Taking a saliva sample from the world's largest bat is not easy under ordinary circumstances, but obtaining that same sample from a SARS-infected flying fox — while using a 4-foot cotton swab and wearing a pressurized biosafety suit with double-layered rubber gloves — can be downright infuriating. "There comes a point where you just have to say 'that's enough,'" says Gary Crameri, a technician at the Australian Animal Health Laboratory (AAHL) in Geelong, about an hour's drive south of Melbourne.
When I visit him in late November, Crameri had just exposed half a dozen flying foxes to the virus that causes SARS. The hope is that this tricky experiment will shed light on a molecular receptor that SARS seems to be using to get inside cells. If this hunch about receptors is correct, then knowing which bats possess the susceptible receptor could guide the ongoing hunt for the pathogen's reservoir among hundreds of bat species (including relatives of flying foxes) caught and traded by locals in southeast Asia and China. But if a glove is punctured or the air supply slips off, Crameri would have to camp out in a quarantine unit for two weeks — an event that's happened only once in the 20-year history of the lab. "You can't afford to be frustrated," he says.
Crameri's boss, China-born virologist Linfa Wang, tells me about his research over a vegetarian quiche, as the sun glistens through the double-paned windows in the AAHL cafeteria, illuminating his immaculate white tennis shoes, white pants, and a red knit polo shirt. Wang left his civilian wardrobe behind before crossing through the airlock into the secure region of the laboratory, where this laundered outfit — carefully selected by laboratory cleaning staff — sat waiting in a metal locker. In order to reach the biosafety level 4 (BSL4) labs where Crameri is working, Wang explains that he would have to pass through four more airlocks, and upon exiting he would take an additional chemical shower. But Wang is not authorized to watch his own experiments unfold.
When the World Health Organization sent its first SARS surveillance team to China in early 2003, seven out of eight representatives were field-based epidemiologists. Wang was the only bench-based worker and the only Chinese-speaking person on the team. At the time, he had no idea just how useful AAHL's generous facilities would prove. "No lab in the world could do what we're doing," says Wang, "We have the monopoly."
AAHL is the world's largest of the few BSL4 labs geared toward the animal kingdom. Its closest competitor, in Winnipeg, Canada, can accommodate four cows at once; AAHL can handle 88. In addition to keeping dangerous viruses from escaping, the lab's hypobaric corridors have also kept the 1980s safely quarantined within: The off-white halls sport a highly stylized landscape of rainbows, trees, and wildflowers, and one room still has posters from the rock group AC/DC. "Once it's in here," laments one technician over the whir of a centrifuge, "it's more or less here to stay."
Despite the facility's stopped clock, today it's concerned with a very contemporary disease. By mid-2003, SARS had killed 774 people and sickened thousands of others. Most of the victims had been infected after eating or handling farmed civets, a popular wintertime meal. But the civets were not the true host of the virus. Wang realized locals must have caught it from the other animals traded at China's wild animal markets. In early 2005, his group made two trips to China and sampled hundreds of bats (14 different species) in the wild. On the second trip, Wang says they discovered the first SARS antibodies in a bat's saliva. When they sequenced the viruses isolated from the bat samples, they found that the viruses shared 90% of their genomes with the SARS coronavirus isolated from humans ( Science, 310:676—9, 2005). "In our paper, we said it was SARS-like," Wang says.
Australia's geographic proximity to tropical Asia gives Wang a high diversity of domestic bat species to work with. The hardest part about accommodating a mammal with a six-foot wingspan was convincing the animal-care reviewers that the bats would not get too cold during the three-hour flight from Queensland to Melbourne. (Wang first had to ship a data recorder in the cargo hold in order to monitor in-flight temperatures.)
But the group has yet to identify the reservoir host of the actual SARS virus, which brings Wang back to exactly why he has asked Gary Crameri to see if SARS antibodies are showing up in bat saliva. Wang hopes that his careful studies of the cell-surface receptor can be used to predict the bat species that are more likely to be the wild host, and he's starting by comparing megabats (like the flying fox) and microbats (like the horseshoe bat) that Crameri is infecting this month. "I think we are on the cusp of another discovery," Wang says.