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One
sponge discovered by Faulkner in Palau was found to contain a substance
named manoalide, which inhibits the action of an enzyme called phospholipase
A2. This enzyme plays a key role in the biochemical processes that
lead to pain and swelling from inflammatory conditions such as arthritis,
psoriasis, and poison oak.
Fenical
also has discovered a potent anti-inflammatory agent, called pseudopterosin.
The compound, which is extracted from a Caribbean sea whip, already
has been incorporated into a skin cream currently being marketed
as a protection against sun damage. Pseudopterosin also has been
licensed to a pharmaceutical firm, which is testing it as an anti-inflammatory
drug against such conditions as contact dermatitis.
The compound, developed in conjunction with Robert Jacobs, a professor
of pharmacology at UC Santa Barbara, is among the University of
California's top ten royalty producing inventions. It generated
$686,000 in royalties in fiscal year 1994-1995.
Fenical’s and Faulkner’s works on marine-based pharmaceuticals
stemmed from their earlier interests in the roles chemicals play
in the ecology of the ocean. The scientists wanted to learn more
about how marine organisms use chemical compounds to signal each
other, to ward off predators, and to mate.
...we
started to get all of these weird and wonderful compounds
and we said, ‘Why aren’t we looking at these things
in the context of doing some medical research?’" |
"To
begin with it was really pure academic interest in how the ocean
works, especially in highly competitive tropical environments
where everything is trying to eat everything else," said
Fenical. “Then we started to get all of these weird and wonderful
compounds and we said, 'Why aren’t we looking at these things
in the context of doing some medical research?'"
The
research of Fenical and Faulkner is funded by the National Cancer
Institute, the National Science Foundation, and the California
Sea Grant College System. In addition to teaming up with pharmaceutical
companies, the two scientists also collaborate with Stephen Howell,
a cancer pharmacologist at UC San Diego’s Cancer Research
Center. Howell originally conceived the idea of working with Scripps
to develop new marine-based cancer drugs. While Scripps researchers
would collect and screen novel marine compounds, the cancer center
would perform preclinical biological research and ultimately conduct
clinical trials at UC San Diego Medical Center.
"It would be a first for a college campus to develop a drug
from start to finish," Fenical said. “Academic scientists
traditionally do not have the capability to discover, develop,
and clinically evaluate a cancer drug within the same facility."
It
is hoped that the Center for Marine Biotechnology and Biomedicine
will be able to expand its current working relationship with pharmaceutical
companies by encouraging them to invest more heavily in marine
natural products research.
Fenical believes that such a bridge between marine science and
medicine could ultimately lead the way to new cures for the diseases
that still plague us, such as cancer and AIDS.
"The oceans are the next great biomedical frontier—there
is no question in my mind about that," he said. “The
degree to which we will find cures for diseases in the world’s
oceans, however, will be equivalent to our ability to invest in
exploring the resources they offer."
Email
the author: Janet
Howard
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Back
in the Lab
 When
Sir Alexander Fleming discovered penicillin in bread mold in 1928,
he sparked a revolution in drug development.
Researchers began diligently sifting through soil and plants in
search of new weapons to fight disease. Indeed, many of today’s
pharma-ceuticals originated in terrestrial sources. Morphine comes
from the opium poppy. Aspirin is found in the bark of a willow
tree. Digitalis, a heart medication, comes from the foxglove plant.
Bacteria, fungi, and other soil microbes also give rise to an
army of antibiotics and antifungals used to treat everything from
strep throat to pneumonia.
A rise in the number of infectious agents that are resistant to
known antibiotics, however, has scientists beginning to look to
the tiniest organisms in the sea as new sources of drugs.
“For 60 years, people have spent huge amounts of money scrounging
through dirt to find microorganisms to produce drugs, and there
are more than a hundred such drugs on the market right now,"
said Bill Fenical. “It is clear, however, that we need to
find new resources to supplement those upon which we have traditionally
relied."
While Fenical continues to direct a laboratory that concentrates
on finding novel compounds in larger marine organisms, such as
soft corals, he established a new lab about six years ago that
focuses exclusively on microbial agents found in the ocean.
The lab, soon to be expanded and renamed the Charmaine and Maurice
Kaplan Cancer Drug Dis-covery Laboratory, centers around two walk-in
refrigerators stacked to the ceiling with large glass flasks filled
with sometimes scary-looking microbes. The flasks, many of which
are continually shaken on oscillating shelves to provide adequate
oxygenation, contain organisms that have been singled out as showing
enough potential to warrant future study. They have been selected
from hundreds of specimens that are grown in the culture plates
that fill the lab’s shelves.
Researchers extract compounds from the flasks and pour them into
tall, column-shaped beakers containing organic solvents in order
to separate them into their various components. These purified
chemicals are then put through a variety of tests, including a
bioassay to determine if they are effective in killing human cancer
cells. Those showing promise are identified using nuclear magnetic
resonance spectrometry, a method that allows a scientist to identify
each atom in a molecule’s structure.
The enthusiasm of the dozen graduate students, postdoctoral fellows
and researchers who work in the lab is unmistakable.
“We’re bioprospectors," said Gil Belofsky, a postdoctoral
research scientist, taking a break from working over five giant
flasks filled with goopy-looking mold. “We’re moving
into the next generation of marine natural products."
Fenical stated that one of the greatest advantages of working
with marine microbes rather than larger marine organisms is that
microbes can be cultured and grown in the lab rather than having
to be continually collected from the sea. Because pharmaceutical
companies already operate large fermentation plants where they
grow terrestrial microbes, it is also much easier for them to
incorporate marine microbial agents into their drug development
programs.
“The beauty of it is even though the terrestrial source for
microorganisms is becoming very scarce, the pharmaceutical companies
don’t have to dramatically change what they are doing,"
Fenical said. “You can hand them a batch of marine microorganisms
and some table salt and say, ‘Just grow it in seawater and
you can do everything with these the same way you have been doing
it for the last 25 years.’" |
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