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Dr. Colwell's Remarks


"Marine Biotechnology: A Confluence of Promise"

Dr. Rita R. Colwell
National Science Foundation
Marine Biotechnology Conference 2003 Keynote Lecture
Chiba, Japan

September 22, 2003

See also slide presentation.

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Good morning to all participants. I am honored to deliver this special lecture to the Marine Biotechnology Conference 2003. It is a special pleasure to be able to greet so many old friends from the marine biotechnology community. This conference represents nations from around the world and is an eloquent testimony to the international strength of our discipline. I would also like to acknowledge conference conveners and the organizing committee, both national and international.

We are very fortunate to have Japan as our host country this year. Through its support for marine biotechnology over the past two decades, Japan has shown a true vision for the future of the discipline. Japan hosted the first international marine biotechnology conference in 1989, nearly 15 years ago, and it is a pleasure for us to return here. Certainly, Japan's frontier research on deep-sea organisms, both micro and macro, and its pioneering work on the commercialization of marine biotechnology products, are achievements to celebrate. Japan will also participate in the Integrated Ocean Drilling Program, which will explore our planet's crust beneath the oceans, with potential for revealing clues to the origin of life.

[title slide on]
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I have titled my talk "Marine Biotechnology: A Confluence of Promise." As practitioners of marine biotechnology, we share a belief in the sea as a living treasure house—some secrets known, some yet to be discovered--for human beings and our environment. Henry Beston, the modern American essayist, must have had creatures of the sea in mind when he wrote, "In a world older and more complete than ours, they move finished and complete." This is the most basic rationale for investigating marine life with the most sophisticated tools available: these creatures inhabited our ancestral world, where all life began.

Two decades ago, I wrote in the journal Science about the "immense potential of biotechnology for the marine sciences." I predicted then that genetic engineering, in particular, held extraordinary promise for our field—in fact, I highlighted genetic engineering as "the greatest opportunity of all."

[new convergence zone image with words: Discovery foments in the "hyphenated" zones of convergence.]
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Twenty years later, marine biotechnology is poised to benefit even more from confluences in fundamental research. Across all of science today, much of the excitement of discovery ignites at the interfaces of disciplines. The sea itself provides a metaphor for this, where water masses of different temperatures converge; in these zones, gyres form, polynyas appear, upwelling occurs, and nutrients collect at the interfaces.

Of course, convergence zones may appear, shift and disappear, but they are often where nutrients mass and where fish and seabirds up the food chain concentrate to feast. Just so are the interfaces between physical science, engineering and biology, and now the social sciences: discovery foments in these "hyphenated" zones. Such interfaces have tremendous potential to accelerate progress in marine biotechnology.

[word slide with the themes]
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This slide sets forth the themes of my talk. Our own evolutionary origin from the sea has long stimulated expectations of benefits from marine organisms. Today, however, we can expect even greater genetic revelations from the sea than we might have imagined twenty years ago. Marine biotechnology is now truly poised to reach its full potential.

New discoveries across the spectrum of science and engineering are portents of progress for our discipline, and I will survey some of these.

Foremost is the revolution that has seized microbiology in the past decade or so, including great strides in the ability to identify and sequence microbial life, new appreciation for the roles marine microorganisms play in biogeochemical cycles, and the growing realization that marine microbial symbionts produce many bioactive compounds.

Next I will discuss how broader advances in interdisciplinary science—such as information technology, nanotechnology and biocomplexity—also furnish major new capabilities for our field. These capabilities emerge from the intensifying convergence of disciplines across all of science and engineering—a phenomenon very evident from my vantagepoint as director of the National Science Foundation. In fact, NSF has marked these areas of confluence for special investment, in recognition of their potential to accelerate progress throughout the scientific enterprise.

New knowledge generated with these capabilities, in turn, gives us a more sophisticated way to conserve marine biodiversity; I will discuss this in conjunction with new models developed to establish equitable partnerships in bioprospecting with developing nations.

[Great Barrier Reef: Great Spawn]
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Nothing represents the creative wellspring of the sea like the spawn of the Great Barrier Reef. In the largest annual reproductive event on earth, when the temperature is right and the moon is just past full, more than 150 species of coral release eggs and sperm at once. I like to imagine that, if this great chemical explosion—which resembles an undersea snowstorm—could be transformed into music, it would sound as magnificent and complex as Beethoven's Ninth Symphony.

