Venom: Miracle Medicine?

A sea creature's poison helped cure a life of chronic pain. Could venom be the newest wonder drug?

After a freak hurricane, 14-year-old Laura McManus helped her dad clear fallen tree limbs from their yard. Tugging at a branch, she felt pain rip through her lower back. "I didn't think pain like that was possible," she says. Laura's dad rushed her to a hospital near their home in Mt. Sinai, New York. Doctors told her she suffered from stress-triggered muscle spasms, and prescribed painkillers. But the pain only grew worse. A doctor soon discovered Laura had an extra vertebra (spinal-column bone), lodged at the base of her spine. Under strain, the extra vertebra shifted and crushed nearby nerves.

For the next 10 years, pain ruled Laura's life. After five operations, surgeons implanted a pump the size of a hockey puck in her spine that constantly injected painkillers. But nothing worked. "I couldn't do anything--I had to use a cane to walk," Laura says. "I was so depressed I didn't care if I lived or died."

When she was 26, her doctor phoned one morning to tell her about an experimental new drug called SNX-111. The liquid painkiller is made from the venom, or animal poison, of a snail found off the coast; of the Philippines. "You want to give me snail poison?" Laura cried. But to her disbelief, the new medication worked almost instantly.

In their endless quest to treat chronic pain and diseases, scientists are sleuthing out unlikely sources for new medicines, including animal venom--the same poisonous substances that conjure up lethal snake and scorpion bites (see mini-poster, p. 10). "We know that animal venom acts quickly and targets very specific parts of the body--two things critical to making a successful drug," says George Miljanich, a biochemist at Elan Pharmaceuticals in Menlo Park, California, who helped develop SNX-111.

Now, in final stages of testing on volunteers like Laura McManus, the potent painkiller may well gain approval from the U.S. Food and Drug Administration (FDA). So far, the FDA has approved only a few venom-based drugs, such as captopril (KAP-tuh-pril). Produced from pit viper poison, captopril dramatically lowers high blood pressure. But dozens of these wonder drugs could be available within three to five years. "Because of their potential to make great medicines, research into animal venom has exploded," Milanich says.

TOXIC BREW

Venoms, also called zootoxins, are liquid brew of toxic chemicals that many animals--including reptiles, fish, and even bugs--use to ward off predators and seize prey. Poisonous snakes produce venom in a gland in the roof of the mouth; they inject it into prey through hollow teeth called fangs. The male platypus, one of the few venomous mammals, uses a spur connected to a venom gland on its hind ankle to stab its victims. The two-inch cone snail, whose venom helps make SNX-111, collects poison in a gland called a venom bulb. The snail shoots a tiny harpoon-like stinger at an unsuspecting fish, paralyzing its next meal. Less than one drop of this venom could kill a human within hours! Dozens of unaware shell collectors have died, mistaking this fist-sized creature for a seashell!

Whatever the animal, venom's end result is the same: It cripples a victim's nervous system, the network of nerve cells that coordinates and controls basic body functions, such as breathing and muscle movement. If your brain orders your hand to move, the nervous system transmits an electrical signal along a pathway of nerve cells from the brain to your hand (see diagram, below). Venom destroys communication between nerve cells--paralyzing your hand.

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MIRACLE POISON

So how can a deadly poison relieve human pain? Many of the nerve cells that venom targets also transmit the sensation of pain from its source--like Laura's spine--to the brain. The key was to isolate the chemical in snail poison that deadens pain but otherwise leaves the nervous system unharmed. Miljanich and his team experimented with dozens of snail-venom chemicals until they hit the jackpot: a compound known as MVIIA.

Next, researchers had to produce usable quantities of MVIIA without killing every cone snail in the Philippines. Luckily, they were able to synthesize, or copy the original venom, by duplicating its chemical structure in a laboratory. The new man-made compound, called ziconotide (zi-CONE-uh-tide), or SNX-111, targets nerve cells activated by the element calcium. In fish, these cells direct muscle movement. But in humans, the cells exist only as pain sensors concealed in the spinal cord. When a doctor injects the compound directly into Laura's spine, ziconotide blocks signals along pain-sensing nerves from her spine to her brain. But it doesn't block any other nerve signals, like those that control alertness and thinking. So Laura has no side effects.

It may be hard to believe, but venom gave Laura McManus a new life.

RELATED ARTICLE: Feeling Pain

How does your body detect pain? Say you're cooking in the kitchen and accidentally touch a scalding pot. The instant your finger touches the pot, your fingertip's nerve endings, bundles of pain-sensing cells called sensory neurons, trigger an electrical signal or impulse.

The impulse travels through nerves in your arm, up your spinal cord (a canal running through your back that contains millions of neurons) to your brain. The impulse reaches your cerebral cortex, the brain region that interprets pain impulses.

After the cerebral cortex processes the impulse, a signal shoots back down the spinal cord to motor neurons, nerve cells connected to muscle tissues. The impulse causes your arm muscles to sense pain and contract, or move. As a result, you yank your arm away from the hot pot. The process happens within one-thousandth of a second, so you probably won't even realize you touched the pot until you pull your hand away. Ouch!