|
||||||||||||||||
|
||||||||||||||||
The following HTML text is provided to enhance online readability. Many aspects of typography translate only awkwardly to HTML. Please use the page image as the authoritative form to ensure accuracy. Page 71 PART II
|
||||||||||||||||
 |
 |
Page 71 |
 |
 |
 |
|
| ||||||||||||||||||||||||||||||||
|
|
|||||||||||||||||||||||||||||||
Below are the first 10 and last 10 pages of uncorrected machine-read text (when available) of this chapter, followed by the top 30 algorithmically extracted key phrases from the chapter as a whole.
Intended to provide our own search engines and external engines with highly rich, chapter-representative searchable text on the opening pages of each chapter.
Because it is UNCORRECTED material, please consider the following text as a useful but insufficient proxy for the authoritative book pages.
Do not use for reproduction, copying, pasting, or reading; exclusively for search engines.
OCR for page 71
Page 71
PART II
VALUE OF MARINE BIODIVERSITY TO BIOMEDICINE
In Part I, threats to human health from the ocean were defined
and identified as areas that would benefit from greater interaction
between the oceanographic and medical communities. For example,
research on the ecology of harmful algal blooms addresses problems
relevent to both public health and environmental health.
Sentinel species like marine mammals, fish, and birds provide
initial indicators of environmental problems such as a harmful
algal bloom. Tests to detect Florida red tide and ciguatera,
developed for emergency room use, were used to identify red tide
brevetoxin as the reason for manatee deaths in 1996. The cause of
gannet and other sea bird deaths in 1995 was linked to paralytic
shellfish poisoning, using techniques developed to study human
nerve function. Using tests developed for molecular brain research,
the lethal agent responsible for mortality of sea lions in Monterey
Bay was identified as the algal toxin that causes amnesic shellfish
poisoning. Animal model system work, funded by the National
Institutes of Health (NIH), has provided answers to how toxins are
accumulated and how these toxins affect nerves and metabolism. This
knowledge provides clues to potential antidotes, therapies, and
treatments. Hence, studies of marine toxins not only help prevent
human illness and identify environmental problems but also provide
insight into human biology and suggest new approaches for treating
human diseases.
In the second half of this report, research areas are defined
that establish the basis for a unique partnership—a
cross-fertilization that provides for an interactive approach to
the ocean and human health. Ways in which issues common to
different areas of marine research areas will help provide answers
or approaches of value to the others are summarized in the table
below:
OCR for page 72
Page 72
TABLE PART II Interactive Elements of HABs, Marine
Models, and Drug Discovery
Harmful Algal Blooms
Drug Discovery Programs
Marine Models of Human Disease
Environmental chemicals that affect man
Known and emerging toxins
Surveys for new agents
Test system for identification, including
sentinels
High throughput assays
Needed
Available
Receptor basis for development
Mechanism of action
Known but need detail
Bioassay-guided
System for deciphering
Model system
Need sensitive and specific models
Models needed for specific actions
Disease-based
Therapeutics
Need for each toxin type
Potential for specific diseases
In vivo system for development
The research described in the following chapters falls under the
category of marine biotechnology. Several previous reports have
argued that the investment in marine biotechnology in the United
States should be higher (NRC, 1994a; Zilinskas. 1995). For example,
approximately one patent is issued for every $1.1 million spent on
marine biotechnology, an indication of the high productivity of
this research. Despite this success, it is estimated that only 1.1%
of the nation's biotechnology budget was spent on research in
marine biotechnology in 1992 (Zilinskas, 1995). Also, the absolute
level of funds spent for marine biotechnology has been low compared
to the investment made in other countries; in 1991, the U.S. spent
between 7–10% of the amount spent in Japan on marine
biotechnology (Zilinskas, 1995). The following chapters illustrate
the potential of two areas of marine biotechnology, marine natural
products and marine biomedical models. In Chapter 4, the principle
of using marine biotoxins and other compounds from marine organisms
as molecular probes in biomedical research is discussed in the
larger context of how marine natural products provide a new source
of molecular diversity that will be of value in developing new
pharmaceuticals. Chapter 5 illustrates how basic research on marine
organisms offers insights into disease processes that occur in
humans.
