2001 Workshop Abstracts: Biomedical Applications



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Marine Biotechnology in the Twenty-First Century: Problems, Promise, and Products 2001 Workshop Abstracts: Biomedical Applications

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Marine Biotechnology in the Twenty-First Century: Problems, Promise, and Products This page in the original is blank.

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Marine Biotechnology in the Twenty-First Century: Problems, Promise, and Products Keynote Address FULFILLING THE PROMISE OF MARINE BIOTECHNOLOGY Dr. Rita Colwell Director, National Science Foundation Marine biotechnology is a field with great potential, but with a distance yet to run. Over the past 30 years, we have seen incredible growth in many facets of genetics. Genetic information is used to produce new pharmaceutical products, disease-resistant plants, and modified microorganisms for industrial and environmental use. Marine microbiology, however, in spite of some impressive discoveries, has essentially been left behind. These discoveries include hundreds of marine microorganisms and invertebrates with the potential of producing new pharmaceuticals, cosmetics, or nutraceuticals; new ways to raise fish, molluscs, crustaceans, and algae in aquaculture; and new ways to sense marine environmental changes. Yet, marine biotechnology is still a promise to be fulfilled while other areas of biotechnology have flourished both in science and in the marketplace. The biotechnology pie can be divided into four major market segments: biomedical, agricultural, industrial, and environmental. Biomedical biotechnology is the most visible and has been since the introduction of a monoclonal antibody-based diagnostic test kit in 1981. This kit was the

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Marine Biotechnology in the Twenty-First Century: Problems, Promise, and Products first biomedical, biotechnological commercial product approved by the U.S. Food and Drug Administration (FDA). The following year, Genentech’s recombinant human insulin (Rhinsulin; Humulin) was approved in the United States and is now used daily by more than 4 million people with diabetes around the world. From 1982 to 1989, only 18 biotechnology-based drugs were approved by the FDA; then the numbers rapidly increased with 22 new biotechnology drugs accepted by FDA in 1998 and in 1999. Thirty-one new drugs and vaccines were approved in the year 2000. The human population is reaping the benefits from this biotechnology explosion; there are now new drugs to treat herpes, rheumatoid arthritis, rattlesnake bites, diabetes, and cancers. The agricultural sector has also experienced tremendous progress since the market introduction of the genetically engineered Flavr Savr tomato in 1994. Canola, corn, cotton, peanuts, potatoes, soybeans, sunflowers, and tomatoes are all more productive due to biotechnology. Many of these innovations are targeted at producing plants that are more resistant to insects and fungal diseases. Though not yet as prolific as biomedical or agricultural biotechnology, industrial and environmental biotechnologies aim to minimize pollution and enhance materials and energy use, while maximizing production of recyclable or biodegradable products. To do this, microorganisms are bioengineered to degrade hazardous wastes, including chlorinated solvents, detergents, creosote, pentachlorophenol, and PCBs. Plants are induced to remediate organic and inorganic pollutants, including radionuclides. Enzymes that can function at extreme pH or temperature are being isolated and employed. Through recent advances in genomic mapping, it is now known that humans, apes, and fruit flies are all closely related. Current science suggests that a minor difference in gene expression can make a major difference in structure, function, or longevity. As biotechnology adjusts gene expression to develop new products, this must be achieved with an eye toward scientific responsibility and good stewardship for the earth and humanity. When researchers leap into the unknown, they must use science as both a propellant and a safety net to predict where discoveries may lead and prevent adverse outcomes. Marine biotechnology encompasses pharmaceutical, agricultural, industrial, and environmental applications. Although marine biotechnology is poised on the edge of a period of tremendous potential—potential for

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Marine Biotechnology in the Twenty-First Century: Problems, Promise, and Products discovery, potential for development, potential for design—the field is still in the realm of the future. In 1985, I wrote, “There are several reasons for the lack of development in the area of marine pharmaceuticals. . . .” and then cited the difficulties of retrieving a sustained, reliable harvest of marine organisms; insufficient quantities of material to allow for study completion; and difficulties culturing marine organisms in the lab. Unfortunately, the same holds true today. In the 1970s, recombinant DNA techniques were mastered, and unique microorganisms living in ocean-floor hydrothermal vents were discovered. It became clear that the application of genetic engineering to all forms of marine life formed a synthesis. The field of marine biotechnology was on the map and included production of commercially and medically important chemicals from algae and marine invertebrates; production of transgenic fish, crustaceans, and molluscs for food; and genetically engineered medicines and vaccines. Seaweeds are an abundant source of food and food products, including carrageenan, vitamins, nutrients, and animal-feed additives. Chitin and chitosan, the polysaccharides derived from the exoskeletons of marine crustaceans, are used as gelling agents to control ice formation in frozen foods, as antifungal agents for agriculture, and as sutures and poultices in medical applications. The discovery of many toxic molecules in ocean creatures indicated that the ocean was a likely source of pharmaceuticals. Despite nearly 40 years of research, there are only a few approved pharmaceuticals derived from marine organisms. These pharmaceuticals include materials originally isolated from marine sponges (the antiviral acyclovir, AZT, and the anticancer drug Ara-C) and cephalosporins, the antibiotics originally isolated from a pseudomarine fungus. Fifteen other compounds isolated from marine organisms, many of which were discovered with the assistance of the National Cancer Institute’s Natural Products Branch, are in clinical trials or earlier stages of drug development. One anti-inflammatory substance, a partially purified pseudopterosin extracted from the Caribbean sea whip, the soft coral Pseudopterogorgonia elisabethae, has been licensed for use in skin-care products. Hydroxyapatite, from marine coral, has FDA approval to be implanted into fractures or voids of human bones to aid in regrowth and repair. Horseshoe crab blood provides the basis of the limulus amebocyte lysate (LAL) test, which can test in less than an hour for endotoxin contamination in

