance," said Malik Peiris, a microbiology professor at the University of Hong Kong. "But sometimes appearance can be deceptive. So we went on a fishing expedition" for pieces of genetic material, which proved it was indeed a coronavirus.
"Coronaviruses have not really been recognized as agents that cause severe human disease. And this is a pretty nasty disease," Peiris said.
At the time, scientists were also focusing on other possible viruses that had been found in some patients, particularly a paramyxovirus, which causes measles, mumps and other human illnesses. Peiris's lab had been on the alert for the "bird flu" virus, which killed a father and son in early February in Hong Kong.
But when the labs in Atlanta and Hong Kong reported their findings to a new global network of 11 laboratories that WHO had assembled to fight SARS, evidence of a coronavirus was quickly found in more patients, strengthening the suspected link.
Once the probable cause was identified, scientists began to build the case against it. Tests on SARS patients from Canada, Germany, Britain, the United States and Asia usually detected antibodies to the virus; tests on most healthy people did not. More labs found the virus itself in SARS patients. The next step was to grow it in the laboratory, which was quickly accomplished by a number of labs. The final proof will be to find an animal that the virus can infect and make sick. Researchers in the Netherlands have begun trying to infect mice and monkeys.
Coronaviruses can make many creatures sick. They infect pigs, chickens, cows, dogs, cats and other animals, causing a spectrum of diseases ranging from mild respiratory infections to often deadly lung and digestive system infections. There were only two known human coronaviruses, which together cause about one-third of all colds.
The new virus is clearly none of the known viruses and may represent an entirely new class. "It's like cars. You know that cars have four wheels and seats. But some are BMWs, some are Chryslers and some are Mercedes," said WHO's Stohr. "Now we have a new one."
New viruses usually emerge in one of two ways. Either their genes are damaged during reproduction or they become mixed up with genes from another virus during reproduction, a process known as "recombination." Most new flu viruses emerge this way in southern Asia, because of the high concentration of people living close to animals.
Coronaviruses are especially prone to mutations and recombinations because they have an RNA genome, which doesn't have a "spell check" mechanism that guards against mistakes when they reproduce.
"There could have been some kind of virulence mutation. Something that was mild that became nasty. These are sloppy replicators," said Kathryn V. Holmes of the University of Colorado Health Sciences Center, one of a small group of coronavirus experts that the CDC called in to assist. "It's like evolution, where the virus is well-adapted to some niche and then a mutation occurs that allows it to get into a new one, in this case lung cells."
As the number of suspected cases increased rapidly around the world, the CDC started work on tests for the virus. That would prove crucial for determining which patients with the vague constellation of symptoms actually have SARS, how often infected people get sick, and how long they can spread the virus.
The CDC quickly produced two tests that can detect antibodies to the virus and last week announced it was starting to distribute them to state health officials. Other labs have also developed genetic tests. But none of the tests so far are reliable enough to enable scientists to get a good picture of how many people are really infected.
Left alone, coronaviruses can survive for several hours on inanimate objects, and they have been found in feces and urine. But it's unclear how often door knobs, elevator buttons, water or sewage contaminated by the virus can infect people, also a crucial question.
Scientists do know, however, that ordinary detergents and alcohol can penetrate the virus's protective shell, Holmes said. So surfaces suspected of being contaminated can be fairly easily disinfected.
The CDC has enlisted the U.S. Army Medical Research Institute of Infectious Diseases, part of the Pentagon's biological weapons program, to help develop better tests, analyze the virus's genes, and screen at least 2,000 existing antiviral drugs to see if any work against the SARS virus. The National Institutes of Health has started exploring how a vaccine may be produced, but that would be at least a year away, at best.
But none of that would be possible without having first identified the probable cause.
"This is just the first step. There are a lot more to follow," said Larry J. Anderson, who heads the lab where Goldsmith found the virus. "It's a great thing to have an opportunity to figure out if this is a new disease. But you have just a few minutes to feel good, and then you get back to work."