IT NOW seems almost certain that SARS is caused by a coronavirus. This family of viruses is known to cause serious disease in animals, and colds and intestinal infections in humans.
The steps necessary to prove that a particular pathogen causes a disease are called Koch鈥檚 postulates, after the 19th-century germ theory pioneer: you must find the agent in every victim, isolate it and grow it in culture, and then show the isolated agent causes the disease in lab animals.
Initially researchers in Germany and Canada reported seeing a paramyxovirus under the electron microscope in samples from SARS patients, while Chinese doctors blamed the bacterium Chlamydia, a common but non-contagious cause of pneumonia worldwide.
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It was the death of Carlo Urbani, the WHO doctor who first recognised SARS as a new disease in Hanoi and named it, that led to the discovery of a coronavirus. On 22 March the US Centers for Disease Control (CDC) sent fluid from Urbani鈥檚 ravaged lungs to Joe DeRisi of the University of California at San Francisco, who has a microarray containing over 1500 viral sequences. Depending on which sequences bind to any complementary ones in an unknown sample, he can identify the viruses lurking in it. Within 24 hours, DeRisi told the CDC that Urbani鈥檚 lungs contained a novel coronavirus.
Now the same coronavirus has been found in patients from at least eight different locations, according to the CDC, which is helping coordinate an unprecedented network of 11 laboratories worldwide working on SARS. Most compellingly, several SARS patients started with no antibodies to coronavirus, but antibody levels climbed steadily as they fought the infection.
And to finally satisfy Koch, Albert Osterhaus鈥檚 team at Erasmus University in Rotterdam has grown the coronavirus in culture and shown it causes a SARS-like infection in animals. But the case is not yet completely cut and dried: there are reports that the coronavirus has only been found in a fraction of patients in Hong Kong, though this may simply be due to the limitations of the tests used to look for it.
Assuming the coronavirus is to blame, where did it come from? The closest matches in DeRisi鈥檚 screen were apparently avian infectious bronchitis and bovine coronavirus. The first would seem to fit with statements by Chinese medical officials last week that the earliest cases of SARS in Guangdong were in bird handlers.
But Gus Kousoulas of Louisiana State University in Baton Rouge says longer stretches of the genetic sequence he has seen are closer to bovine coronavirus. In 2001 Kousoulas discovered, to the astonishment of vets, that a lethal cattle pneumonia called shipping fever was caused by bovine coronavirus, without the bacterial co-infection that is usual in most mammalian pneumonia. 鈥淚t is the only coronavirus we know that can cause lethal pneumonia in a large mammal,鈥� he notes.
Different coronaviruses do swap genes freely, as Michael Lai of the University of Southern California in Los Angeles discovered. But they can also make sudden jumps in their tissue and host preferences just through random mutations, he says.
In the 1980s, a few mutations turned a pig coronavirus that caused gut infections into one that caused a severe respiratory infection. So it is still not clear if the coronavirus is an animal strain that has developed a taste for human tissue, a pre-existing human virus that suddenly turned nasty, or a combination of the two.