The National Microbiological Laboratory (NML) in Winnepeg, Canada has looked for more than 250 known causes of lung infection in samples from Canadian patients with SARS (Severe Acute Respiratory Syndrome) — the mystery, deadly lung infection spreading from South East Asia — and has so far been unable to identify a likely causative agent. Influenza virus, including that involved in the recent "bird flu" outbreak, has been ruled out by labs in Hong Kong.

"Whatever this is, it smacks of something brand new — a new cause of pneumonia," Donald Lowe, head of the Department of Microbiology at Mt Sinai Hospital, Toronto, told The Scientist. Lowe has been treating the nine Canadian SARS patients.

But it took six months to identify the Legionella pneumophila bacterium as the cause of Legionnaire's disease, the pneumonia that attacked an old soldiers' convention in Philadelphia in 1976. Could it take just as long to identify the cause of SARS?

Unlikely, Lowe thinks. "Since Legionella, the molecular world has changed dramatically — if we have any evidence of an infectious particle, we can amplify the DNA or RNA, sequence it, and therefore be able more rapidly and accurately to define an agent. Unless we are dealing with a virus which is difficult to grow."

One technique to amplify the causative agent of the disease involves innoculation of newborn mice — which are very susceptible to infection — with samples from infected patients. Cell lines are also used.

Given a sufficient amount of infective agent, the genetic material in a sample can be amplified, any foreign sequence picked out, and compared with sequence databases. Even with a new organism it should be possible to find the nearest relative, Lowe believes.

Julie Gerberding, director of the US Centers for Disease Control and Prevention (CDC), Atlanta, said at a press conference yesterday that the task had been made more difficult by the shortage of samples, but international exchanges would soon be improving the situation.

The World Health Organisation (WHO) is coordinating the efforts of 11 laboratories in 10 countries, including the NML, the UK's Public Health Laboratory Service, and CDC, in the effort to identify the agent.

CDC has "laboratories all over the center working on this round the clock," said Gerberding. Some tests are swift, some much slower, she said. "We have rapid tests that screen for families of viruses and bacteria, and cultures for common varieties of bacteria often become positive very quickly…. We are also doing immunohistochemical staining to look at the location of any potential antigens in tissue." But "Some of the viruses we are looking for either cannot be grown in culture or take very long times, sometimes weeks… When we can't actually grow the organism we often have to resort to the most sensitive DNA technologies that we have" said Gerberding, "and if there is not a dense infection sometimes we get a false negative from those tests… But we're doing it as fast as we can and we're prepared to scale up when we get more specimens."

Lowe said that his first two SARS patients had died. The first was a 65-year-old woman who had visited Hong Kong February 13–23. She died at home. The second case, and death, was her son "who was living with her, was admitted to hospital and very rapidly went into respiratory failure and died." Of the subsequent six cases, three required intensive care and two were put on ventilators, but all "are doing better — to date."

The initial clutch of Canadian cases was all from the same family, most in the same household. One woman spent just 30–45 minutes with them, and came down with the illness, and the ninth patient had simply been in the hospital emergency room at the same time as the man who died. From this, Lowe speculated that the transmission is respiratory and probably by droplets. In Hong Kong, 90% of cases have been in health care workers who came into contact with patients.

An outstanding question is where the disease originated. China recently issued a brief report on an outbreak of what may be the same disease that began in Guandong province in southern China in November, and peaked in mid-February. The Chinese report, including data on the diagnosis and management of more than 300 cases, is presently undergoing analysis at WHO.

Tommy Thompson, Secretary of the US Department of Health and Human Services, said yesterday that members of the CDC are now working with their Chinese counterparts.

The ministry of health in China has also requested support from an international team, which is being assembled by WHO.