[nacre inset with spiral background]
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The diverse genetic riches of the ocean—embracing all but two of life's 36 phyla—suggest the broad potential to produce pharmaceuticals, model organisms for research in many fields, and many benefits for agriculture, the environment, bioprocessing and aquaculture. This image symbolizes some of that promise; nacre, or mother-of-pearl, is renowned for its strength and flexibility. Chemists supported by the National Science Foundation have taken natural nacre as their model to create a lightweight, artificial material, shown in the inset picture. Fashioned at the nanoscale, this material could have ultimate application in aircraft and artificial bones.

[Table 1 from NRC report]
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This table from a recent US National Research Council report gives some examples of marine bioproducts now on the market. They range from antiviral and anticancer drugs to a nutritional supplement and a cosmetic ingredient. They come from sponges, jellyfish, bacteria and algae.

The medicinal harvest from the sea is really no surprise; our evolutionary connection is a compelling reason to seek beneficial products, pathways and clues to our own makeup from the sea.

Vestiges of our origins include the composition of our blood, the rudimentary gills of early human development, the natural swimming response of babies in water. We turn to the sea not only for medical compounds but also for clues to blood pressure control and to the transfer of carbon dioxide in the lungs.

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Can the sea's secrets shed special light on the dynamics of diseases that affect the brain, from Alzheimer's to Parkinson's to depression? My own past research on oysters with Ron Weiner of the University of Maryland showed that oyster larvae were attracted to settle on surfaces already colonized by bacterial films. Eventually, it was discovered that one of the chemicals produced by those bacteria is L-DOPA—the same chemical used to treat Parkinson's disease. Another example: bivalves and gastropods will metamorphose in the presence of gamma-aminobutyric acid—an amino acid almost identical to one of the important neurotransmitters in the human brain.

[deep-sea vent]
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Fundamental research on the evolution of life in the sea is a foundation for progress in marine biotechnology. Hydrothermal vent systems are being investigated as the cradle of life. This vent, called the Lost City, rises 18 stories tall in the Mid-Atlantic Ocean—and we have just learned that it was built without volcanism. Instead, the Lost City is heated through a chemical reaction between seawater and the Earth's mantle beneath. Earlier in our planet's history, before crust had covered over the mantle, many such sites might have pocked the early seafloor. Similar vents, if found, might turn out to be very old, perhaps having pumped out heat, minerals and organic compounds for millions of years, and thus serving as incubators of early life.

[sponge with dye]
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The sponges—shown to be especially rich in interesting compounds—may well resemble the first animals on the evolutionary tree. A luminescent dye assists visibility of this sponge's pumping ability (and I extend special thanks to Mark Shelley and the PBS series "The Shape of Life" for lending this photo).

[sea squirt-adult]
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The lowly sea squirt, it turns out, is the first creature to have evolved an immune system resembling that of a vertebrate and its embryo is similar to a human's.

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The upper photo shows the notochord or precursor backbone of Ciona, the sea squirt, and the diagram at the bottom shows its evolutionary relationship with us.

[sea squirt and human: genomes compared]
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Last December the sequencing of the sea squirt's genome was announced. Here, on the Joint Genome Institute's website, the genome is compared with those of a human, worm, fly, yeast, and that of Arabidopsis. The sea squirt serves as a model organism to study how more complex life evolved.

[giant squid axon: potassium channel diagrams]
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The giant axon in another sea creature, the squid, gave us the classic early insight into the relationship between permeability of membranes and neuron signals. No terrestrial animals have such neurons of this size. The potassium channels, sketched here, control the nerve firing, and are not only a basic mechanism of life but also play roles in heart arrhythmias and seizures. Again, our own marine ancestry makes us regard marine diversity with a fresh eye—viewing animals as models, as well as sources of compounds that control the developmental stages of life.

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We know—as a recent U.S. National Research Council report puts it—that "many aquatic species have been waging 'chemical warfare' with each other for millennia..." A central means is neurotoxin. Tetrodotoxin, one of the most potent neurotoxins known, is present in the pufferfish and has become a critical toxin in neuropharmacology and neurophysiology research.

