By Laurie Goering
Chicago Tribune
Published: Sept. 1, 1998
QUITO, Ecuador -- Epibpedobates tricolor seems a big name
for something so small. 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
eyes.
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 may also become a
boon for mankind.
Abbott Laboratories of North Chicago has just completed
initial human trials in Europe of a new 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 two trials, in which the drug will
be tested on pain sufferers, are now being scheduled, said
Melissa Brotz, an Abbott spokeswoman.
"We'll probably try a broad brush on a few different
types of pain," she said.
Years of research into compounds from rain forest plants,
animals and insects are beginning to pay off for companies
like 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 new
drugs coming out of the world's tropical rainforests in
coming years. What is more worrying is whether the rainforest
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 rainforest 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 in the world 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 itself.
That ability is both 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 new drug.
Countries like 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 itself 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 like Ecuador, Colombia, Brazil and Peru
to begin strengthening their own drug industries to take
advantage of their own 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," he said.
"How many chemicals are out there? We have no idea,"
he said. "What we do know is that we're only scratching
the surface."
When the chemical structure of the Epibpedobates frog poison
was first 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 now a $40 billion a year worldwide industry in treating
long-term or severe pain not affected by aspirin or other
basic painkillers.
In the United States alone, 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 rainforests, where he and others believe
many other new wonder drugs lurk.
"My view is the only logical action is to conserve
as much intact for as long as possible," he said. "Otherwise
there will be nothing to study and we could be losing something
not only with economic value but with significance to every
other living thing on the planet."