OCR for page 73
Page 73
4
Marine-Derived Pharmaceuticals and Related Bioactive Agents
One of the major accomplishments of the 20th century is the
development of modern pharmaceuticals. Since their emergence early
in the 20th century, drugs such as penicillin, streptomycin, and
vincristine, among others, have contributed significantly to the
management of human disease. New drug therapies have extended human
life span and improved the quality of life. In this regard, society
has become more and more reliant upon the availability of safe and
efficacious pharmaceutical products.
Nature has been the traditional source of new pharmaceuticals.
Today, over 50% of the marketed drugs are either extracted from
natural sources or produced by synthesis using natural products as
templates or starting materials. Since ancient times, early
societies used natural medicines, generally as crude extracts from
plants, to treat infection, inflammation, pain, and a variety of
other maladies. Even today, in many parts of the world, natural
medicines provide the only treatments available. Investigation of
these ''natural" ethnobotanical preparations led to the isolation
of compounds whose beneficial properties have provided the
foundation of the current pharmaceutical industry.
Of course, times have changed and science in both industrialized
and developing nations has become much more sophisticated in its
approach to drug discovery. Complex programs have been initiated to
investigate diseases based on their fundamental biochemical and
molecular causes. In some cases, it has been feasible to design
drugs based on knowledge of an appropriate biochemical target. In
other instances, new drugs have been discovered by modern
high-through-put screening, a process in which thousands of natural
or synthetic chemicals are tested in automated pharmacological
bioassays. All of these approaches have a place in the discovery
process, but without a natural product to lead science to its
OCR for page 74
Page 74
biological target, many drugs would never have been developed.
It appears that a diverse approach, involving all these methods, is
the most effective approach. It is also clear that natural
products, which have evolved over millions of years of selective
pressures, provide one of the most important components of this
process.
There is a continual need for new therapeutic agents, especially
to treat a large variety of diseases for which there are no
effective therapies. Many forms of cancer, viral and fungal
infections, inflammatory diseases, and neurodegenerative diseases
cannot be treated successfully. Development of resistance of
pathogenic microorganisms to antibiotics and cancer cells to
antitumor drugs requires the compensatory generation of new drugs.
The pathogens responsible for malaria and tuberculosis have
developed resistance to most available drugs. Thus, heavy
investment in the development of new antibiotics will be necessary
in the next millennium.
This chapter will address the issue of new drug discovery. As in
the past, natural products will be an important source of new
therapeutics, but it is necessary to identify sources of new
biological activities and chemical structural diversity. As
described below, the biological diversity of the ocean offers great
promise as a source of drugs for the future.
The Marine Environment as a Source of
Chemical Diversity
Representatives of every phylum are found in the sea; twelve
phyla are exclusively marine. The ocean contains more than 200,000
described species of invertebrates and algae (Winston, 1988),
however, it is estimated that this number is but a small percentage
of the total number of species that have yet to be discovered and
described. Conservative estimates suggest that oceanic subsurface
bacteria could constitute as much as 10% of the total living
biomass carbon in the biosphere (Parkes et al., 1994). From a
relatively small number of these species that have been studied to
date, thousands of chemical compounds have been isolated (Ireland
et al., 1993). Moreover, only a small percentage of these compounds
has been tested in clinically relevant bioassays. The ocean
represents a virtually untapped resource for discovery of novel
chemicals with pharmaceutical potential.
