WORLD'S LABS UNITE AGAINST VIRAL ENEMY
05 May 2003
Source: Washington Post, May 5, 2003
World's Labs Unite Against Viral Enemy
Scientists Scramble for SARS Treatment
By Rob Stein, Washington Post Staff Writer
Susan Zwiers, wearing scrubs, two pairs of rubber gloves and a mask, squirts tiny streams of pink liquid into crevices on a clear plastic plate every day at work. Each crevice cradles a colony of monkey kidney cells. She waits three days and checks to see which cells have been killed by the noxious new germ swimming in the fluid.
In another part of the high-security military laboratory, scientists have been monitoring three monkeys. Each had lung, heart and temperature sensors and a tiny radio transmitter implanted in its body. Technicians then dripped the SARS virus into two of the animals' lungs and injected the pathogen directly into the bloodstream of the third. The researchers want to see whether the primates will develop the monkey equivalent of the dangerous new chest infection.
The experiments, being conducted at Fort Detrick, are part of an unprecedented international scramble to unravel the mercurial SARS microbe's many secrets. The World Health Organization has organized more than a dozen laboratories in nine nations into a network that is conducting dozens of studies around the clock to probe the virus's tricks and vulnerabilities. Never have scientists worked so quickly, closely and effectively to fight a new disease.
While the epidemic of severe acute respiratory syndrome seems to be coming under control in many places, public health experts remain convinced the threat is far from over. The virus is still spreading in China, and epidemics -- especially with mysterious respiratory diseases like SARS -- are notoriously unpredictable. Scientists are hoping to capitalize on what could be a hiatus in the outbreak to gain ground on the menacing bug.
"We're at a crossroads," said Mark Salter, who is heading WHO's medical assault on SARS. "We have to establish what is going to happen with this disease. We can't guess, and the next steps have to be based on firm, scientifically validated information. The work over the next few weeks is vital in establishing our understanding of how this disease may take root, or not."
So virologists, microbiologists, epidemiologists, geneticists and other specialists in the United States, China, Europe, Japan, Singapore, Canada and elsewhere are racing to find answers to the most fundamental questions about the virus -- answers that will determine whether the virus is tamed or runs wild.
Can the contagion be spread by people who seem healthy or appear to have recovered from it? If so, for how long? Is the virus mutating into a more dangerous form? How much virus does it take to make someone sick? How long does it survive on doorknobs and other objects? Can a vaccine protect people? Can SARS be treated? How many victims die?
Over the weekend, scientists in the network reported the most comprehensive results of studies examining whether the virus can survive outside a sick person's body. The data suggest the germ may be able to linger on common objects, and in human waste, for hours and perhaps even days. The findings could explain how some people may become infected with no direct contact with an infected individual. They should also help find the best ways to sterilize contaminated areas.
"These answers will be crucial in helping us to contain and control the disease," said Klaus Stohr, WHO's top SARS scientist.
Many more studies are underway, and more answers could come as early as today. In Hong Kong, for example, scientists are conducting additional environmental experiments. They have also been testing more than 200 residents of an apartment tower where hundreds of people became mysteriously infected. Scientists hope they will be able to determine which of them, if any, are infectious, for how long and exactly how.
In Singapore, researchers are decoding the genetic makeup of additional strains of the virus, work that could help determine where the virus originated and whether it is mutating into more virulent varieties.
In southern China, teams are catching and testing pigs, birds and other animals in the hope of learning whether any of the animals are harboring a reservoir of the new virus that could ignite another outbreak.
In Hanoi and Toronto, researchers are assembling detailed reconstructions of the outbreaks in each city to try to discern any pattern that would reveal why some people become infected and others do not, and why some survive while others die.
And in the United States, the federal government has enlisted dozens of scientists who are conducting the whole spectrum of SARS research, at the Centers for Disease Control and Prevention in Atlanta, the National Institutes of Health in Bethesda, universities around the country and even the Pentagon.
At Fort Detrick, Zwiers and other scientists at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) are conducting a variety of research projects aimed at helping to develop more precise tests for SARS, a vaccine and a treatment.
The hunt for a therapy may be the most intense work, involving the screening of tens of thousands of existing drugs, experimental agents, known compounds and other chemical entities.
A month ago, Zwiers was spending her days inside a Biosafety Level 3 lab, testing chemicals to see whether they could kill the smallpox virus, the most feared of biological weapons. The three monkeys, an expensive and precious commodity in biological research, were likewise intended for smallpox experiments. Then came SARS.
The monkey experiment was designed to determine whether the animals would make a good model for testing any potential drugs that are found. By the end of last week, the monkey that had the virus injected into its bloodstream had begun running a fever and was starting to have trouble breathing. One of the other monkeys appeared to be starting to show symptoms.
Zwiers works in one of the most secure biological laboratories in the world. Before she was cleared to enter, she had to be vaccinated against a list of deadly pathogens. After changing into scrubs and walking under a sterilizing ultraviolet light, she punches a code on a keypad to gain entrance to the specially sealed and ventilated biocontainment facility.
Then she puts on an old pair of sneakers that she keeps at work and punches in a second code to get into her lab. The first thing she does is don her protective gear.
Every day for the past several weeks, Zwiers has measured out different concentrations of the various powders being screened, mixed them with a clear liquid and squirted them into wells the size of a pencil eraser on the clear plastic plate. Each well contains monkey kidney cells that are grown specially for this kind of testing.
Zwiers then opens a freezer and removes small plastic vials containing the coronavirus that causes SARS, which USAMRIID received from the CDC almost immediately after scientists there isolated it. The virus has a cloudy, reddish-pink cast because it has been grown in tissue culture.
Zwiers then moves to a biological safety cabinet, a big metal box with a glass shield in front and an opening for her hands. The box is specially ventilated to ensure none of the virus escapes into the room.
After thawing the virus, Zwiers dilutes it and pours the liquid into a larger plastic boat, from which she sucks up samples in a pipette.
"I don't really worry about it," said Zwiers, a microbiologist who lives in Rockville. "We're all very well trained and know how to work safely with very pathogenic viruses. We're all aware of what we're doing."
After depositing the virus into some of the wells, Zwiers places the tray in an incubator. Three days later, she will remove it and conduct tests to see which pits still have live cells.
"It's not very often that people get to work with newly emerging viruses. It's exciting to see something from the beginning. We're all involved in the learning process," Zwiers said.
USAMRIID is testing every licensed drug, as well as tens of thousands of other chemical compounds.
"This is a brand-new virus. So we're taking the brute-force approach and testing them all," said John Huggins, chief of the viral therapeutics branch at USAMRIID.
Although some doctors in Asia reported that the antiviral drug ribavirin appeared to help some patients, especially when combined with steroids, testing at USAMRIID found no evidence that it was potent against the virus.
By the end of last week, Zwiers and her colleagues had screened more than 40,000 compounds, including every licensed antiviral drug, as well as an additional 50 related compounds.
"We're seeing some interesting hits. There seem to be some compounds that seem to inhibit the virus," Huggins said.
Drugs known as interferons, for example, seemed to work, but it is unclear whether they are effective in doses humans could tolerate, Huggins said.
"We're certainly hoping to find something -- something that could be used to treat someone quickly," Huggins said. "There's a lot of urgency to this because we just don't know enough. Unless SARS goes away, we're going to have to keep going. And it doesn't look like SARS is going away."