Here are the beautiful cone snails, the group of 500 species that are the source of an incredible array of toxins.

As Baldomera Olivera of the University of Utah says, these animals could be among the world's most successful pharmacologists, potentially producing tens of thousands of compounds—peptide toxins—with pharmacological activity. Each toxin targets a specific function in the cell. One cone shell's venom has inspired a synthetic molecule that shows promise to control chronic pain in patients resistant to opiates.

[quote on background image]
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These discoveries give but a flavor of the promise and products of marine biotechnology. Indeed, when I published my Science paper twenty years ago, I thought the marine biotechnology revolution was just about in reach. However, while medical biotechnology has accelerated, marine biotechnology, despite some successes, seems to have experienced a long lag phase—that quiet interval after inoculation, just before exponential growth takes off. Despite nearly 40 years of research, only a few pharmaceuticals derived from marine organisms have been approved.

To be sure, marine biotechnology remains an emerging discipline. As noted in a recent report by the U.S. National Research Council, "Fundamental knowledge is still lacking in areas that are pivotal to the commercialization of biomedical products and to the commercial application of biotechnology to solve marine environmental problems..." Familiar but still valid reasons for lack of progress include the difficulty of sustaining harvest from marine organisms, the insufficient amounts of material for study and trials, and the difficulty of culturing organisms in the laboratory.

[image-sea life collage]
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I believe that now, marine biotechnology is poised to undergo a sea change—because of the confluence of progress in fundamental research. A major milestone has been the discovery of enormous biodiversity in the world oceans. More than 300,000 species of plants and animals have been identified in the sea, and just a single square meter of coral reef may support 100 species of organisms. Twelve thousand new chemicals have been found that are produced by ocean life.

Just a milliliter of seawater harbors millions of microorganisms, and huge populations of viruses have been discovered, whose particles in seawater outnumber microbial cells ten-fold.

We have watched the discovery of an entire branch of life—the archaea, comprising 20-30% of microbes in the sea—which has revolutionized our understanding of the Tree of Life. And while past bioprospecting has focused on the tropics, we have begun to realize that there is a tremendous diversity of life hidden in the deep sea and at high latitudes. At the same time, the scientific technologies are maturing that will chart this life and extract its benefits.

[word slide: biocomplexity, information technology and nanotechnology]
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Among the areas of confluence in science and engineering today, three have special potential for marine biotechnology. These converging areas—each the focus of special investment by the National Science Foundation—are biocomplexity, information technology, and nanotechnology.

[biocomplexity spiral]
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The first, biocomplexity, is a perspective on the biosciences that spans scales and disciplines. This is a new framework for charting the relationships between life and its environment. Here I use the form of a spiral, so evocative of life at every level, to underscore that understanding demands observing at multiple scales, from the nanoscale to the global. The spiral of complexity begins to unfurl at the most minute scale of the atom and curves up through successive levels of life. With the perspective of biocomplexity, disciplinary worlds, formerly discrete, intersect to form fuller, more nuanced viewpoints. The spiral curves both ways—outward, integrating the levels of life, and inward, back toward the center.

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Biocomplexity helps us to appreciate how the trillions of microorganisms in the ocean—playing key roles in cycles of elements like carbon and nitrogen—are driving processes on grand scales, including helping the oceans to orchestrate the earth's climate.

The complex relationship between an organism and its environment, and the necessity to look across scales, is exemplified by the coccolithophores, the one-celled plants. Coccolithophores play a multitude of roles; they affect cloud formation, carbon cycling, and climate. When they die, they produce dimethyl sulfide (DMS)--particles that eventually become nucleii for cloud condensation. While alive, these plants utilize carbon in seawater, with the result that the ocean draws more carbon from the air. Still another impact: blooms of some coccolithophores can triple the amount of light reflected into space by surface water. A truly rich tapestry of complexity surrounds this phytoplankton.

[bacteria in background, chart in foreground]
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Another example of how a very small organism can have a major impact on the environment is the recent discovery, by Ed Delong and his team at the Monterey Bay Aquarium Research Institute, of a new photosystem in ocean microorganisms. By creating a library of DNA from marine microorganisms, the group discovered that a photoprotein, a type of rhodopsin previously found only in Archaea, exists in bacteria as well. Furthermore, they showed that bacteria containing this energy-generating, light-absorbing pigment are almost ubiquitous in the world's oceans.