Marine plants, animals, and microbes produce compounds that have
potential as pharmaceuticals. These "secondary metabolites,"
chemicals that are not needed by the organism for basic or primary
metabolic processes, are believed to confer some evolutionary
advantage. Because many of these plants and animals live in densely
populated habitats (Plate X), are non-motile, and have only
primitive immune systems, they have evolved chemical compounds to
help defend against predators (Paul, 1992), to attract or inhibit
other organisms from settling
OCR for page 75
Page 75
or growing on them (Pawlik, 1993), and to provide chemical cues
to synchronize reproduction among organisms that expel their eggs
and sperm into the water (Morse, 1991). The mechanisms by which
they prevent encroachment or predation interact with the same or
similar enzymes and receptors that are involved in human disease
processes. For example, many natural products have been identified
that inhibit cell division, the process that is the primary target
of many anti-cancer drugs. In most cases, there is a greater
understanding of the effect of the natural product on human disease
processes than of the function in the marine organism from which it
was isolated.
The marine environment became a focus of natural products drug
discovery research because of its relatively unexplored
biodiversity compared to terrestrial environments. The potential of
marine natural products as pharmaceuticals was introduced by the
pioneering work of Bergmann in the 1950s (Bergmann and Feeney,
1951; Bergmann and Burke, 1955), which led to the only two
marine-derived pharmaceuticals that are clinically available today.
The anticancer drug, Ara-C, is used to treat acute myelocytic
leukemia and non-Hodgkin's lymphoma. The antiviral drug, Ara-A, is
used for the treatment of herpes infections (McConnell et al.,
1994). Both are derived from nucleosides isolated from a
shallow-water marine sponge collected off the coast of Florida.
Marine sponges are among the most prolific sources of diverse
chemical compounds with therapeutic potential (Plate XI). Of the
more than 5000 chemical compounds derived from marine organisms,
more than 30% have been isolated from sponges (Ireland et al.,
1993). Sponges occur in every marine environment, from intertidal
to abyssal regions, in all the world's oceans, and they produce a
greater diversity of chemical structures than any other group of
marine invertebrates. Other marine sources of bioactive molecules
with therapeutic potential are bryozoans, ascidians, molluscs,
cnidarians, and algae. Several strains of phytoplankton, especially
cultured species of diatoms, have been described as exhibiting
antibacterial and antifungal activity (Viso et al., 1987). However,
the levels of activity are low and hence the active compounds have
not yet been isolated or characterized.
The Discovery and Development of
Marine
Pharmaceuticals: Current Status
Since the mid-1970s, academic, government, industrial, and
private research laboratories have devoted varying levels of effort
to the discovery of marine-derived pharmaceuticals. The major
emphasis has been on the discovery of anti-cancer compounds, due in
large part to the availability of funding to support marine-based
drug discovery. The National Cancer Institute (NCI) has led this
effort through its aggressive programs to support both
single-investigator and
OCR for page 76
Page 76
multi-institutional cancer drug discovery research. As a result,
several marine-derived compounds are in clinical trials for the
treatment of cancer.
Bryostatin, isolated from the bryozoan Bugula neritina,
is a polyketide with both anticancer and immune modulating activity
(Kalechman et al., 1982; Pettit et al., 1996; Philip et al., 1993;
Suffness et al., 1989). Its mechanism of action is through
activation of protein kinase C mediation of cell signal
transduction pathways. This compound is currently in Phase II
clinical trials for non-Hodgkin's lymphoma, chronic lymphocytic
leukemia, and multiple myeloma through a Cooperative Research and
Development Agreement (CRADA) between the NCI and Bristol-Myers
Squibb.
Ecteinascidin 743, a complex alkaloid derived from the ascidian
Ecteinascidia turbinata (Rinehart et al., 1990; Wright et
al., 1990) and licensed by the University of Illinois to PharmaMar
S.A. is in Phase I clinical trials for ovarian cancer and other
solid tumors in the United States and Europe.
