Toxic treasure: poisons and venoms from deadly animals could become tomorrow's miracle drugs. And few places on Earth harbor so many deadly animals as Australia's Great Barrier Reef

[Australia] has more things that will kill you than anywhere else.... This is a country where even the fluffiest of caterpillars can lay you out with a toxic nip, where seashells will not just sting you but actually sometimes gofer you.... It's a tough place.

--Bill Bryson, In a Sunburned Country

Raised, as you probably were, on film or video footage of drowsy koalas hugging eucalyptus trees, or kangaroos bouncing happily around the outback, you might wonder just what country Bryson is talking about. But consider the unassuming cone shell--just the kind of malicious mollusk that will "actually sometimes go for you."

The cone shell is a marine snail that lives in tropical regions worldwide, including the waters around northeastern Australia's Great Barrier Reef. The snail aggressively reaches out to sting prey or would-be predators, injecting toxins that are among the most powerful in the animal kingdom. Even a diminutive member of the genus Conus can carry enough venom to kill a dozen people; a single careless encounter can bring death in less than thirty minutes. What's more, the radula, a harpoonlike stinger that delivers the venom, can strike with enough speed and force to pierce a diver's wetsuit. There is almost no pain associated with a cone-shell sting, because the venom contains a strong analgesic. That's the good news. The bad news is that the toxin is a nerve agent for which there is no known antidote.

Why would anyone intentionally seek out a creature whose venom packs such a wallop? Answering that question goes a long way toward explaining why Australians, whose continent is well known for its gold and opals, have begun studying their richly varied animal populations with renewed interest. Latter-day prospectors on the continent are searching for biologically active chemicals throughout Australia's biting, stinging, venomous fauna. Those chemicals and their derivatives could turn out to be both a pharmaceutical bonanza and the foundation of a multimillion-dollar industry.

In Brisbane, for instance, laboratory workers at a six-year-old biotechnology company called Xenome Ltd have the unenviable task of "milking" cone shells. The job is not an easy one. Because the snail can bend its proboscis to sting from virtually any angle, there is no safe way to hold a live cone shell. To get the venom, the technicians dangle a small fish from forceps for the snail to sting. The snail's venom kills the fish, but it can then be safely extracted from the fish's tissue. In spite of that roundabout--and costly--procedure, Xenome's efforts have been worthwhile. The company is developing a drug based on cone-shell toxin for treating severe long-term pain. Its effects are similar to those of morphine, but because of its potency, effective doses are smaller, and so far at least, it seems not to be addictive.

Xenome's work is an outgrowth of a major bioprospecting project in Australia, initiated in 2003 by Peter Beattie, the premier of Queensland, and his government. Known as the Queensland Bioscience Precinct, the project aims to encourage the discovery of new biochemicals that might spawn major pharmaceutical products. What sets apart the Queensland bioexplorers is that they focus on molecules derived from animals, instead of from plants. At least 25 percent of the medicines currently available come from plant products, but relatively few animals so far have been assessed for medically useful chemicals. Thus, animal bioexplorers are entering largely uncharted territory, and the odds are good, they believe, that a mother lode is still out there, waiting to be discovered.

Animals, like plants, have long been known as a source of a vast array of chemicals, many of the with great potential for human use. Many frogs, for instance, secrete compounds through their skin that have powerful antibiotic proper ties, enabling them to thrive in stagnant water teeming with pathogens. Clown fish--immortalized in the 2003 movie Finding Nemo--wear a coat of slime that informs the anemones with which they live that clown fish is not on the anemone menu. Corals exude chemicals that protect them from sunburn at low tide; derivatives of those chemicals are already being marketed as sunscreens. Even compounds from sponges have led to valuable drugs: acyclovir, a treatment for herpes, and cytarabine, for a kind of leukemia.

The chief attraction of animal biomolecules, particularly the toxins, is their staggering potency: they are often hundreds of times more powerful than plant compounds that deliver a similar medicinal effect. For example, the analgesic alkaloid epibatidine, derived from South American dart-poison frogs, is about 200 times more powerful than an equal amount of morphine, derived from poppy flowers.

But why seek potency for its own sake? Why not play it safe, and simply use more of some less potent agent? After all, it goes without saying that the more powerful the toxin, the less of it is needed to achieve its effect, and so the greater the risk of an overdose.

The answer lies in the highly specific way that the most potent animal toxins attack certain kinds of cells or cellular processes. That very specificity of chemical action is often a highly prized medicinal property. It enables a drug to attack the site of a disease--a highly localized cancer, for instance--without crippling side effects. A precisely targeted drug can also act as a carrier for some other drug, bringing the second agent to the part of the body where it can do the most good. Hence, investigators reason, pharmaceuticals derived from modified but potent toxins may prove useful in targeting drug treatments.

Many animal toxins, for instance, have evolved that exploit the vulnerability of nerve cells. That makes sense--from the point of view of the attacker--partly because nerve cells, in most cases, cannot be replaced or even repaired. But nerve cells have two other liabilities that make them particularly vulnerable to even small-scale structural problems. First, they can be shut down by minor interference with any one of several critical components [see illustration on opposite page]. For example, a toxin could block neurotransmitter sites either upstream or downstream from the synapse between two nerve cells, making it impossible for a nerve impulse to travel across the synaptic gap. A toxin could bind to the neurotransmitter molecules themselves, rendering them useless. Or a toxin could block the channels that enable sodium and potassium to pass through the nerve-cell membrane, and thereby halt a neuroelectrical impulse along the length of each nerve cell. Finally, a toxin could degrade the myelin sheaths that insulate the axons of a nerve cell, causing the nerve impulses to lose strength and dissipate.

The second liability, related to the first, arises simply because part of each nerve pathway is usually made of a single strand of nerve cells in sequence, like the links in a chain. If any single nerve cell is shut down, the entire pathway is neutralized. That's why the system is so readily sabotaged by minute doses of highly target-specific animal neurotoxins. In some cone shells, for instance, the venom needed to kill those dozen adult humans would fit on the head of a pin.

Because a given toxin may target only a specific section of a particular kind of nerve cell--say, the myelin sheath of cardiac nerve cells--bioexplorers have to screen many toxins to identify which ones attack which targets. Suppose, for instance, screening leads to the identification of a toxin that attacks myelin. That toxin then becomes a key factor in a strategy for repairing some of the damage caused by myelindegenerative disorders, such as multiple sclerosis.

One way to use the toxin might be to modify or remove just its toxic part, while leaving the myelin-seeking part intact. Then, in place of the toxic part, the bioexplorer might substitute a therapeutic chemical agent, which could restore or mimic the function of myelin. Because the newly engineered drug would be so target-specific, virtually all of it could act only within the nerve cell's axonal region, making it an efficient fix in small doses. Similarly, other drugs might be designed to retard or alleviate the symptoms of diseases such as Alzheimer's and Parkinson's.