The Potential Behind Our Investment Marine biotechnology has the potential to address societal problems that range from cancer and arthritis to seafood pathogens and environmental pollution. How is this possible? The answer rises from the marriage of natural resources with the tools of modern biology. The dramatic scientific and technological advances of the past two decades are making it feasible to explore and manipulate the diverse, novel, and largely unknown species of our seas. Below, we describe the factors compelling us to bring marine species into our laboratories and to take the tools of modern biology out to the seas.

The new tools of biotechnology not only are helping us discover useful compounds from marine life, but they also are making it possible to use bioactive compounds in a sustainable fashion.

Untapped Biodiversity

Microscopic plants and animals inhabit all regions of our oceans — from hospitable tropical waters to hydrothermal deep-sea vents and from frigid polar seas to super-pressurized ocean floors. Our oceans — the earth's greatest havens of biodiversity — are home to 34 of the 36 phyla of life. In contrast, only 17 phyla live on land.
	Photo: California Sea Grant

The adaptations made by organisms to the vastly different habitats in marine environments have resulted in highly diverse characteristics among marine species. Their biological and physiological characteristics can differ greatly from terrestrial species. These include novel protein structures, metabolic pathways, reproductive systems, and sensory and defense mechanisms. It is expected that these unique features bear unknown chemicals and compounds that will be useful in a wide variety of products and applications. The unsurpassed biological and chemical diversity of the oceans is one reason behind high expectations for unique molecules; another is the density of life in the oceans. For instance, in coral reefs of the Indo-Pacific Ocean as many as 1000 species of macroscopic plants and animals exist per square meter. Even more astounding are microorganisms— the major source of biodiversity in the oceans. One milliliter of ordinary seawater contains 1 million microorganisms. Not only do bacteria and fungi live in the water itself, they live on the surfaces of plants and animals, and in deep-sea sediments. Even the internal spaces of plants and animals are colonized by microorganisms as part of complex adaptations for survival.

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Wide-ranging Potential

Because species biodiversity translates into chemical and biological diversity, investigations of marine life are likely to yield numerous chemicals with uses in medicine, environmental remediation, agriculture, and industry.

Photo: New Jersey Sea Grant

 

Already, the species in coral ecosystems have proven to be valuable sources for new products. Bioactive compounds from such organisms are being used in skin-care treatments, bone grafting material, and insecticides. Some of the most exciting recent developments are pharmaceuticals now in clinical trials for cancer, microbial infections, and arthritis.

The possibility of discovering new compounds goes far beyond coral reefs. In fact, the major source of biodiversity in the oceans are microorganisms. The likelihood is high that a large pool of bioactive molecules is affiliated with these microbial populations.

Historically, natural chemical constituents or products of terrestrial organisms have been used to treat human infections and diseases. The scientific community believes that a systematic investigation of marine microorganisms not only will yield new pharmaceuticals, but also new products for environmental remediation, seafood safety, and agriculture and industry.

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Challenges on the Horizon

Although the benefits from marine biotechnology promise to be immense, several factors have inhibited progress. Challenges include the cost and availability of exploratory equipment, the state of scientific methodologies, and the natural supply of marine organisms.

 

• Exploration

The sheer cost of marine exploration and collection is a fundamental challenge to the emerging field of marine biotechnology. Most exploration has been confined to habitats that are accessible with scuba gear, in other words, to areas within 40 meters of the ocean's surface. However, new and improved submersible vehicles are being developed that can go farther and deeper into the oceans. The National Research Council has recommended applying tools and sensors designed for space exploration and diagnostic medicine to the discovery of marine resources (source: Marine Biotechnology in the Twenty-first Century: Problems, Promise, and Products).

• Cultivation

A second factor inhibiting product development is the inability to culture marine microbes. Research suggests that greater than 99% of the total marine microbial species cannot be cultured with commonly used methods. Even with new automated culturing methods that have isolated and cultured significantly more cells from coastal seawater, the vast majority of marine microorganisms remain unculturable. Hence, in 2002, the National Research Council noted that creative solutions for the identification, culture, and analysis of uncultured marine microorganisms is a critical need (source: Marine Biotechnology in the Twenty-first Century: Problems, Promise, and Products).

• Supply

The ability to retrieve a sustained, reliable harvest of marine organisms while protecting marine ecology is of paramount importance. Frequently, organisms produce the chemicals of interest in amounts too minute for the completion of research. Harvesting of organisms in the amounts necessary to complete research and development would endanger their existence and the surrounding ecological balance.

To address these last two challenges, scientists are looking to techniques and developments in biotechnology.