Discodermolide, a polyketide isolated from deep-water sponges of
the genus Discodermia (Plate XIIa; Gunasekera et al., 1990)
is a potent immunosuppressive and anticancer agent which inhibits
the proliferation of cells by interfering with the cell's
microtubule network (Plate XIIb and c; Longley et al., 1991a and b;
ter Haar et al., 1996). This compound may be effective against
breast and other types of cancer that have become resistant to
other microtubule disrupting drugs. Discodermolide has been
licensed by Harbor Branch Oceanographic Institution (Fort Pierce,
FL) to Novartis Pharmaceutical Corporation, and is in advanced
preclinical trials.
Another promising sponge metabolite in advanced preclinical
trials at the NCI is halichondrin B, derived from a New Zealand
deep water sponge, Lissodendoryx sp. (Hirata and Uemura,
1986; Litaudon et al., 1994). Like discodermolide, halichondrin B
blocks cell division by disruption of microtubule structure.
In each of these cases, however, bulk supply of the chemicals
for continued clinical development is a problem. It is often
neither economically nor ecologically feasible to rely on
large-scale collections of the source organisms from their natural
habitats for supply of marine drug candidates. Whether a drug
company decides to support the clinical development of a new drug
is dependent on identifying an adequate supply of the source
material. This could be through culture of the organism or through
synthesis of the compound using an economically feasible,
industrial-scale process. Research is in progress on options for
biological supply (e.g., aquaculture, cell culture, microbial
fermentation, and genetic engineering) to address this critical
issue in the development of chemicals from natural sources.
Unfortunately, neither the NIH nor must drug companies are prepared
to invest funds in basic research to develop general models for
biological supply of marine natural products with therapeutic
potential.
Despite the emphasis on identifying new anticancer compounds,
marine natural products have also been found to have other
biological activities, including
OCR for page 77
Page 77
mediation of the inflammatory response. The pseudopterosins are
glycosides derived from the Caribbean soft coral
Pseudopterogorgia elisabethae (Plate XIII; Look et al., 1986;
Roussis et al., 1990). These are in advanced preclinical trials as
anti-inflammatory and analgesic drugs.
A number of marine-derived compounds have been discovered with
antiviral and antifungal activity. Indeed, one of the two
clinically-available marine-derived drugs is used for the treatment
of herpes infections. Although no marine natural products are
currently in clinical trials as treatments of infectious diseases,
there is high potential for future development.
Marine Microorganisms as a Novel
Resource for New Drugs
Since the discovery of penicillin in the late 1920s,
terrestrial, mainly soil-derived microorganisms have provided the
single most important resource for discovery of new drugs. Over 120
microbially-produced drugs are in clinical use today to treat
infectious diseases, cancer, and to facilitate organ
transplantation by suppression of the immune response. Examples of
these highly used drugs are the antibiotics, such as the
penicillin, cephalosporines, streptomycin, and vancomycin, the
cancer drugs actinomycin and mitomycin, and the immunosuppressant
drug cyclosporin. Not only have microorganisms been a tremendous
source of biodiversity and chemical diversity, but their capacities
to produce highly complex molecules from common nutrients in
fermentation culture have led to their widespread use in the
economic, industrial-scale production of drugs. Today, the
pharmaceutical industries worldwide (but particularly in the United
States and in Japan) continue to rely on microorganisms as the
single most useful source for natural product drugs.
But there are growing concerns about the continuance of this
historic approach to drug discovery. Over the past 50 years,
soil-derived microorganisms have been extensively investigated from
virtually all terrestrial regions of the Earth. Literally millions
of isolated microbial strains have been extensively evaluated in a
large variety of pharmacological bioassays. Although these
microorganisms were at one time a rich source of novel chemical
compounds, much of their chemical diversity has been exploited. New
antibiotics are not being developed as before. Anticancer drugs,
possessing radically new chemical formulations, are not being found
at the rate once observed. Depending upon the area of
investigation, it has been observed that greater than 95% of the
"active" molecules identified are actually molecules discovered in
the past. This extensive duplication of discovery has required the
development of sophisticated "dereplication" schemes, which are
designed to quickly discard well-known substances that frequently
recur. More important, the costs of new discoveries have escalated.
