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At Fort Detrick, a race to treat SARS
Skilled in deadly agents, Army experts test drugs to control the new virus
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By Erika Niedowski
Sun Staff
Originally published April 27, 2003



FREDERICK -- A few weeks ago their world was all bioterror. They were fighting smallpox and other infectious diseases that could threaten U.S. troops.

Today, the Army's top scientists may also be the best hope in the fight against an enemy that no one expected -- the deadly virus responsible for SARS.

"When the fire bell rings, you go down the pole. It's the right thing. It's a clear public health emergency," says Peter B. Jahrling, principal scientific adviser at the U.S. Army Medical Research Institute for Infectious Diseases.

In sealed labs in nondescript buildings, scientists on the grounds of Fort Detrick are used to handling the most dangerous agents. They routinely work with the Ebola virus wearing full-body biohazard suits. Two years ago, they opened an anthrax-laced letter mailed to a U.S. senator and conducted sophisticated tests on the powder inside.

Now, researchers at this heavily guarded base near the Catoctin Mountains are testing more than 2,000 drugs that might be effective against severe acute respiratory syndrome. The aggressive virus has sickened more than 4,600 people and killed at least 276 worldwide since November.

On Friday, the Fort Detrick scientists infected three monkeys with the SARS virus in hopes that it will help them learn more about how it attacks the body.

Normally, they study the potential threat to U.S. troops from disease and biowarfare. Jahrling said it was a "hard sell" to convince some of them a few weeks ago how important it was to shift gears, particularly in the middle of the war in Iraq.

"It's a bit of a balancing act," he said. "We are probably the best-equipped lab to get these answers in short order."

Scientists here have screened about 125 compounds since receiving a plastic foam box containing samples of the SARS virus from the Centers for Disease Control and Prevention last month.

"We're not trying to be too clever, because we don't know enough about the virus to be too clever," said John W. Huggins, chief of viral therapeutics in the institute's virology division and head of the 20-member SARS team.

Already, they have determined that one leading drug, ribavirin, used in combination with steroids on SARS patients in Toronto and Hong Kong, is not effective.

The only drug that has stopped the new coronavirus from replicating is interferon. But scientists fear that the dose required is too toxic to be safe.

Screening 800 drugs

In all, Fort Detrick will be screening more than 800 drugs on the market, including 40 anti-virals used to treat AIDS, herpes, hepatitis and influenza. Finding an effective treatment among that group would be the best-case scenario because the drug could be used immediately.

But none seems promising so far.

Scientists are planning to test at least another 1,500 drugs that are under development in laboratories.

The National Institute of Allergy and Infectious Diseases in Bethesda has been gathering them, primarily from pharmaceutical companies, and sending them to Fort Detrick.

Huggins believes that at best, researchers will find an existing drug that "sort of works." But in the end, he says, it may be necessary to develop an altogether new one.

At least one drug firm, AVI BioPharma of Portland, Ore., has been collaborating with outside labs to do just that. The company, which has worked with animal coronaviruses in the past, plans to send its new compound to the National Institutes of Health for further testing, a spokeswoman said.

Viruses are harder to defeat than bacteria, in part because they frequently mutate. The new virus believed to be behind the SARS outbreak consists of a single strand of RNA, which can make mistakes as it replicates.

"RNA viruses are, by their nature, very easily mutated," Jahrling explained.

Another culprit?

They may also recombine with other viruses. Jahrling thinks that scientists world-wide have been too quick to discount the possibility of a co-infection -- the coronavirus operating in concert with another agent.

Early on in the outbreak, researchers isolated a paramyxovirus in some specimens, but the focus has shifted almost exclusively to the coronavirus.

"Coronavirus is clearly a factor in this, and it may be just as simple as it appeared," Jahrling said.

"But maybe not."

Scientists in Canada have found the coronavirus in only 40 percent of the samples taken from probable SARS patients.

Dr. Frank Plummer, scientific director of Canada's National Microbiology Laboratory in Winnipeg, Manitoba, conceded that researchers could be looking in the wrong place -- in specimens taken from the nasal passage.

They could also be overdiagnosing SARS patients, meaning that those suspected of having the disease actually have another respiratory illness.

Even so, Plummer said last week that the link between SARS and the coronavirus is not yet clear.

'A fuzzy target'

If researchers do find an effective treatment, the virus could learn to outsmart it.

One strain of tuberculosis, dubbed multiple drug-resistant TB, can no longer be killed by traditional TB drugs, making it much more dangerous.

"It's a fuzzy target," said Jahrling, a top government virologist and one of the few scientists who have worked with smallpox in recent years.

But, he added, "It's infinitely better to have something than nothing. You use it until you find it's ineffective."

Scientists at Fort Detrick hope they will learn more about the virus from the animal experiment launched Friday.

Wearing battery-powered respirators and impermeable Tyvek suits in a "Biosafety Level 3" lab -- the second-highest level of danger -- they infected two sedated monkeys by dropping virus particles into their noses and sticking a bronchoscope into their lungs.

The third monkey was infected intravenously.

The monkeys, who could become ill within several days, have chest implants that will allow researchers to monitor their heart rate, blood pressure temperature and other signs. Chest X-rays will be taken every other day, along with measurements of blood oxygen levels.

The goal, in part, is to learn more about the way the virus works.

If any of the monkeys die, re-

searchers want to figure out whether it was simply because the virus attacked and shut down tissue cells or because their bodies launched an overzealous effort to fight it off.

They may also use infected monkeys in the future to test promising drugs or vaccines

Jahrling, for one, thinks SARS is here to stay -- much like the flu. "I'm moderately optimistic that we'll find something that has some efficacy" against it, he said.

But that doesn't mean it will be ready or appropriate for use in patients soon.

"That's going to be more of a challenge," he said.