From: Tina Shelby (tshelby@usit.net)
Tue Feb 15 14:28:51 2000

>Delivered-To: chronicpain@apollo.dns-solutions.net
>Date: 14 Feb 2000 23:30:58 -0000
>From: jim@goedhart.com
>To: chronicpain@list.goedhart.com
>Sender: owner-chronicpain@list.goedhart.com
>Reply-To: chronicpain@list.goedhart.com
>QUITO, Ecuador -- Epibpedobates tricolor seems a big name for something so
>Little longer than a fingernail, the tiny frog can easily hide in the heart
>of a flowering plant, a bright jewel of red and green with shining black
>The brilliant color is a warning. The frog's skin secretes a deadly poison,
>which Ecuador's rain forest dwellers have long used to coat blowgun darts
>for hunting. When the poison enters the bloodstream of a monkey or sloth,
>the animal quickly dies.
>Soon, however, Epibpedobates tricolor also may become a boon for mankind.
>Abbott Laboratories of North Chicago has just completed initial human
>trials in Europe of a painkilling drug based on a derivative of the frog's
>poison. While the results have not yet been made public and the company is
>hesitant to talk about ABT-594, as the chemical is known, scientists say
>the drug is 200 times as powerful as morphine, lacks morphine's addictive
>problems, and might one day take that drug's place as the world's leading
>treatment for intense and chronic pain.
>"Abbott, I think, was very lucky to be able to separate the toxicity from
>the desired analgesic effect," said John Daley, a scientist at the National
>Institutes of Health who initially identified the chemical structure of the
>frog poison.
>With many drugs derived from natural substances, such as digitalis used in
>the treatment of heart problems, "nobody's been able to get rid of the
>toxicity. That's usually the problem," he said.
>ABT-594, however, has passed its initial human trials, which determine
>whether the drug produces problem side effects in healthy users. Phase II
>trials, in which the drug will be tested on pain sufferers, are being
>scheduled, said Melissa Brotz, an Abbott spokeswoman.
>"We'll probably try a broad brush on a few different types of pain," she
>Years of research into compounds from rain forest plants, animals and
>insects are beginning to pay off for companies such as Abbott, which
>synthesized up to 500 variations of the Epibpedobates frog poison before
>deciding to go forward with ABT-594.
>Scientists say they expect to see a growing number of drugs coming out of
>the world's tropical rain forests. What is more worrying is whether the
>rain forest and its animals will still be there to provide their
>potentially miraculous compounds in the future.
>The tiny frog that gave birth to Abbott's new painkiller is endemic to
>lowland rain forest slopes in southwestern Ecuador, near the town of Loja.
>Today, less than 6 percent of the frog's original habitat remains intact.
>When Daley first came to Ecuador in the late 1970s to collect samples of
>the frog, he was able to take home more than 750. Within a few years, road
>building and human settlement put the frog on Ecuador's threatened species
>list and further collecting was outlawed.
>"Human competition is their worst problem," said Maria Elena Baragan,
>director of Quito's vivarium, which displays a collection of the tiny
>poison dart frogs.
>Today, the frog has managed somewhat of a comeback by adapting to life in
>Ecuador's coastal banana plantations, where it is commonly found. The
>problem is that in its altered habitat or in captivity the frog no longer
>produces its poison.
>Scientists have not yet determined what it is about the frog's forest
>habitat that allows it to produce the vital chemical. "There just are no
>studies," Baragan says. But work on some of the other 100 or so species of
>poison dart frogs suggests it is probably some ant, millipede or beetle in
>the frog's diet.
>"The frog without its intact surroundings is useless," said Roderick Mast,
>a vice president and frog expert at Washington-based Conservation
>International. "It's a wonderful conservation flagship species. You have to
>conserve its entire habitat to conserve it."
>Whether the frog and its habitats will be protected, however, remains in
>question, in part because Abbott's new drug, a variation of the natural
>frog poison, can be synthesized in the laboratory without the frog.
>That ability is a blessing for native frog populations that might otherwise
>be decimated by collecting for medical purposes and a curse in that their
>protection is no longer key to development of the drug.
>Countries such as Ecuador, which are only now working on laws to claim
>intellectual property rights on the genetic variety in their forests,
>generally get no share in the profits of new drugs produced from their
>plants or animals.
>Other countries have passed laws that patent the genetic material but not
>derivatives of it, the case with ABT-594.
>That has left many South American countries with little money for or direct
>interest in promoting conservation of their rain forest species.
>Mast calls that shortsighted and says part of the answer is for countries
>such as Ecuador, Colombia, Brazil and Peru to begin strengthening their
>drug industries to take advantage of their resources.
>"Our basic understanding of biodiversity is pathetic," he said. "We barely
>know what species are out there let alone the alkaloids they have in their
>skin or what they might be good for.
>"How many chemicals are out there? We have no idea. What we do know is that
>we're only scratching the surface."
>When the chemical structure of the Epibpedobates frog poison was determined
>in 1990, Daley found that the chemical worked as a powerful painkiller but
>not through the same opioid receptors targeted by morphine.
>Abbott's non-toxic derivative focuses instead on nicotine receptors,
>raising the possibility that other kinds of addiction might be a problem.
>So far, however, the company has reported no addiction problems and early
>testing in rats showed animals taken off the painkiller suffered no lack of
>appetite, a normal withdrawal sign.
>The drug also appears to make users alert, rather than sedating them, as is
>the case with morphine.
>"Abbott got the jump on everyone else on this because they have been
>working on nicotine derivatives forever," Mast said. "They weren't
>particularly looking for painkillers but as a good chemical company they're
>always on the lookout. This popped up as something with potential."
>If the drug eventually wins U.S. approval from the Food and Drug
>Administration, a process Abbott says is still years away, it could
>potentially snare a major share of what is a $40 billion a year worldwide
>industry in treating long-term or severe pain not affected by aspirin or
>other basic painkillers.
>In the U.S., the company estimates 30 million to 40 million people suffer
>pain that might be treated by ABT-594.
>Mast calls the promising new drug reason enough to step up conservation of
>rain forests, where he and others believe many other new wonder drugs lurk.

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