Laura Lewis
for National Geographic News
May 17, 2002
Scientists have discovered a wild Australian frog stocked
with its own ammo and prepared for chemical warfare.
The frog, of the genus Pseudophryne, secretes a unique poisonous
alkaloid from its skin, which offers protection from would-be
predators.
This poisonous system of defense is not in itself surprising.
Researchers have shown that certain frogs secrete the poisons
that they obtain by eating a diet high in such poisons, which
belong to a class of compounds known as alkaloids. But the
new study represents the first documented case of a vertebrate
producing its own alkaloids—essentially manufacturing
the poisons on its own.
"You may think after 30 years of looking at frog skins
for alkaloids there wouldn't be any surprises left,"
says John W. Daly, a biochemist with the National Institutes
of Health in Bethesda, Maryland, who led the research. But
the discovery of the self-initiated poison production, he
said, "was completely unexpected."
The finding was reported in April in the Journal of Natural
Products.
During many years of research, Daly and his team previously
discovered that certain frogs from tropical forests all over
the world have skin alkaloids.
Alkaloids are complex organic compounds of nitrogen, usually
from plants, that can be very poisonous. Their various forms
include such drugs as cocaine, quinine, strychnine, morphine,
and nicotine.
The unique alkaloids of frog skin protect the amphibians
from predators and perhaps from skin infections by microbes
and fungi. Snakes, for example, often prey on frogs but spit
them out upon tasting the poison.
Jerrold Meinwald, the Goldwin Smith Professor of Chemistry
at Cornell University in Ithaca, New York, said he was pleased
to learn that frogs have evolved the ability to manufacture
inborn chemical defense. "I would have been surprised
if there weren't frogs to do the necessary chemistry that
insects do all the time. It makes perfectly good sense,"
he said.
Eventual Medical Impacts?
Daly and his colleagues first learned that Pseudophryne had
unique alkaloids in its skin when they were studying the frog
in the late 1980s. The researchers named the new class of
alkaloids "pseudophrynamines," after the frog's
genus.
The pseudophrynamines in the frogs' skin were "complex
structures with no precedent in nature." Daly assumed
that the alkaloids, like those of other alkaloids found in
frog skins, originated from the diet. Yet a set of experiments
conducted in Australia and analyzed at NIH over the past three
years proved this early assumption wrong.
The research team knew that the Australian frog also possessed
another type of alkaloid known as pumiliotoxins, which were
linked with diet. Studies of poison frogs in South America
and Madagascar showed that frogs raised in captivity did not
naturally have alkaloids in their skin, but were able to accumulate
them into skin glands when given to them in their diet.
Daly planned experiments with Ben Smith, a biologist at Adelaide
University in Australia, to analyze the skin alkaloids of
Australian frogs caught in the wild and the skin alkaloids
of other frogs of the same lineage that were raised in captivity.
"I didn't suspect that they made [pseudophrynamines]
because I hadn't found any other frog that was making an alkaloid,"
Daly said.
He thought that the frogs acquired the poison by eating a
specific insect native to Australia that contained the alkaloids,
and theorized that the Pseudophryne frogs, which are nocturnal,
must have fed on certain nocturnal insects that contained
the alkaloids.
When the researchers examined skin samples from frogs in
the wild that had eaten their usual diet, levels of pumiliotoxins
dominated and only traces of pseudophrynamines were found.
The captive frogs that had been subject to an alkaloid-free
diet, however, showed high levels of pseudophrynamines and
no pumiliotoxins.
Daly concluded that Pseudophryne made their own pseudophrynamines
but obtained pumiliotoxins in their skin by eating insects
with high concentrations of these alkaloids. If they eat a
diet heavy in pumiliotoxin alkaloids, he observed, then the
frogs do not need to make pseudophrynamine to defend themselves.
From Poisons to Pain Killers
The studies of pseudophrynamines and similar substances in
nature are of considerable interest because of their possible
applications to medicine and biomedical research, such as
in the production of heart stimulants, local anesthetics,
and pain killers.
"We know historically that so many drugs come from plant
alkaloids—morphine, codeine, caffeine, cocaine, nicotine,"
Daly said.
Meinwald believes there could be "all kinds of wonderful
roles" for skin alkaloids. "Things don't occur in
nature for no reason," he said. "If an organism
is making it, it must have value for life."
One factor that makes skin alkaloids from frogs potentially
useful for medical purposes is the presence of so-called nicotinic
receptors, which play a major role in pain perception, protection
from stroke, cognitive loss in Alzheimer's disease, and anxiety.
Properties of pseudophrynamine also show promise for chemotherapy
treatment, said Thomas Spande, a research chemist in Daly's
group at NIH. The frogs' ability to produce pseudophrynamines
and not pump them out of their bodies could be a model for
better techniques of chemotherapy, in which it's important
for cells not to purge the chemical agents, he explained.
The team has also speculated that the frog skin alkaloids
might have antibiotic activity. According to Spande, the researchers
are collaborating with a group at American University in Washington,
D.C., to investigate possible antifungal and antibacterial
prospects of pseudophrynamines.
Copyright National Geographic
Reprinted from http://news.nationalgeographic.com/news/2002/05/0517_020517_toxicfrog.html