Another remarkable feature: genetic variants of these bacteria have slightly different pigment molecules that seem "tuned" to absorb light of different wavelengths, matching the type of light penetrating to different depths. These bacteria may play a role in the carbon cycle and hence should be considered in global climate models. Here again we see how biocomplexity's perspective, arching across scales, helps to frame the big picture of marine organisms in their environment.

[generic infotech pic]
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Another area of science and engineering confluence is information technology—IT is an important NSF focus as well—which is already driving progress in marine biotechnology. IT has transformed the very conduct of research, helping us to fathom complexity, form new collaborations and do new kinds of science. It lets us share and mine massive data sets and accelerates the convergence of disciplines.

[SAR 11]
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Information technology undergirds genomics. Take the case of SAR-11, a group of microorganisms studied by Steve Giovannoni of Oregon State University and Craig Carlson at the University of California-Santa Barbara. They are working together at the NSF Microbial Observatory in Bermuda.

Although the SAR-11 group has biogeochemical significance on a global scale—estimates are that it may be responsible for 10% of nutrient recycling on Earth—SAR-11 was not successfully cultivated despite more than a decade of attempts. Now, high-throughput technology has enabled cultivation, complete sequencing of the genome, and pinpointing of the SAR-11 genes that play key roles in earth processes.

Meanwhile, Craig Venter and his team are finding thousands of new species in the Sargasso Sea and elsewhere in the Atlantic Ocean alone.

[remote observatory]
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IT also lets us envision ocean studies on another plane--ambitious and integrated. New facilities will allow unlimited observations of the sea, including the deep sea, enabling the study of processes from earthquakes to ecosystem interactions to climate change. At this envisioned seafloor observatory, instruments will be turned on and off remotely, and monitoring will be able to trigger rapid deployment of a submersible in response to climate or geologic events.

Also part of this vision is the use of portable observatories, based around a system of large, instrumented buoys. They will collect important data in remote areas such as the Southern Ocean.

[Mark Wells: HAB with liposome inset]
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A third capability of confluence for our field is nanotechnology, the frontier dimension where the living and the non-living meet. Nanotech—to take one example—offers insight into the unique role of iron in regulating marine ecosystems. Iron limits plankton production, and iron may be a critical element in harmful algal blooms. Now, a nanodevice may meet the need to measure in situ the fraction of iron that is available for phytoplankton to use.

NSF-funded investigator Mark Wells of the University of Maine, and his team, have developed such a device based on liposomes, small spheres 100 nanometers in diameter that can serve as delivery vehicles for substances—in this case, a molecule designed to bind iron. These devices, Wells says, "open the way to applying nanotechnology to create a new breed of iron 'biosensors'" in seawater.

The nano-size of the device greatly increases the surface area of a membrane that can interact with the solution around it. Also, smaller spheres mean better diffusion—increased efficiency that is important given the very low iron concentration in the ocean. These nano-devices ultimately could be used on remote vehicles or moorings below the sea surface to study how biosystems interact with their chemical environment.

[Sargasso Sea pic]
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Bio, info, nano—all have contributed to the revolution in microbiology over the past decade—itself one of the most potent portents for marine biotechnology. The 3.5 billion years of evolution representing the heritage of the prokaryote have generated a wealth of diversity to tap, as suggested by the image of bacterioplankton from the Sargasso Sea.

For marine biotechnology, in fact, one of the most intriguing confluences of all that has occurred in recent years is the growing evidence that it is marine microbial symbionts living within corals, sponges and tubeworms that are the "real chemists" producing many compounds of interest.

Yet the diversity of the microbial world—where so much biochemical variety resides—has been not only inaccessible but unknown because only an estimated 0.1% of microorganisms have been cultured. None of the others—some 99% of marine microorganisms—have been analyzed for their biochemical potential.

A true "sea change" is that ribosomal RNA—described as a kind of "universal bar code" by Ed Delong of the Monterey Bay Aquarium Research Institute--can be used to identify microorganisms without having to culture them. This is how he and his group discovered that bacteria contain rhodopsin.

