MEDICINE : For Virus Detectives, Main Search Is to Find Killer’s Hide-Out : Sophisticated technology has expanded knowledge of organisms. But budget constraints have affected field.
Behind the stainless steel doors of a nondescript Army compound in the foothills of the Catoctin Mountains here, and inside a highly secured building on the outskirts of Atlanta, detectives are stalking a killer.
They know the murderer’s identity; it’s the killer’s hide-out they’re after. The case is more of a where-is-it than a whodunit.
It is a painstaking and often frustrating search that occurs every time a newly identified, lethal virus emerges from nature to kill people.
“When you’re working with these viruses, you can’t be distracted,” said Dr. C. J. Peters, head of special pathogens at the Centers for Disease Control and Prevention in Atlanta. But after tracking viruses for more than 25 years, Peters also believes that there isn’t “anything in life more interesting.”
Today’s researchers are aided by sophisticated technology and recent advances in virology have expanded their knowledge about the workings of these baffling, often deadly, organisms.
Still, virus detectives often labor against formidable odds--including a dwindling number of experts in the field, perennial budget constraints and an American public that doesn’t always understand why their work is so important.
“My career has been focused on this: Where does a virus hang out, and why does it hang out where it does?” said Dr. George Ludwig, a microbiologist with the U.S. Army Medical Research Institute of Infectious Diseases. “But this sort of art is dying out, and it’s dying out because of lack of money.”
For virus detectives, living on the edge is part of the job. Accidents can happen, even under high security and when all recommended precautions are taken.
In Bolivia a few years ago, a pathologist was performing an autopsy on a woman who had died of Bolivian hemorrhagic fever. As he pulled aside one of the dead woman’s organs, his partner’s scalpel slipped and sliced through the pathologist’s gloved finger. He became sick within a week, and a week after that, he was dead.
In 1994, a visiting professor at Yale University accidentally inhaled live, potentially fatal Sabia virus when a test tube shattered. Within two weeks, the scientist was hospitalized with a 103-degree fever. He eventually recovered.
Although recent books and movies have sensationalized viral outbreaks, the reality is that many emerging organisms are in fact “only a plane ride away,” Peters said.
A virus is nothing more than a bit of genetic material, surrounded by a coat of proteins, whose sole purpose is to survive. To do so, it needs to make copies of itself, a process known as replication. But it can’t do it alone. It needs the machinery found in living cells.
Human cells are often destroyed when the virus tries to use them. This is what causes people to become ill or die.
But because it is not in the virus’ best interest to kill a host, many viruses can live and reproduce indefinitely without harming their host. Those viruses either are replicating constantly--making their host always infectious--or are latent and spring up intermittently.
Most researchers believe that ebola--currently the hottest viral mystery going--is one of those that lives and reproduces in a natural host that it does not kill.
Many of these newly recognized exotic viruses are believed to have existed for centuries in living creatures whose habitat is somewhere deep in nature--the rain forest, perhaps, or a cave, a riverbed, grasslands. It is only when humans encroach upon these once-pristine areas--an increasingly common practice--that trouble ensues.
The natural reservoir of ebola, for example, one of the deadliest viruses in history, has proved stubbornly elusive. Researchers don’t know where ebola lives, and they have no idea whether it is replicating itself constantly or living in a mostly latent state.
Ebola has been seen in only a few isolated clusters since 1976, when it was identified in separate outbreaks in Zaire and Sudan. Last year it was the source of a major outbreak in Kikwit, Zaire.
The outbreak went unnoticed for months until it reached the local hospital and began spreading rapidly through person-to-person contact. Quick work by an international team, organized by the World Health Organization, stopped the cycle of transmission--but not before 245 out of 318 infected people had died.
To try to discover where ebola lives when it’s not killing people, researchers began working back in time in hopes of finding the first, or “index,” case--the one that had been infected in nature.
“We asked in the community about any unusual deaths that might have occurred earlier,” said Dr. Ali Kahn, a CDC medical epidemiologist who traveled to Zaire. “Many of the villagers told us, ‘Yes, we know a family, very tragic, with a whole bunch of dead people,’ ” Kahn said.
The index case appeared to be a local charcoal worker and farmer who died in January 1995 and whose infection had killed 12 members of his family.
About 10 miles from his village, the man had farmed two parcels of land and made charcoal, burning wood in a dirt-covered pit. The environs included farmland, a stream, a swamp, a partially cleared forest and a deeper forest. He could have been infected in any of those habitats.
“We took anything that moved, flew or slithered,” said Ludwig, a member of the USAMRIID team dispatched to Kikwit.
Wearing protective suits, gloves and headgear, researchers set traps baited with rolled oats and peanut butter to catch small animals and strung nets to capture bats.
They caught, gassed and labeled tens of thousands of insects, bats, rodents, snakes and other animals. Blood and organ specimens were sent to CDC labs outside Atlanta; the insects went to USAMRIID in Maryland.
Now, in highly secured “biohazard level 4” laboratory facilities, researchers dressed in pressurized suits are methodically testing each sample. Even if the researchers find signs of the virus, there is more work to do. An animal exposed to ebola could be an intermediary, rather than the host itself.
Thus far, Kahn says, “we’ve found nothing at all.”
The charcoal worker died during the rainy season, but the researchers didn’t get to the site of the outbreak until the dry season. Scientists had planned to return to Zaire during this year’s rainy season to collect more samples, but budgetary constraints forced them to cancel.
“The ecology changes during the rainy season,” Ludwig explained. “We need to determine how all these organisms are interrelated and connected to their environments.”
This relationship can be critical. More than four decades ago, scientists identified a virus that causes an illness known as Rift Valley Fever. It was first seen in Kenya, where it began killing sheep and cattle, and then made humans ill.
Researchers suspected that it was carried by mosquitoes. But they couldn’t understand why evidence of infection appeared only occasionally, while epidemics occurred during the rainy season.
“A breakthrough came one day when a guy studying this disease mapped where all the cattle cases were coming from,” Peters said. All the hot spots matched up with locations of damboes, geological formations where water accumulates from heavy rainfall.
The mosquito under suspicion bred heavily in flood waters that collected in damboes. That connection explained why outbreaks of Rift Valley Fever occurred only during the rainy season.
Ebola is not so obvious.
Named for the river in Zaire where it was first seen, ebola belongs to a family of RNA viruses known as filoviruses. They cause hemorrhagic fever disease, an illness marked by uncontrolled internal bleeding.
There are four known subtypes of ebola: Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast and Ebola-Reston, all named for where they were found.
Researchers found samples of the Zaire strain, taken from the 1995 and 1976 outbreaks, to be remarkably similar--raising the possibility it could be latent.
Dr. Peter Jahrling, a USAMRIID scientist, believes that the circumstances known about the Reston strain, named after the Virginia town outside Washington where it was detected in 1988 among monkeys imported from the Philippines, offers some clues about how ebola is transmitted.
The Reston strain can infect humans but doesn’t sicken or kill them. It has turned up four times in the United States and once in Italy. In each case the carriers were research monkeys exported from the Philippines by the same company.
Other Philippine exporters ship monkeys caught on the same island, but ebola has not been found in any of them, Jahrling says. He thinks the monkeys are infected after they arrive at the exporter’s compound and suspects that the virus is carried in a mouse.
“The rodent density [at the compound] is incredible,” he said. “Places like that attempt to control the rodents with warfarin,” a drug that makes the rodents bleed internally and ultimately die. But before they die, they slow down--making them an easy target for the monkeys.
“The monkeys eat the drugged mice. I think there’s a real possibility that’s how they are getting infected,” Jahrling said.