These costs are so high that the pharmaceutical industry has
invested in a more cost efficient process, "high-throughput
OCR for page 78
Page 78
screening," which allows literally hundreds of thousands of
samples to be evaluated in weeks to months, rather than years.
Most of the Earth's microbial diversity is found in the ocean.
In addition to the typical organisms found on land, many classes of
microorganisms exist only in the sea. The photosynthetic
microorganisms alone comprise over 12 plant divisions. With the
inclusion of the known unique adaptations of microorganisms to high
salt environments and high hydrostatic pressure, the immense
diversity of the microorganisms in marine habitats becomes
apparent. However, the pharmaceutical industries have not taken
advantage of this enormous resource. The reason rests with the
tendency of researchers to explore familiar and more readily
accessible microorganisms. In the 1950s, it was reported that fewer
than 5% of the marine bacteria present in environmental samples
could be cultured. This led to the widespread belief that marine
microorganisms were simply unculturable. This, together with the
traditional lack of cross-disciplinary interaction between marine
and medical microbiology, resulted in a great hesitation to embark
on an aggressive marine-oriented program. With no guarantees that
any new drugs will be found, the risk was difficult to justify.
However, times have changed and marine microorganisms can now be
cultivated successfully (Davidson, 1995; Fenical, 1993; Kobayashi
and Ishibashi, 1993; Okami, 1993). The microbial diversity of the
marine environment has thus become available for scientific study,
and new programs are emerging worldwide. In the United States and
Japan, intense focus on coastal sediments and organisms associated
with marine invertebrates has resulted in a growing number of
papers documenting the production of novel, bioactive metabolites.
Both bacteria and fungi are now the target of biomedical study, and
fascinating reports of novel metabolites are becoming more and more
common. Bacterial samples from coastal sediments, when grown under
saline conditions, have yielded new antibiotics, antitumor, and
anti-inflammatory compounds (Pathirana et al., 1992; Trischman et
al., 1994a, b). Similarly, when the surfaces of marine plants and
the internal tissues of invertebrates have been sampled, bacteria
and fungi have been discovered that also produce bioactive
compounds with pharmaceutical potential. Marine fungi, in
particular, seem to be the focus of increasing interest (Belofsky
et al., 1998; Cheng et al., 1994; Kakeya et al., 1995; Numata et
al., 1992; Takahashi et al., 1995).
A unique source in the world's oceans, the deep ocean and the
geothermal vents, is now becoming the focus of considerable
microbiological interest. Microbiological studies of the deep sea
environment have shown the presence of obligate barophiles,
bacteria which require pressures as high as 600 atmospheres for
growth to occur (Yayanos, 1995). These highly adapted marine
microorganisms represent a biomedical resource of unknown
magnitude, but great promise, as demonstrated recently when unusual
compounds produced by bacteria retrieved from deep sea drilling
cores were shown to inhibit colon tumor cell growth and prevent
replication of HIV, the AIDS virus (Gustafson et al., 1989).
OCR for page 79
Page 79
The Marine Environment as a Source of
Molecular Probes
One important application of the many bioactive compounds
derived from the marine environment is their use as molecular
probes, molecules broadly defined as non-drug substances which can
be used to probe the foundations of important biochemical events.
Molecules such as the potent marine neurotoxins, tetrodotoxin,
saxitoxin, conotoxin, lophotoxin, and others, have been
instrumental in defining the functions and overall structures of
the membrane channels which facilitate nerve transmission.
Knowledge of the function of these neurotoxins has allowed drugs to
be designed and targeted to those sites of nerve transmission.
