From Monsoons to Microbes Understanding the Ocean's Role in Human Health (1999) / Chapter Skim
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4 Marine-Derived Pharmaceuticals and Related Bioactive Agents
4 Marine-Derived Pharmaceuticals and Related Bioactive Agents
Pages 71-82
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From page 71... ...
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.
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From page 72... ...
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.
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From page 73... ...
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.
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From page 74... ...
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~.
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From page 75... ...
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.
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From page 76... ...
to address this critical issue in the development of chemicals from natural sources. Unfortunately, neither the NIH nor most drug companies are prepared to invest funds in basic research to develop general models for biological supply of marine natural products with therapeutic potential.
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From page 77... ...
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.
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From page 78... ...
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~.
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From page 79... ...
, 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.
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From page 80... ...
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.
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From page 81... ...
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.
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From page 82... ...
The respective expertise of marine and medical scientists should be optimized and the crosstraining 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.
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