2001–2002 - California Sea Grant - UC San Diego

Developing Methods for Producing Marine Compounds in Nonmarine Organisms
In the search for new medicines, no realm of the globe holds
more intrigue than that of the sea. Many of the more complex,
novel and interesting compounds discovered in the last decade have
been extracted from marine organisms—typically soft corals and sponges,
marine algae, even bacteria. Yet, despite the sea’s promise, as of mid-
2002, there was not a single marine-derived drug on the marketplace.
Why?
Sea Grant’s researchers and others say there are a few intrinsic difficulties.
A leading one is that marine animals often contain very low levels of a
desired compound, making it nearly impossible to collect enough of a
sample for extensive laboratory testing. Animals may also be rare or part
of a fragile ecosystem, which would be harmed by intense harvesting. Still
With Sea Grant funding, Dr. Margo Haygood has developed techniques that may
make it possible to produce marine natural products in nonmarine, easy-to-grow
organisms. Photo: Scripps Institution of Oceanography
24
other animals, even if they are common, may be extremely difficult to
collect.
As a result, it is often impractical to pursue developing drugs from wild
marine populations. Even in the best cases, drug discovery is a long shot.
Given the cost of developing new medicines, researchers and pharmaceutical
companies still opt to follow in the footsteps of the past by modifying
or synthesizing compounds extracted from terrestrial life.
In this Sea Grant project, marine biology professor Dr. Margo Haygood
of Scripps Institution of Oceanography was funded to investigate what
could lead to a commercially viable method for producing large quantities
of a marine compound in nonmarine, easy-to-grow animals. Because of
the obvious commercial applications, her experiments, and her findings,
have stirred great excitement within the scientific community as truly
making progress in efforts to develop techniques for mass-producing
scarce marine natural products. From a more general perspective,
Haygood’s research goes a long way toward unlocking the ocean’s treasure
chest of marine compounds for the treatment of human disease.
In her research, the compound of interest is Bryostatin 1, one in a
family of macrocyclic lactones called bryostatins. Bryostatins are found in
a brown, moss-like colonial marine animal, a bryozoan of the species
Bugula neritina. Since the 1980s, people have recognized the strong
anticancer properties of these compounds and have speculated, but not
shown, that bacterial symbionts are involved in their production. The
compounds are of added interest because, unlike many cancer treatments,
they do not kill cells directly but instead inhibit normal functioning of
proteins during cell replication, causing rapidly dividing cells to effectively
commit suicide. None of this knowledge, however, has been parlayed into
actually treating human disease.
After a series of experiments, Haygood was able to show that bacteria
living within B. neritina are indeed the source Bryostatin 1. Among the
facts that point to this conclusion, B. neritina were observed to contain
smaller amounts of bryostatin after being treated with antibiotics.