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From the plant-choked jungles of Malaysia to
the coral reefs of the Caribbean, scientists are combing the
planet for cures to our most intractable maladies. Such bioprospecting
is tedious work — on average only one in thousands of
natural compounds tested shows pharmaceutical promise, and
only a handful of those ever make it to market. Yet despite
the high risk of failure, researchers press on, driven by
the realization that with millions of years of experience
under her belt, Nature is the ultimate chemist.
Indeed, nearly half of all
human pharmaceuticals now in use were originally derived from
natural sources. Perhaps the most famous example is aspirin,
which evolved from a compound found in the bark and leaves
of the willow tree and was later marketed by Bayer starting
in 1899. Some 50 years later, scientists identified anticancer
compounds in the rosy periwinkle (above), which pharmaceutical
heavyweight Eli Lilly subsequently produced for the treatment
of leukemia and Hodgkin‚s disease. Other well-known
examples include the cancer-fighting Taxol, isolated from
the Pacific yew tree, and Aggrastat, an anticoagulant based
on the venom of the saw-scaled viper from Africa.
Today many other compounds taken
from Nature's medicine cabinet are showing promise. And with
thousands of species as yet untapped for their chemical potions,
it's tempting to compare bioprospectors to the proverbial
kids in a candy store. But in fact, those sweet rewards sometimes
come at tremendous cost. Researchers are increasingly finding
themselves at odds with traditional healers in many parts
of the world, who have long made use of plants and animals
to treat various ailments, and with Nature herself, who does
not typically part with anything without ecological consequences.
That there is a need for new drugs
to combat AIDS, Alzheimer's and other ailments, however, goes
without saying. In addition, researchers are under mounting
pressure to find compounds to replace those that have become
less effective. With bacterial resistance on the rise, for
example, the world desperately needs new antibiotics. The
same holds true for cancer drugs, which can lose their potency
in a patient over time. And Nature may still be the best place
to hunt for such lifesaving compounds.
Finding the Needle in the Haystack
With about 10 million species inhabiting the earth, how do
scientists determine which ones contain potential panaceas?
In many cases they are screening randomly — a process
that yields on average one useful drug for every 20,000 samples
analyzed. But other researchers employ a different strategy,
consulting indigenous people when possible. According to Conservation
International, studies have shown that plants identified by
locals are in fact up to 60 percent more likely to have pharmaceutical
potential than their randomly collected counterparts.
Recently plants and sessile or slow-moving
marine invertebrates such as sponges, corals and sea slugs
have attracted particular attention because for these organisms,
running away from a predator is not an option. Instead they
have chemical defenses. And with a little tweaking, the potent
toxins they produce — as well as those manufactured
by certain poisonous snakes, frogs and land invertebrates
— can actually save lives.
DRUGS
FROM PLANTS
Many drugs in use today have their basis in
wild plants. A small selection of these are shown here:
Drugs
derived from wild plants
|
Plant
|
Location |
Drug |
Use |
Willow |
Worldwide |
Aspirin |
Fever and pain |
| Cinchone |
Tropics |
Quinine |
Malaria |
| Rosy
Periwinkle |
Madagascar |
Vincristine |
Leukemia |
| Rosy
Periwinkle |
Madagascar |
Vinblastine |
Hodgkin's
disease |
| Pacific
Yew |
Pacific
Northwest |
Taxol |
Ovarian
cancer |
| Opium
Poppy |
Eurasia,
Africa |
Morphine |
Pain |
| Curare |
Amazon |
Tubocurarine |
Muscle
relaxant |
| Snakeroot |
India |
Reserpine |
Hypertension |
| Foxglove |
Eurasia,
Africa |
Digoxin |
Cardiac
arrhythmia |
Of
course, targeting a promising compound is only the first
step. Before developing a drug from it, a renewable resource
for the compound has to be established. This task poses
an enormous barrier. Because these compounds often come
from rare or slow-growing organisms, or are produced in
minute quantities, harvesting the source organisms in sufficient
amounts may be unrealistic.
To address this problem, researchers
usually try to make synthetic derivatives. But sometimes
synthesis proves impossible, or uneconomical, as in the
case of Ecteinascidin-743, an anticancer compound currently
in clinical trials that comes from a creature called a sea
squirt. Scientists from CalBioMarine Technologies in Carlsbad,
Calif., have developed a method of culturing the animal,
going so far as creating an artificial version of the mangrove
roots it settles on in the wild. In other cases, simply
culturing cells from the source organism is sufficient.
Once developed, these drugs, as
with all proposed pharmaceuticals, must pass a battery of
rigorous test that evaluate their safety and efficacy in
animals and then humans. This step, too, can take its toll,
especially on start-up companies. Take, for example, the
case of Shaman Pharmaceuticals, a once-promising company
armed with a product poised to treat people suffering from
chronic diarrhea. Their drug, Provir — derived from
the sap of croton, a common Amazonian tree—did so
well in two years of clinical trials that the FDA granted
it fast-track status, requiring only one final Phase III
trial instead of two. When the FDA later decided to demand
a second Phase III trial, though, Shaman couldn't afford
it. Today the company sells dietary supplements.
Bioprospecting or Biopiracy?
In addition to the difficulties
posed by the research itself, the scientists and pharmaceutical
companies hunting for natural miracle drugs face critical
ethical dilemmas. In Brazil, for example, officials have
expressed concern over the possibility that the scientific
demand for plant samples has led to plant smuggling. And
indigenous groups around the world worry that in the race
to patent Nature's million-dollar molecules, science is
stealing their intellectual property.
Indeed, according to a report that
appeared earlier this year in the Atlanta Journal and Constitution,
even a project that aimed to share future profits with the
native people — Mayans in Mexico's Chiapas state —
has floundered, owing to disagreements over who owns the
plants, folk knowledge and commercial rights to whatever
drugs might result from the collaboration.
Other efforts to ensure these often
poorer nations benefit from visits from bioprospectors have
had happier outcomes. In South America's Suriname, for instance,
Bristol Myers-Squibb, scientists and conservationists from
the Missouri Botanical Gardens, the Virginia Polytechnic
Institute and Conservation International helped to establish
a four-million-acre reserve. Conservation International
has also been active in helping the governments of Madagascar
and Indonesia to develop policies aimed at maintaining national
sovereignty over their biological resources.
On the Horizon
Bioprospecting during the past
decade has yet to turn up a blockbuster drug, but a number
of naturally derived pharmaceuticals are being evaluated
in human trials. These include compounds ranging from Immunokine,
derived from the venom of the Thailand cobra, which may
effectively combat multiple sclerosis, to calanolide A,
an anti-HIV agent retrieved from a Malaysian plant. Ziconotide,
a potent pain reliever extracted from the tropical marine
cone snail, has come particularly far and is awaiting FDA
approval. Once approved, Ziconotide will become the first
marine-organism-based pharmaceutical.
In many cases, though, the environments
in which potentially healing organisms live are being destroyed.
Estimates place the number of species screened for their
medicinal properties at a mere 1 percent, yet each year
more than 30 million acres of tropical forest are lost.
Human activity is taking its toll on the oceans, too, in
the form of pollution and overfishing. Such large-scale
destruction of our planet's complex ecosystems will no doubt
come back to haunt us — if for no other reason than
the fact that with every species lost, Mother Nature is
taking potentially lifesaving chemical formulas to the grave.
©
1996-2003 Scientific American, Inc.
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Phytotherapie