[NSFPR 03-84]
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Just a month ago, as this NSF press release portrays, Science Magazine featured "Strain 121"—a microorganism that lives at 121 degrees C—the hottest existence known, in a black smoker on the Juan de Fuca ridge off the northwestern United States. Its discovery was reported by Derek Lovley and Kazem Kashefi of the University of Massachusetts-Amherst, and it was isolated by John Baross at the University of Washington.

I cannot help but look back to when I was a graduate student, when we were taught that the deepest parts of the ocean were devoid of life. Now, undersea vents are recognized as potential goldmines of genetic clues to how organisms handle environmental stresses, whether extremes in temperature, pH, salinity or oxygen.

[East Pacific Rise: map]
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Deep-sea vents have played a surprising role in my own research on Vibrio cholerae, the organism that causes the disease cholera, revealing another link between human health and the sea. Since Vibrio cholerae requires salt to grow, we have suggested that its ancestral home is the sea. The isolation of the genus Vibrio from deep-sea hydrothermal vents was first reported in 1981.

In 1999, during dives by the submersibles Alvin and Nautile, sulfide chimneys were collected from vents on the East Pacific Rise. Vibrio species isolated from the chimneys bore significant similarity to Vibrio cholerae, suggesting that it is indeed native to the deep sea.

[Norbert Wu: Antarctic sea floor community]
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At quite the opposite extreme, in Antarctic waters, Jim McClintock and Chuck Amsler of the University of Alabama-Birmingham and Bill Baker, University of South Florida, have studied the basic chemical ecology of marine invertebrates. As a sideline, they have also supplied extracts of Antarctic compounds to drug screening programs, several of which show activity against some forms of cancer. Antarctica's diverse marine biota clearly have potential to yield novel chemicals with pharmaceutical potential.

[pompeii worm and DNA sequence]
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Only in the past few years have we begun to employ the powerful new tool of genomics to identify "what's out there" -and microbiology has benefited perhaps more than any other field. In 2000, Shil Dassarma, with Leroy Hood, reported the complete sequence of an extreme halophile, containing more than one-third novel proteins. Late in 2001, scientists directed by University of Delaware marine biologist Craig Cary sequenced DNA at sea for the first time. Among creatures investigated was the one in the picture, the deep-sea pompeii worm covered with a fleece of bacteria, which themselves may possess heat-resistant enzymes.

We also know now that microorganisms have evolved by sharing their genomes to a startling extent. All of this has raised new questions: What influences the frequency and nature of lateral gene transfer? Most fundamentally, we are forced to rethink our concept of species at the microbial level.

[new Yellowstone pic]
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Here at a thermal spring in Yellowstone National Park, a team led by David Ward of Montana State University is indeed probing a new concept of species. They are exploring the mixed origin of genes in a genome—some inherited conventionally and others acquired through lateral transfer from organisms in the environment. The traditional concept of species falls short of being able to describe these communities of microorganisms.

[diagram of metagenomics approach]
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A new approach called metagenomics or ecological genomics encompasses the community rather than the species as the unit of study. The process begins by recovering large genomic fragments directly from microbial communities, such as those in the sea. We can sequence the complete suite of DNA, as represented in a sample, thereby revealing the proteins produced by microorganisms—without having to culture them.

The community genome provides a comprehensive picture of the gene functions distributed among individual members. All genes necessary to perform the diverse biogeochemical reactions that make up ecological community function should be represented. Although still in their infancy, these techniques will let us begin to plot the full spatial and temporal heterogeneity, and the complexity, of many microbial communities.

[bobtail squid]
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On quite another front, great strides have been made in recent years on "listening in" on bacterial communication. Sea creatures have revealed a mechanism of microbial communication that turns out to be of great medical interest. Here we see the beginning of the story—a bobtail squid from Hawaii, which exudes a ghostly blue glow on moonlit nights. The squid's secret is to ingest great quantities of luminescent bacteria, which glow inside the animal and cause its shadow to vanish—perfect camouflage.

The deeper secret is that whispers of communication animate this ingested community of glowing bacteria. This signaling among the bacteria takes place through chemical secretion. Only when enough chemical builds up—a threshold called quorum sensing, which is reached when a critical number of bacteria are present—do the bacteria light up, making the squid glow.

