For thousands of years, humans have depended on a “natural pharmacy” stocked with extracts from plants, animals, and microbes to treat a wide variety of diseases and medical problems. Research has resulted in the isolation and use of pure drugs and bioactive compounds. Today, 40 to 50 percent of drugs being used to treat human illness are derived from natural products, the majority of which are derived from terrestrial organisms (Bruckner 2002). We have come to depend on a range of medical treatments derived from natural products, such as antibiotics, pain killers, cancer therapies, and anti-inflammatory drugs, in our daily lives, and as a society we expect and value the availability of new drug therapies.
Current therapies and medicines for some serious diseases do not completely control the target disease or are available in limited supply. With the emergence of antibiotic resistance in bacteria and the spread of devastating diseases such as AIDS, there is an urgent need for new drugs. After several decades discovery and intensive searching among land-based organisms, novel natural products from terrestrial organisms with promising chemical and pharmaceutical properties are becoming harder to find.
Researchers are now turning with high expectations to marine organisms in their hunt for new medicines and other important bioactive compounds. The ocean is home to over 80 percent of all life forms on Earth. Thirty-four out of the 36 phyla of life forms are represented in the oceans; in contrast only 17 phyla are present in terrestrial habitats. The promise of a rich new source of useful pharmaceuticals and bioactive chemicals lies in our oceans.
Marine organisms have evolved a wide variety of toxins and novel chemical adaptations that help them compete successfully in demanding environments, such as a crowded coral reef, pounding surf, deep ocean sediments, thermal vents, and Arctic waters. Many sessile marine organisms, in particular invertebrates such as corals, mollusks, sponges, echinoderms, and bryozoans, have evolved chemical weapons to help them compete for limited resources, avoid predation, or deter overgrowth by competitors. Scientists anticipate that some of these compounds will provide useful drugs, especially antibiotics and anticancer agents, as well as agricultural products, and industrial enzymes.
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Cultures of bacteria of the genus Salinospora.Image Courtesy: National Science Foundation |
Scientists are focusing their search for new marine bioproducts in habitats with high biodiversity and on marine microbial populations. Soil bacteria in the order Actinomycetes have already provided society with some of the most beneficial antibiotics and anticancer agents. Efforts to isolate marine actinomycetes from tropical ocean sediments have been extremely promising (Mincer et al. 2002). Members of Dr. William Fenical’s research team at the Scripps Institute of Oceanography have discovered at least 2,500 new species of marine bacteria, now called Salinospora, which are related to the land-based actinomycetes. More than 80 percent of these newly discovered bacteria demonstrate anticancer activity at very dilute concentrations. One compound, called Salinosporamide A, is a potent inhibitor of cancer growth, including human colon carcinoma, nonsmall cell lung cancer, and, most effectively, breast cancer (Feling et al. 2003). Salinosporamide A is currently in the process of completing Phase I clinical trials (National Institutes of Health 2009).
The use of marine organisms as pharmaceuticals and other useful products is not new. Eastern cultures have used marine organisms such as the sea horse, sea hares, and sponges in traditional medicines for centuries. Biotechnology opens new avenues for discovery. Several important drugs, including AZT (used to treat AIDS patients) and some anticancer drugs, have been isolated from sea organisms. Synthetic medicines such as ziconotide, a compound isolated from the venom of cone snails, are in clinical trials. Table 1 below lists marine-derived natural products in clinical and preclinical trials as of mid-2004.
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Diatoms like the ones shown here are an example of a silicon-encased marine algae.Image Courtesy: National Science Foundation |
Other natural products that can be purified from marine organisms are in use today as important nutritional supplements, industrial enzymes, cosmetics, sun screens, paint and plastic additives (as UV-blockers), natural pigments in fish food to add color to aquacultured species, and pesticides. For example, the carotenoids (orange-color pigments) astaxanthin, zeaxanthin, and lutein have high value and are being purified from microalgae and bacteria for use as anti-oxidants, anti-inflammatory agents, and as natural pigments for fish feed. Purification of these high-value carotenoid pigments is a growing marine biotechnology industry in Hawaii. Marine algae are also the source of two nutritional fatty acid supplements for infant formula. Some fatty acids are important for brain and eye development in fetuses and cardiovascular health in adults. These occur naturally in breast milk, but they have not been added to infant formula until recently.
The ocean’s unexplored biodiversity is threatened by increased human use, climate change, environmental pollution, overharvesting, and increased collection as scientists search for new natural products. Scientists fear that some species producing the most beneficial compounds will become extinct before the full potential of these compounds can be realized. Finding a sufficiently large or renewable source of a potential pharmaceutical or bioactive compound is a major hurdle in the development of novel marine bioproducts. Many of the potentially important compounds will come from rare species with low biomass, slow reproductive rates, and a limited geographic distribution. Furthermore, because many of the invertebrate species that may be important sources of interesting compounds have little to no value in the fishing industry, countries have not developed management strategies to prevent overharvesting of these species.
Recent advances in marine biotechnology and microbiology are helping scientists overcome many of the challenges involved in discovering useful bioactive compounds and bringing new marine natural products to market. Molecular genetic techniques, including the polymerase chain reaction and genomic sequencing, are being used to help researchers identify the genetic sequences involved in the production of natural products with interesting activities, as well as overcome some of the challenges of producing large enough quantities of an interesting compound.
The activities in this section of the curriculum are related to the search for biologically active compounds from marine organisms. Activities range from identifying products containing marine-derived compounds to testing for antibacterial properties of seaweed. Individual activities can be selected to complement classroom plans in biology, chemistry, or marine science classes, or the unit can be used as a whole.
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Table 1. Update: Ziconotide was approved as a drug by the FDA on December 30, 2004.Source: Data from David S. Newman, National Cancer Institute, Natural Products Division, Frederick, MD. |
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Bradley, David. 2003. Marine bugs make drugs. Reactive Reports Chemistry Web Magazine Issue #30. http://www.reactivereports.com/30/30_4.html. Accessed July 2009. Bruckner, A.W. 2002. Life Saving Products from Coral Reefs. Issues in Science and Technology online. http://www.issues.org/18.3/p_bruckner.html. Accessed July 2009. Feling, R.H., G. O. Buchanan, T. J. Mincer, C. A. Kauffman, P. R. Jensen, and W. Fenical. 2003. Salinosporamide A: a highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus salinospora. Angewandte Chemie International Edition, English, 42(3):355–357. Mincer, T. J., P. R. Jensen, C. A. Kauffman, and W. Fenical. 2002. Widespread and persistent populations of a major new marine Actinomycete taxon in ocean sediments. Applied and Environmental Microbiology. 68(10):5005–5011. National Institutes of Health. 2005. The Nation’s Progress in Cancer Research Annual Report: Ocean is a Treasure Trove of Possible Anticancer Compounds. http://www.cancer.gov/nci-annual-report/1.html . Accessed July 2009. |
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