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All-Purpose Drugs Are Being Tested

By JEFF DONN, Associated Press Writer  Silver

American smart bombs zero in on programmed targets in Afghanistan. Bioterrorism protection at home may demand drugs that do just the opposite - kill just about any germ target in sight.

Some researchers are trying to fashion such universal drugs. They would combat a wide spectrum of germs, the immune system breakdown from radiation, and maybe chemical agents of terrorism, too.

One researcher, Dr. Ken Alibek, understands the need better than most. A medical doctor specializing in microbiology, he was once scientific director of the Soviet program in germ warfare.

Alibek came to oppose germ weapons after 17 years of work and emigrated to the United States in 1992. He is now president of Hadron Advanced Biosystems in Manassas, Va.

"I knew the problem of biological weapons," he said this week in strongly accented English. "There's a huge number of different agents. I knew vaccines wouldn't be a perfect approach."

Still, the quest for broad-spectrum drugs runs against the medical mainstream, which is intent on realizing German researcher Paul Ehrlich's 90-year-old dream of targeting "magic bullets" at specific microbes.

"Instead of a magic bullet, we are making a better fort," said virologist Roger M. Loria, who researches all-purpose drugs at the Medical College of Virginia in Richmond.

Scientists have explored the idea for decades. Often focusing on bolstering the immune system, they hoped to find all-in-one treatments for common ills like cancer, pneumonia or flu, or to mitigate side effects from chemotherapy or radiation treatments. Over the last several years - and especially in recent weeks - worries about terrorism have motivated the search for such drugs. However, they are mostly in early testing and wouldn't be ready for two years, at best.

While universal drug candidates vary, they tend to work in a common way: by revving up the body's broad, innate defensive shield against foreign germs or their toxins. Unlike antibiotics, most of these new drugs would not directly attack an invader. Unlike vaccines, they would not confine their attack to a narrow group of germs remembered by the immune system.

Still, skepticism has run deep among health authorities. It was only last year that Alibek landed a $3.3 million Defense Department contract to research such drugs. And last month, his company announced another grant - $800,000 from the National Institutes of Health - to focus on anthrax.

Alibek is experimenting with immune-signaling proteins known as cytokines and with peptidoglycans, bulky molecules that form the cell wall of germs and touch off immune defenses in people. Alibek says he has carried out successful early laboratory testing for anthrax and a relative of smallpox.

He is trying to deliver such drugs by inhalation to send them where they are most needed against airborne bioterrorism germs - and to limit any allergy-like side effects elsewhere in the body.

At the Virginia campus, Loria is testing androstene steroids as broad-spectrum drugs. He says these hormones appear to block the action of cortisone, the immune-braking steroid known for its ability to ease inflammation.

Loria says such steroids work in the laboratory against viruses, bacteria and parasites. A single injection enabled 70 percent of mice to survive a herpes bug that otherwise would have killed all of them, he says. He suspects the drugs might work similarly on bioterrorism germs.

Studying ways to protect soldiers, Defense Department researchers have published findings showing that such drugs also preserve the immune systems of mice exposed to radiation. It is immune system damage that often kills people exposed to heavy radiation, because it invites infections.

"If you can correct the immune damage, the patient can heal himself," said Robert Marsella, vice president of Hollis-Eden Pharmaceuticals in La Jolla, Calif. The company has acquired rights from Loria and others to develop such drugs. It has progressed to human testing against HIV, malaria, hepatitis, a skin cancer precursor and other conditions.

Jeanette Roberts, a chemist at the University of Utah's College of Pharmacy in Salt Lake City, took a different approach. She tested the power of the amino acid cysteine, a component of the liver's toxin-fighting glutathione, to help disarm a germ poison. Glutathione works by donating an electron to stabilize overactive free radicals, molecules that proliferate dangerously under toxic stress.

Cysteine is normally toxic, too, but Roberts chemically rolled it into a ring to mask its presence until needed. She said the approach might work with everything from botulism toxin to nerve gas.

Glutathione is already sold as an antioxidant dietary supplement.

Another supplement under serious academic study as an all-purpose drug is silver. It has been hawked for decades as a popular remedy for a variety of ailments, so microbiologist Ron Leavitt at Brigham Young University balked three years ago when a company first asked him to test its solution scientifically.

"I said, 'Go away!"' he recalled in an interview. "I fully expected it not to do a thing."

Reluctantly agreeing, he compared the silver compound to the common antibiotic tetracycline in action against 11 germs. In each case, he says, the silver compound worked as well or better. Leavitt says he doubted his own findings, so he did the experiments again - and again. The results were the same against those strains and nine others. One was E. coli, another potential agent of terrorism.

The interested company, American Biotech Labs of Alpine, Utah, has begun to test the solution for anthrax and ear infections, says spokesman Keith Moeller.

Leavitt says silver, at the levels used in the solution, appears to be toxic to germs but safe for people. He plans to extend his experiments to animals. He suspects the silver acts as a catalyst, perhaps promoting a reaction that short-circuits a germ's energy metabolism.

One potential drawback, he said, is the danger of killing desirable germs, like those that protect the skin and mouth against disease microbes. Immune-regulating drugs are less likely to show this disadvantage, because the immune system knows pretty well how to tell friendly forces from those of the enemy.

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