[signaling microbes]
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Bonnie Bassler of Princeton University and others have discovered that this bacterial communication governs a wide variety of bacterial pursuits. E. coli and many other bacteria responsible for human diseases use similar signaling; in fact, discovery of the "signaling gene" could lead the way to foiling drug-resistant bacteria. Here's a case in which the study of luminescence in marine bacteria—once considered "incredibly arcane, with no application at all"—produces a fundamental insight for human health.

[general biofilm illustration from Costerton]
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Fundamental new knowledge about bacterial communication has obvious implications for marine biotechnology. Biofilms are a case in point, and they are a focus of a National Science Foundation Engineering Research Center led by Bill Costerton.

Here is an artist's rendition of a biofilm built by bacteria—a film that protects the bacteria from antibiotics, antibodies, and white cells. This structure requires bacterial communication, including quorum sensing, to construct.

Biofilms may be behind two-thirds of infections--whether children's persistent ear infections, tooth decay, or problems with mechanical heart valves.

[red algae]
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This red alga, it turns out, produces molecules called furanones, which inhibit biofilm formation. They have been used to foil biofilm formation on boats, fishing nets, and contact lenses.

[experimental tubes with and without biofilms]
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The plastic tube treated with furanones—it's in the center—resists being covered with biofilm, unlike the untreated tubes on either side.

It is now proven that molecules called furanones-produced by red algae—inhibit biofilm formation.

[mice graph]
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Here is graph showing mice carrying an infection model for cystic fibrosis pneumonia. The mice represented by the red bars on the left received a saline solution. The mice represented by the yellow bars on the right were treated with furanones. Many of the latter were virtually cleared of the CF-associated infection. Clearly, compounds that protect marine animals from biofilms may also protect humans from some biofilm-associated infections.

[MarBEC home page: screen shot]
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Another NSF Engineering Research Center—you see its homepage here-- is the Marine Bioproducts Engineering Center in Hawaii. MarBEC is a partnership between the University of Hawaii and the University of California-Berkeley. The center's philosophy merges the intellectual with the pragmatic--speaking to one of our discipline's foremost concerns: how to develop the engineering technology and science base to produce high-value marine bioproducts commercially. MarBEC partners with such industries as chemicals, pharmaceuticals, advanced materials, food, feed, energy, environment, cosmetics, and aquaculture.

One of MarBEC's projects has been "the first attempt to assess the potential of archaea for the elaboration of small molecules of pharmaceutical interest."

Another project focuses on gene expression—that is, developing DNA microarrays—in deep-sea extremophiles. The goal is to find genes that govern novel biosynthetic pathways and the production of bioproducts, such as enzymes, biopolymers, biotherapeutics, and pharmaceuticals.

MarBEC researchers are creating a high-temperature and high-pressure bioreactor that may aid the discovery of obligate extremophiles--those that cannot naturally survive outside their extreme environment.

Elsewhere, there are also emerging technologies in the area of marine aquaculture. An example is the use of microbial-mediated removal of chemical waste, employed in recirculated, environmentally compatible mariculture. This is based on the use and engineering of beneficial microbial communities.

[quote with background]
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Many streams of knowledge—which I have termed confluences—are enriching the future of marine biotechnology. But one final confluence underlies and enables all the others: marine biotechnology cannot progress without marine conservation.

Our specialized knowledge brings with it the special responsibility to work to conserve the biotechnological riches of the sea and to sustain the marine environment. As I have outlined, we have just begun to map the microbiological riches of the ocean, and it would be a tragedy to destroy that which we have not yet even named, let alone understood.

[Nature cover, 2003]
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On a number of fronts, the prospect for sustaining ocean biodiversity appears bleak. A cover story in Nature last May revealed that "the world's oceans have lost over 90% of large predatory fish, with potentially severe consequences for the ecosystem." Nearly every major fishery around the world has declined or collapsed.

[coral reefs]
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This July, Sciencexpress reported a loss of 80% of coral reefs across the Caribbean over the past three decades, and this is part of a disturbing global trend. In Southeast Asia, 88% of coral reefs are threatened. In that same region live over half the world's species of cone shells, the amazing natural chemists I discussed earlier.

Worldwide, it is estimated that some 30% of the world's reefs have been lost since the 1980s. This is the ecosystem with the greatest biodiversity on earth, yet less than 10% of it has been catalogued.