Other examples are the discovery that the dinoflagellate toxin,
okadaic acid, shows potent and selective inhibition of
phosphatases; the utilization of the anti-inflammatory agent,
monoalide, as a selective inhibitor of the inflammation enzyme
phospholipase A2 (Glaser and Jacobs,
1986); the use of latrunculin A, jaspamide (jasplakinolide), and
swinholide A as selective binding agents to the intracellular actin
network (Bubb et al., 1995; Matthews et al., 1997; Senderowicz et
al., 1995); and the recent discovery of the unique sponge
metabolite, adociasulfate-2, which selectively inhibits the
intracellular molecular motor protein kinesin (HHMI, 1998). The
importance of molecular probes in resolving the complexities of
diseases and cellular processes has often outweighed any value that
they would have as commercial drugs.
Marine natural products have not only contributed probes for
studying specific cellular proteins and enzymes, but they have also
provided visual markers for proteins specified by antibodies, for
cellular events mediated by calcium, and for elucidating mechanisms
of tissue-specific gene expression. Antibodies are an indispensable
tool of molecular biology and biomedicine because they can be used
to identify specific biomolecules. However, they must be coupled to
a reporter molecule, usually an enzyme with a colorimetric
substrate or a fluorescent compound. Phycoerythrin, a fluorescent
protein isolated from red algae, is crosslinked to antibodies for
use as an indicator in many immunological assays. In the algae,
phycoerythrin functions in light harvesting during photosynthesis.
For this role, the protein shows optimization of both absorption
and fluorescence resulting in high quantum yield while showing
minimal dependence on pH or ionic conditions. (Glazer, 1988; 1989)
These properties make it ideal for assays requiring high
sensitivity (quantum yield is 30–100 times greater than the
chemical dyes fluoresein and rhodamine); therefore
phycoerythrin-conjugated antibodies are a favored reagent for use
in flow cytometry, a common clinical diagnostic procedure (Roederer
et al., 1997; Sohn and Sautter, 1991).
Aequorin, a compound isolated from a bioluminiscent jellyfish
Aequora victoria has been used extensively in cell biology
because it has the unique property of emitting light in the
presence of calcium. For example, aequorin has been
OCR for page 80
Page 80
used to illuminate the calcium wave during sea urchin egg
fertilization (Eisen and Reynolds, 1985) a phenomenon described in
greater detail in Chapter 5. The photoprotein component of aequorin
has been cloned into gene expression vectors, and is currently used
to monitor calcium in the cytoplasm and organelles of tissue
culture cells (Badminton and Kendall, 1998; Badminton et al., 1995;
Brini et al., 1994; Montero et al., 1995; Rutter et al., 1993).
Recently, there has been an exciting new development of another
product derived from the bioluminescent jellyfish A.
victoria, the cloning of green fluorescent protein (GFP)
(Chalfie et al., 1994). In jellyfish, GFP absorbs the blue light
produced by aequorin and fluoresces green light. GFP has been
developed for use as a reporter gene in numerous studies on the
regulation of gene expression (Plate XIV). Because GFP fluoresces
in living tissues, it is now possible to monitor gene expression
continuously, a property of particular value in the study of
differentiation in both embryos and tissue culture cells.
There are many other marine products that have contributed to
basic and clinical research including enzymes for molecular
biology, most notably the Vent DNA polymerase used in the
polymerase chain reaction (PCR). PCR, a technique used to amplify
minute amounts of DNA or RNA, requires the use of enzymes that are
stable at high temperature. A marine microorganism isolated from
the deep sea hydrothermal vents yielded the Vent DNA polymerase
which is used in high fidelity PCR reactions common to both
diagnostic procedures and the gene mapping studies of the Human
Genome Project. Marine bacteria have also provided many unique
restriction enzymes used in the cloning of DNA. Since we have only
begun to investigate marine biodiversity, it is reasonable to
expect that marine molecular probes will continue to advance the
frontiers of molecular and cellular biology.