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Marine Biotechnology in the Twenty-First Century: Problems, Promise, and Products medicines and medical appliances. Society needs many more of these quick-acting substances on which to base tests for human toxins and pathogens. As I forecasted in 1983, the merger of genetic engineering with marine science created an opportunity for ocean research to provide products to improve humanity. Despite the advances in the identification and screening of organisms for biologically active compounds, production of sufficient amounts of the compounds depends on a number of factors. One is the ability to chemically synthesize the compound. Another is the ability to raise the organism in culture. A third is the ability to harvest the organism from its natural environment. All three of these issues can be seen in relation to the marine invertebrate Bugula neritina. For example, it has long been hypothesized that B. neritina, a brown bryozoan animal, is not the true source of the antitumor compound bryostatin. Recent data from Scripps Oceanographic Institute indicated that the bacterium Candidatus endobugula sertula, which lives inside B. neritina, may be the agent producing this drug. If the gene is isolated from the bacterium, then biotechnology may provide a means for large-scale production of bryostatin for cancer treatment. Currently, modest production of bryostatin is achieved by limited mariculture. Integrated mariculture systems allow land-based production of valuable bivalves, including Mercenaria mercenaria, the hard clam, a seafood of choice for many of us. Providing the proper environmental conditions— pH, temperature, oxygen, lack of toxins, or pollutants—while removing waste products like ammonia and organic and inorganic carbon, is a challenge that engineers are solving for improved productivity in aquaculture facilities. The challenges in developing mariculture are not solely for biologists. Genetic engineering methods allowed cloning of genes from coelenterates to create products for cell biology research. Green fluorescent protein is a useful marker for tracking calcium in cells. The process has been “humanized” and cloned into mammalian expression vector systems. Researchers in the Extreme 2001 Expedition, a deep-sea investigation, announced in Fall 2001 that they succeeded in conducting the first-ever DNA sequencing experiments at sea. Genomes of the inhabitants of superhot, hydrothermal vents almost 2 miles deep in the Pacific Ocean were sequenced. These organisms may yield new products ranging from pharmaceuticals to heat-stable, pressure-resistant enzymes for food processing or hazardous-waste cleanup.

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Marine Biotechnology in the Twenty-First Century: Problems, Promise, and Products To utilize the resources at hand best for achieving results that marine biotechnology promises, government must increase its involvement in marine biotechnological research. In the United States, for example, marine biotechnological research is funded mainly through the National Science Foundation (NSF), the National Oceanic and Atmospheric Administration (NOAA), and the Office of Naval Research (ONR). Smaller amounts of funding are also provided by the National Institutes of Health through the National Cancer Institute (NCI). NSF’s 1999 marine biotechnology funding reached $12 million. NOAA’s portion was $10 million (about $8 million of which is earmarked for the National Sea Grant College Program), and ONR awarded $5.6 million for marine-related research. For the 2002-2007 budgets, NSF, NOAA, and ONR each will request annual increases of $10 million for marine biotechnology. They also will request an additional $3 million per year for outreach and education. The NSF, ONR, NCI, NOAA, and U.S. Department of the Interior, under the aegis of the National Science and Technology Interagency Biotechnology Research Working Group, Marine Biotechnology Task Force, have proposed a $50 million interagency initiative. This initiative, called COMPASS (Coordinated Marine Programs to Assess and Sustain the Sea), will be an interagency program to advance marine biotechnology, coordinate federal research and outreach in marine biotechnology, and address gaps in federal marine biotechnology funding. At the NSF’s Biological Oceanography Program workshop “Ecological Genomics: The Application of Genomic Sciences to Understanding the Structure and Function of Marine Ecosystems,” it was suggested that a Virtual Marine Genome Center be established to contract out high-throughput genomics and to aid in the selection of organisms for sequencing. One of the requirements for the growth of marine biotechnological research is the increased use of genomics to learn more about the oceanic environment. More studies of ecology, symbiosis, and marine pathogens (such as my research group’s continuing work on Vibrio cholerae), and production of biosensors must be performed. As more is learned, this scientific knowledge must be transferred to inform and educate the public, who are the people that fund and support our work. The public must understand biotechnology and not fear it. Eighteen years ago, I thought that the marine biotechnology revolution was just about in reach. From the amount of research done in the field since then and the numbers of discoveries, I would say that, indeed, it was.

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Marine Biotechnology in the Twenty-First Century: Problems, Promise, and Products Nevertheless, from the small number of new products that exist today, I would have to say, the results of the revolution are unrealized. That is our challenge! Today we are so much closer to the goal of realizing the sea’s true potential, but we need coordinated national and international efforts and infusions of funds. Unlike 18 years ago, the technology has matured. I urge the participants in this workshop to put our combined knowledge to use and help society move forward to solve health and food-supply problems with the tools and research results of marine biotechnology.