well as another, more famous among teenagers, that’s sexually transmitted). One of the respiratory chlamydias is zoonotic, leaping from birds (notably, pet parrots) into humans. During late February, a very senior Chinese microbiologist found what looked like chlamydia in some SARS specimens and, based on his tenuous evidence—also, his august standing in the respectful milieu of Chinese science—the chlamydia hypothesis was embraced overconfidently by high health officials in Beijing. At least one other eminent Chinese researcher dissented, arguing that, if a chlamydia was the cause, SARS cases should have responded to treatment with antibiotics—which they did not. But that fellow was down in Guangdong, at the Institute for Respiratory Diseases, and Beijing didn’t want to hear him.
The laboratory scientists meanwhile explored other possibilities too, quite a list: plague, spotted fever, Legionnaires’ disease, typhus, several kinds of bacterial pneumonia, seasonal influenza, E. coli in the blood, Old and New World hantaviruses, and more. Part of what made the task difficult was that, in pursuing the SARS agent, they didn’t know whether they were looking for something familiar, something newish but closely resembling something familiar, or something entirely new.
And there was one other possible category: something familiar to veterinarians but entirely new as an infection of humans. In other words, an emerging zoonosis.
The sorts of lab methodology I’ve described earlier, involving PCR to screen for recognizable fragments of DNA or RNA, combined with molecular assays to detect antibodies or antigens, are useful only in searching for what’s familiar—or, at least, for what closely resembles something familiar. Such tests essentially give you a positive, negative, or approximated answer in response to a specific question: Is it this? Finding an entirely new pathogen is more difficult. You can’t detect a microbe by its molecular signature until you know roughly what that signature is. So the lab scientist must resort to a slightly older, less automated approach: growing the microbe in a cell culture and then looking at it through a microscope.
At the University of Hong Kong, high on the side of a peak overlooking the downtown neighborhoods, a team led by Malik Peiris took this approach to its fruitful conclusion. Peiris is an Oxford-educated microbiologist, born and raised in Sri Lanka, soft-spoken and judicious, with fine dark hair that hugs his skull roundly. He is known primarily as an influenza researcher and, having come to Hong Kong in 1995, just before the big bird-flu scare, he had reason to consider avian influenza as a leading hypothesis for what was now coming out of Guangdong. “The first thing going through our minds was that the H5N1 virus had possibly acquired the ability to transmit from human to human,” he told a reporter in 2003. But after testing their SARS samples for H5N1, as well as for a roster of the usual suspects, and finding no evidence of any, his team moved toward the idea that they were dealing with a new virus.
They focused then on trying to culture it. This meant, first of all, giving the mystery creature an environment of living cells in which it was able to replicate, until it grew abundant enough in the culture, and caused enough damage to the cells, that its presence could be seen. The living cells of the culture had to be one or another “immortalized” lineage (such as the famous HeLa cells from an unfortunate woman named Henrietta Lacks), so that they would continue replicating indefinitely until something killed them. Peiris’s team began by offering the new bug five different cell lines that had variously proven hospitable to familiar respiratory pathogens: cells from a dog’s kidney, cells from a rat’s tumor, cells from the lung of an aborted human fetus, and others. No luck. There was no sign of cell damage and therefore no evidence of viral growth. Then they tried another line, derived from kidney cells of a fetal rhesus monkey. Yes luck. By the middle of March, they could see “cytopathic effect” in their monkey-cell culture, meaning that something had begun to replicate within those cells and destroy them, spilling from one cell to another and creating a visible zone of devastation. Within a few more days, the team had electron microscope images of round viral particles, each particle encircled by a corona of knobs. This was so unexpected that one microscopist on the team had recourse to what amounted to a field guide; he browsed through a book of viral micrographs, looking for a match, as you or I might do for a