[dust storm]
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Microbial pathogens are suspects in some of the coral reef declines in the Caribbean. African dust storms, such as the one illustrated in this satellite image, take 5-7 days to cross the Atlantic and carry hundreds of millions of tons of dust, which may convey some coral disease pathogens and other pollutants.

Indeed, iron in dust from the Sahara Desert may be helping to stimulate conditions favorable for harmful algal blooms in the Gulf of Mexico. It is thought that dust clouds carrying microorganisms, nutrients and other contaminants may be part of the complex deterioration of coral reefs around the globe.

Balanced against these sobering statistics are the new technologies that offer tremendous capabilities to sustain marine biodiversity even now.

Looking back at what I wrote in Science in 1983, we have come a long way beyond what I call the "grab, smash, streak and test approach" we traditionally have used to screen for promising compounds.

Through genomics and proteomics we can harvest newly found compounds in a targeted, non-depleting, 21st century way. We no longer need to destroy diversity in order to exploit it—instead of harvesting huge amounts of organisms, we can work with their DNA.

We can also envision leap-frogging over the laborious and costly clinical trials that can bog down drug discovery—screening for toxicity and making a natural compound safer even before trials begin. As the late John Faulkner of Scripps Institution of Oceanography has put it, we can begin to use marine organisms as inspiration rather than as the source of the compounds we seek. Instead of scouring the seabed, we can insert a useful gene in another species and have it manufacture the desired product, without the harmful traits. As an example, there is renewed discussion about exploiting the potential of viruses as a shuttle to target delivery of a gene to a cell.

[pics of bioprospecting partnerships]
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As marine biotechnologists we can do much more to weave conservation into our professional activities. Healthy coral reefs can have huge economic benefits for coastal communities, offering both income and conservation incentive, yet few nations have the know-how and resources to develop plans for sustainable harvest.

On the one hand we can work to develop long-term collaborations with local scientists—both marine biotechnologists as well as those documenting local biodiversity. We can also communicate our results to the public, as concerned citizens.

Along these lines, a speech delivered by the president of the Biotechnology Industry Organization caught my attention. Carl Feldbaum's talk laid out a "foreign policy" for biotechnology. "As researchers prospect...," he said, "we must follow ethical guidelines that respect cultures and ensure fair compensation to indigenous peoples" including incorporating the principles of informed consent and benefit sharing. He also called on the biotechnology industry to "promote biodiversity on the path to achieving sustainable development."

[ICBG conceptual framework]
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A number of organizations including NSF, the National Institutes of Health, and other US agencies have sponsored a program that is creating models for ethical bioprospecting partnerships. These "International Cooperative Biodiversity Groups" have three goals: to discover natural products for pharmaceutical and agricultural development, to promote scientific and economic development, and to conserve biodiversity.

[ICBG principles]
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The ICBG has developed principles to govern bioprospecting. These include informed consent; designating partners' rights; protecting inventions; sharing benefits; equitable information flow; and respect for all relevant national and international laws.

As Josh Rosenthal of the Fogarty International Center explains, a range of benefits should be shared with a partnership's host country, including enhancing local capacity to make sound decisions about local resources, while fostering longstanding collaborations that produce better local scientific partners.

[global map showing current groups]
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We see here a map showing where current partnership groups are located, as denoted by the red stars. Of note here are the program's new goals to encourage projects involving microorganisms and marine resources. Among its accomplishments, the program numbers the discovery of more than 250 bioactive compounds, expanded laboratory and field research capacity in 12 countries, and new models for intellectual property rights and benefit-sharing.

[ending graphic - with quote]
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Twenty years from now, the confluences of new tools, disciplines and insights on sustaining marine life will take us to yet another watershed, which will reveal ever more clearly the rich connections between marine and human life.

Poets have always known them. Shakespeare himself drew these ancestral connections in his verse, "A Sea Dirge," which intones, "Full fathom five thy father lies/ Of his bones are coral made/ Those are pearls that were his eyes..." The man evoked in the poem "suffers a sea-change/Into something rich and strange."

In our time, we have really just begun to explore the "full fathom five" and beyond in search of models, pharmaceuticals, and clues to life itself for biotechnological treasures "rich and strange." Now we are borne on the accelerating confluences of science and engineering-which will foster a true sea-change in our field, if we can sustain our inheritance of biodiversity.



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