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Answering Challenges with Biotechnology

Molecular approaches offer solutions to the limited supply of natural products, giving scientists the potentially to clone genes involved in the production of desired chemicals. Molecular tools also provide a means of discovering new sources of molecular diversity through the identification of the genes and biosynthetic pathways of unculturable microorganisms.

Photo: New Jersey Sea Grant

The tools of biotechnology include genomics, DNA microarrays, and proteomics, all relatively new and evolving ways of learning about and using organisms. Below we describe their possible applications in marine environments.

• Genomics

The science genomics provides a new basis for understanding an organism's physiological processes and the responses it makes to environmental changes. It enables us to learn which stimuli cause an organism to synthesize a product that could benefit humans. In addition, the ability to determine an organism's genomic structure has increased speed and sensitivity in addressing specific questions. For instance, researchers can better determine which bacterial pathogens might be potential candidates for vaccines. Genomics also can reveal which genes can be targeted for drug therapy. How can genomics help us use marine resources? Genomic and bioinformatic methods present a new way to study uncultured microorganisms. As stated earlier, microbial life likely contain a large pool of potentially bioactive molecules, but because as much as 99% of these bacteria are not culturable by standard methods, the chemicals from them have been inaccessible. With current technology, the DNA in such environments can be surveyed and sequenced. Using bioinformatic analysis scientists then can pinpoint genes with chemical potential. Cloning and expression of these selected genes from uncultured bacteria will likely lead to the discovery of novel bioactive molecules. Although relatively new to the marine environment, these methods have been used successfully in looking for antimicrobial proteins from uncultured soil bacteria.

Definition: Genomics is the sequencing, annotating, and interpreting of information contained within the genome of an organism. Genome sequencing of microorganisms, the majority of earliest work in genomics, has led to a better understanding of the biology of these organisms. For instance, unsuspected metabolic pathways were revealed in well-characterized bacteria through genomics. Today, technological breakthroughs in automated DNA sequencing and bioinformatics make it possible to sequence and annotate larger and more complex genomes rapidly.

• DNA Microarrays

Microarray technology is one of the most recent and important experimental breakthroughs in molecular biology. This new tool is used for analyzing an organism's genome and for assessing its responses to specific environmental changes. A qualitative leap above previous tools, microarrays enable scientists to analyze the expression of many genes in a single experiment quickly and efficiently. Microarrays have great potential as diagnostic tools in environmental monitoring, bioremediation, and drug discovery. This is because microarrays are particularly useful in examining the gene expression patterns of a model organism in response to stimuli. (Gene expression is a highly complex process that allows a cell to respond dynamically to environmental stimuli and to its own changing needs.) For instance, a test sample could represent genes coding for proteins likely to be expressed before and after the introduction of a stress, such as pollution. In such a case, it could be determined which genes are expressed as a result of the environmental stress. It also is possible to learn the genomic differences between two organisms from microarrays, particularly if a complete reference genome is available for comparison. The total genomic DNA of the second organism is used as the test sample for hybridization to the genome microarray of the first organism. With these data, scientists can rapidly determine the genes found on the reference genome, as well as the genes that are the same in the two organisms.

Definition: A new tool for analyzing gene expression, a microarray consists of a small membrane or glass slide containing minute samples of many genes arranged in an orderly pattern. These genes are analyzed through a process based on hybridization probing, using fluorescently labeled nucleic acid molecules as "mobile probes" to identify complementary molecules that base-pair with one another. The florescent probes (DNA, cDNA, or messenger RNA) find the immobilized target DNA; they then lock together, or hybridize. A scanner examines the slide by exciting the fluorescent tags with a laser and then creating a digital image of the array. The pattern of fluorescence is analyzed by a computer.

Source: The Microarrays Science Primer, provided by the National Center for Biotechnology Information (NCBI), was the primary source for this information on microarray technology. For a more comprehensive description of microarrays, see NCBI's Science Primer

A relatively new science, proteomics links genetics with physiology by providing clues to the function of genes encoding certain proteins, as well as to the function of the proteins they encode. As proteomic methods evolve, it is hoped that by combining them with the investigative techniques of classic microbiology and genomics, scientists will understand how organisms react and adapt to their changing environments — from the level of individual genes to the chemicals that they express. With this understanding scientists will be able to maximize production of important bioactive compounds from marine organisms that may impact pharmaceutical development and health care.

Definition: Through proteomics, an extension of the Human Genome Project, the proteins specified by the genome of an organism are characterized according to their function.

Credit Top Mast Photo: Florida Sea Grant