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On April 29, 1997, the supermarket tabloid the National Examiner ran this headline on its cover: “Miracle Pain Cure: Deadly Snail Venom.” The garbled story within contained a kernel of truth. Doctors in fact were injecting a drug derived from the venom of a marine snail into patients suffering from the worst kinds of pain imaginable.

One of the researchers responsible for this unlikely drug, neuroscientist George Miljanich, sits beneath a framed copy of the tabloid cover, which shares wall space above his South San Francisco, CA, desk with more staid covers from the journals Molecular and Cellular Neuroscience and the Journal of Neurocytology, among others. Miljanich works for Dublin, Ireland-based Elan Pharmaceuticals, and his snail-derived drug is called ziconotide.

For the last 50 million years, predatory snails in the Pacific Ocean have been stabbing passing fish and killing them with their venom. In tiny amounts, though, one component of the venom actually blocks the pain in desperately sick and injured people-at least among the nearly 2,000 who have tried it to date. “Ziconotide is about a thousand times more potent than morphine,” Miljanich says. “Upwards of a third of these patients experience significant improvement in their quality of life.”

Ziconotide is not yet approved by the U.S. Food and Drug Administration, and because it can cause severe side effects, its future remains uncertain. But its ultimate fate in the marketplace is, in a way, beside the point. Because of its effectiveness in halting pain, ziconotide has spawned a new generation of drugs deliberately designed to block the electrical impulses that generate pain signals, without affecting other systems in the human body.

These efforts represent an entirely new way to treat pain, one with such commercial promise that at least a dozen companies-from small biotech companies to pharmaceutical powerhouses such as GlaxoSmithKline and Merck-are investing billions of dollars in an effort to improve on nature by creating synthetic molecules more potent and safer than ziconotide. Human trials of some of the drugs could begin within the year. “The idea here would be a drug that only takes out the pain,” says neuroscientist Allan Basbaum of the University of California, San Francisco. “And that’s on the horizon.”

The need is pressing. According to the American Pain Foundation, more than 50 million Americans suffer persistent pain. Morphine, first chemically isolated from the poppy plant 200 years ago, remains the drug of choice for severe pain. Despite its many side effects, including drowsiness, interference with breathing, constipation, and the potential for addiction, “no one has bettered it,” says University of Michigan pharmacologist John Traynor.

Many “new” painkillers are in fact anything but, and they have problems similar to morphine’s. OxyContin, for instance, is actually a morphine derivative that has been in use since 1917. The difficulty with all of these older drugs is that they act throughout the nervous system, not just on pain-sensing nerves-hence their side effects.

A few more-selective new drugs do exist, including the cox-2 inhibitors used to treat arthritis pain (Merck’s Vioxx or Pfizer’s Celebrex, for example), but for really severe pain, they might as well be sugar pills. People with postsurgical pain, intense cancer pain, traumatic injuries, and severe chronic back pain must often still resort to morphine and its narcotic cousins for relief. And sometimes, even morphine is not enough.

Seven years ago, Vicki Wiltshire was rear-ended while driving to a physical-therapy appointment; the collision aggravated a back injury she had suffered earlier and sent her into a spiral of pain and despair. Four surgeries later, the former realtor has screws and rods in her spine, three fused discs, and masses of scar tissue. She cannot bend or twist without excruciating pain.

Suicide, at times, has crossed Wiltshire’s mind. “We don’t have guns in the house,” she says. “You cannot live in that kind of pain day in and day out.” Such chronic pain is not a dull throbbing. “Your body is screaming constantly,” says Elaine Casanova, a former secretary who wrecked her back in a small-plane crash. “Think about having a toothache for 10 years.”

Both Wiltshire and Casanova have taken morphine and other narcotics for long periods. Narcotics dampen but do not douse the pain, and Casanova became addicted, adding another layer of misery to her life. Both women are now on ziconotide, which they say has provided a kind of breathing space in their suffocating world of pain.

It is just those kinds of anecdotes, backed by growing insights into the neuroscience behind pain, that are finally offering realistic hope for new drugs that attack pain without producing debilitating side effects.

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