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Medicine's Wild Kingdom

One creature you don't want to stumble upon in a dark forest is a hungry vampire bat. The three-inch-long, pointy-eared night stalker has an anti-clotting substance in its saliva that allows it to dine on an unending flow of its victim's blood. There is, however, one group of people that may come to see vampire bats as lifesavers. They're stroke patients who desperately need improved clotbusting drugs that prevent brain damage and paralysis by restoring blood flow to stroke-ravaged tissues.

That's the idea behind a new drug that 15 U.S. hospitals will soon begin testing. It's a synthetic copy of an enzyme bats secrete when they salivate over freshly bitten prey. Stroke experts are already buzzing because early studies in mice suggest patients may be able to safely receive the faux bat spit up to nine hours after they've had a stroke. The only clotbusting drug now on the market must be given within three hours. "This could be a very important advance," says Dr. Anthony Furlan, section head of stroke and neurologic intensive care at the Cleveland Clinic Foundation, one of the test sites.

Bats aren't the only scary animals that may someday contribute to the world's expanding medicine cabinet. Scientists are studying everything from Gila monsters to scorpions to copperhead snakes. The toxins these creatures use to kill their prey or ward off foes--or at least traumatize unsuspecting hikers--hold seemingly boundless potential to treat human diseases ranging from diabetes to brain cancer. Refined through millions of years of evolution, the substances found in animal saliva, venom, skin, and some internal organs home in on targets such as nerve cells better than most chemical combinations scientists concoct. And often they circulate in the body for hours on end.

Still, turning Mother Nature's toxins into lifesaving drugs can be harder than killing a python with a pebble. First, researchers must isolate, analyze, and synthesize specific compounds in such a way that they can be tolerated by humans and mass-produced. The risk of failure is so high that many pharmaceutical companies shun poison-derived experimental drugs until they're well past the development stage. That leaves scientists dependent upon scarce venture capital and public funding.

Scientists are also racing against a biological clock. Species identified to date may represent just one-tenth of the biological diversity on earth. And potentially therapeutic creatures are vanishing at unprecedented rates. Although the vampire bat is not endangered, 13 other bat species are. "The natural world is the largest pharmaceutical factory we have," says Thomas E. Lovejoy, president of the H. John Heinz III Center for Science, Economics & the Environment in Washington, D.C. "A lot of potential benefit is being lost."

Witness the wonders of vampire-bat spit. German biotech company Paion is developing the drug, a genetically engineered copy of an enzyme in the bat's saliva, which it licensed from Schering. The substance zooms straight to a blood clot and breaks it down. Early studies have shown that the bat spit stays in the body longer than today's clotbusters do, and it seems to do a better job of targeting just the clot and nothing else, which may cut the risk of hemorrhaging.

Drugs like this can earn attractive returns. An anticoagulant derived from leech saliva pulled in an estimated $38 million last year for The Medicines Co. (MDCO) of Parsippany, N.J. And Capoten, a hypertension drug derived from the venom of the South American viper, drew more than $1 billion in annual sales for Bristol-Myers Squibb (BMY), before the compound went generic in the mid-1990s.

Many animal poisons have the ability to hit specific bull's-eyes in the body. The conus sea snail, for example, injects its prey with a poison that paralyzes nerve cells. And the tiny Ecuadorian poison-dart frog secretes a skin toxin that keeps predators at bay. Both substances blocks pain signals to the brain and have led to experimental pain medications that could be as potent as morphine but with no risk of addiction.

For sheer horror, nothing matches the sting of the 8-inch giant yellow Israeli scorpion. It packs neurotoxins that can cause excruciating pain. Yet at least one of the hundreds of proteins involved in that process also has the ability to seek out and bind to a receptor that is abnormally expressed on the surface of brain-tumor cells--but not on normal brain cells.

Last year, two cancer centers began testing a copy of the protein that was developed at TransMolecular Inc. in Birmingham, Ala. The researchers paired the synthesized protein with a radioactive isotope and injected it into the brains of clinical-trial patients suffering from a cancer called glioma. In the brain, they believe, the drug travels straight to tumors and kills them without damaging nearby healthy cells. "It's like a guided missile," says TransMolecular CEO Matthew A. Gonda.

Exotic animals--and their secretions--don't necessarily have to be lethal to help humans. Next year, San Diego-based Amylin Pharmaceuticals Inc. (AMLN) hopes to seek Food & Drug Administration approval for a diabetes drug derived from a hormone that Gila monsters secrete while munching on mice, bird eggs, and other favorite foods. The substance mimics the human hormone that regulates insulin, which in turn controls blood sugar. But unlike the human molecule, which is quickly degraded by enzymes in the body, the lizard version sticks around for hours. And it helps the body regenerate insulin-making cells. "This takes us to new levels of blood-sugar control," says Dr. John B. Buse, director of the diabetes care center at the University of North Carolina School of Medicine, Chapel Hill, where Amylin's drug has been tested.

Despite the promise of animal-based drugs, the path from the rain forest to the FDA is rough with pitfalls. For many companies, the biggest challenge has been figuring out how to develop and produce chemical copies of naturally occurring substances. "We don't want to be milking snakes," says Francis S. Markland, professor of biochemistry and molecular biology at the University of Southern California Keck School of Medicine, who has been developing a cancer drug based on the venom of the southern copperhead snake. With a shoestring budget from public grants, Markland managed to coax mammalian cells to make copies of the venom protein. But it will be at least a year before a drug is ready for human testing.

Emerging technologies should help speed the discovery and development of exotic drugs. Computerized screening systems, for example, allow researchers to test experimental compounds against thousands of potential disease targets simultaneously. That's important because science has barely scratched the surface of nature's therapeutic potential. "There are 10 million organisms out there waging chemical warfare against each other," says Peter H. Raven, professor of botany at Washington University. "The abundance of possible drugs cannot even be imagined."

Problem is, many of those potential remedies are disappearing before they're even spotted. Half of the world's plants and animals live in tropical forests, and most of those species are still unknown, Raven says. At the current rate of forest destruction, two-thirds of land-dwelling plant and animal species will be extinct by the end of this century.

The urgency of preserving nature's bounty isn't lost on patients like Duane Rualo. The 24-year-old accounting student at California State University at Long Beach was diagnosed with glioma in late 2001 and told he probably would not live long enough to make it to his fall 2003 graduation. After surgery and seven shots of scorpion venom, his latest brain scan came up clear of cancer. His doctors can't say yet how important the scorpion has been to his recovery. But these days, Rualo pauses when he comes across a scorpion exhibit at a zoo. "I stop and think: `Wow, they may have saved my life,"' he says. And who knows what other lifesaving drugs may be lurking beyond the scorpion's lair, the Gila monster's burrow, and the bat's cave? By Arlene Weintraub in Los Angeles, with Kerry Capell in London and Michael Arndt in Chicago

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