The Ocean as a Source of New
Nutritional Supplements
Docosahexonoic acid (DHA) and arachidonic acid (ARA) are the
most abundant polyunsaturated fatty acids (PUFAs) in breast milk,
and are the predominant structural fatty acids in brain gray
matter. High dietary levels of these PUFAs are believed to result
in higher levels in the brain, and they have been recommended as
nutritional supplements for infants. A marine microalgal species
has been discovered that produces large quantities of the
fatty-acid docosahexenoic acid (DHA). It is used in an infant
formula supplement Formulaid® (Martek Biosciences, Columbia,
MD). Marine-derived nutritional supplements, or "nutriceuticals,"
present a new opportunity for research in the application of marine
natural products to human health issues.
OCR for page 81
Page 81
Conclusions
The Discovery and Development of
Marine Pharmaceuticals:
Needs for the 21st Century
• Marine organisms as a source of pharmaceuticals
The successes to date in the discovery of novel chemicals from
marine organisms that have demonstrated potential as new treatments
for cancer, infectious diseases, and inflammation, suggest that
there needs to be a greater focus on the development of drugs from
marine sources. Exploration of unique habitats, such as deep sea
environments, and the isolation and culture of marine
microorganisms offer two underexplored opportunities for discovery
of novel chemicals with therapeutic potential. The successes to
date based on a very limited investigation of both deep sea
organisms and marine microorganisms suggests a high potential for
continued discovery of new drugs. Marine microorganisms are
particularly attractive because they fit in with the traditional
pharmaceutical "model" of a natural product drug source. Moreover,
supply of bulk amounts of a microbially-derived drug can be
addressed by large-scale fermentation of bioactive marine
microorganisms.
• Expand marine drug discovery beyond cancer to include
other diseases
Programs such as the Natural Products National Cancer Drug
Discovery Groups (NPNCDDGs) at the National Cancer Institute have
been tremendously successful in interfacing non-traditional drug
sources, such as marine organisms, with the screening and
development potential of major pharmaceutical companies. Similarly,
the Small Business Innovative Research (SBIR) grants have fostered
interactions on a smaller scale. Other institutes within the NIH
should consider developing programs for marine-based drug discovery
for diseases that desperately need new therapies, such as
neurodegenerative, cardiovascular, and infectious diseases.
In particular, there needs to be a more organized approach to
the development of antibiotics from marine sources. The
increasingly limited effectiveness of currently available drugs has
dire consequences for public health, although the consequences have
not yet been felt by the public or the medical community. The
United States is faced with the serious threat of re-emerging
infectious diseases, such as tuberculosis, indicating that a
radical and aggressive approach needs to be taken to control these
multiple-drug-resistant pathogens.
• New interdisciplinary research and education programs
Few researchers have training in both medicine and marine
science. Cross-training in both disciplines could provide
innovative approaches to marine-based biomedical research. For
example, marine organisms have already demonstrated their utility
as biomedical models, the results of which have been applied to
understanding normal and disease processes in humans (cf. Chapter
5). Marine
OCR for page 82
Page 82
organisms also offer the potential to understand and develop
treatments for disease based on the normal physiological role of
their secondary metabolites. In some systems, e.g., Conus
toxins (Hart, 1997; Hopkins et al., 1995), the mechanisms of action
of the metabolites are well-known and can be applied to the
development of new classes of drugs. In most systems, however, the
natural functions of bioactive secondary metabolites are poorly
understood. The respective expertise of marine and medical
scientists should be optimized and the cross-training of marine and
biomedical scientists should be encouraged to study the role of
these compounds in nature, to determine how chemical interactions
in the ocean can be applied to the development of new drugs, and
then to design appropriate bioassays to test their effectiveness
against human diseases. One possible way to achieve this goal would
be to develop a new graduate student training initiative. The
purpose of the program would be to educate graduate students in
both marine and medical sciences and to facilitate the development
of a strong interface between medicine and marine sciences.
Representative terms from entire chapter:
drug discovery