Associated Press - Tuesday November 20, 2001
Daniel Q. Haney, AP Medical Editor

Their strategy: Sift through the hundreds of potential virus medicines developed by drug companies to see if any work against smallpox. Chances are good, they say, because 21 drugs have already been identified this way that can kill the virus in a test tube.

Whether any of these will pan out in people is uncertain, but clearly the treatment of viral illnesses has undergone a revolution since smallpox was eliminated more than two decades ago. At that time, no medicine could touch a virus. Now there are drugs for flu, herpes, AIDS and other viral illnesses.

Army scientists who lead the effort say they believe using drugs already on hand rather than creating medicines from scratch will identify treatments to attack this awesome killer.

Until recently, scientists paid little attention to smallpox. But fear of it falling into the hands of bioterrorists has changed that, and the government is using modern research tools to take a detailed look at the virus.

Besides searching for medicines, they are decoding smallpox's genes, creating quick tests for infection and finding new ways to check their theories in lab animals.

Most of this is overseen by the U.S. Army Medical Research Institute of Infectious Diseases at Fort Detrick, Md., and the Centers for Disease Control and Prevention in Atlanta. It is done at the CDC's high-security labs, the only place in the United States where smallpox is kept.

Smallpox is thought to have killed more people than any other infection in human history, including the Black Death in the Middle Ages. In the 20th Century alone, it took at least 500 million lives.

"We have to do the research, because the risk is so monumental," says Dr. Craig E. Smith, a bioterrorism expert at Phoebe Putney Memorial Hospital in Albany, Ga.

Despite the uniquely rampant way it spreads through the air and kills, some of the internal workings of smallpox are similar to other viruses. So scientists reason that antiviral drugs already on the market for other uses might stop smallpox, just as one antibiotic can kill many kinds of bacteria.

They discovered five years ago that a drug used for an AIDS complication could kill the smallpox virus in lab cultures. The drug, called cidofovir or Vistide, is used to treat eye infections caused by cytomegalovirus, which can afflict people with HIV -weakened immune defenses.

But the drug has a drawback: It must be given by injection, which could slow its use in an emergency. So scientists have tested other drugs, including some still in early development or that failed against their intended targets.

Dr. Peter Jahrling, who heads the Army's smallpox research, said the most potent are cidofovir and five similar compounds that can be given in pill form, along with 15 others that attack the virus in different ways. So far, all seem reasonably safe.

Other possible candidates have come to the Army's attention since Sept. 11 and the anthrax attacks. "Big pharma is banging down our doors saying they've got things to test," says Jahrling. "Maybe it's patriotism or maybe it's because they see a market."

He predicts that within five years, they will identify two drugs to treat smallpox by completely different biological means.

Jahrling hopes to begin testing cidofovir next spring on monkeys at CDC. Recently, his team proved that macaque monkeys can fall ill from human smallpox, which previously was thought only to harm people. Researchers used a strain of the virus isolated in India in 1964, the same one the Russians turned into a biological weapon.

People catch smallpox by breathing the virus, but monkeys get sick only if they get a large injected dose. The animals also die within a week, which is much faster than people succumb. However, Jahrling hopes to fine-tune the strain of virus and the infection strategy so their disease more closely mimics the human variety.

Since smallpox treatments cannot be tested in infected people, the researchers hope to use monkeys. Otherwise, testing must be done with related microbes, such as the monkey pox virus, that naturally target animals.

Researchers have also developed a 20-minute test for smallpox infection. In monkeys, the results are positive within a day of the animals' exposure.

In addition, scientists are poring over the virus's genes to understand how the strains vary. The CDC has 461 samples and is concentrating on 45.

Scientists have deciphered the genes of eight of them.

As viruses go, smallpox is a complicated one with nearly 200 genes. With the information gathered so far, scientists will know quickly if a terrorist attack involves a virus that has been genetically modified to make it even more dangerous. But they are just beginning to unravel the genes' workings.

"There are lots of secrets yet to be discovered there," says the CDC's Dr. James LeDuc.

Medical Editor Daniel Q. Haney is a special correspondent for The Associated Press.

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