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Horizons
INNOVATION 

By Malorye A. Branca

October 10, 2003 | From coastal tide pools to thermal vents in deep trenches, the ocean's expansive surface masks a vast array of different habitats, each one home to creatures genetically adapted to that particular environment. Scores of these organisms are vanishing from the seas — victims of human encroachment, exploitation, and pollution. Because they are hidden beneath the ocean, we may never learn of the creatures that eventually disappear.

Many sea organisms are microscopic, and some are restricted to micro-niches, such as "caves under a single island," says Wolfgang Sterrer, curator of the Bermuda Natural History Museum. For marine biologists, the threat to these habitats is particularly frustrating because so much of the ocean remains unexplored. The Southern Ocean around Antarctica, for example, is thought to contain about 4,500 species — comparable to the 6,000 or so species estimated to live in the Mediterranean or tropical regions.

Now, thanks to sequencers and online databanks, the genomic revolution is reaching into the ocean and helping to preserve its heritage, identify new medicines, and combat pollution. Saving species remains difficult, but preserving their DNA has grown easier, and many prominent scientists are in hot pursuit.


Little Creatures 
Massachusetts-based Ocean Genome Legacy (OGL) is seeking to accelerate the process. In 2001, New England Biolabs founder Donald Comb established this not-for-profit organization with the purpose of preserving marine organisms' DNA. OGL's board of trustees includes Nobel laureates Sydney Brenner and Richard Roberts. The organization currently has only three staff members, but it also has a clear mission and a practical plan.

 Yippie-ki-DNA! OGL trustee Wolfgang Sterrer rides a rare species of tropical ocean fauna, the whale shark (Rhincodon typus). 
Part of OGL's mandate is to overcome technical hurdles. For example, it's working to develop better tissue culture techniques for marine invertebrate cells. "One of the biggest bottlenecks is that many of these organisms can't be cultivated at all," explains Wolfgang Hess, OGL's director. That's particularly problematic with rare creatures, which can't be collected in bulk. Another vexing question is defining what constitutes the "creature" itself. Recently, Sterrer points out, "an organism was reclassified from mollusk to worm." It had originally been misclassified because of mollusk remains in its digestive tract.

So far, the group has banked fewer than 100 samples, but Hess is expecting help: "The idea is to build this as a collaboration with the entire marine biology community. Others will take the samples from all over the world and send them to us for storage." To accomplish that, OGL needs the cooperation of biologists trained in traditional classification methods and able to pick and pack the right specimens.

Hess' first goal is to establish OGL's genome libraries as important resources in order to obtain further buy-in from marine biologists.

Initially, OGL will concentrate on collecting ocean sponges and cyanobacteria — single-celled, photosynthetic bacteria, also called "blue-green algae." Sponges may represent the first multicellular animals, thought to have evolved about 800 million years ago. Cyanobacteria comprise the backbone of the ocean's food chain and are responsible for generating most of the oxygen that comes from the ocean and for most of the carbon-fixing that occurs there.

Another aim is to learn how these organisms have adapted to their environments. As part of a project begun before he joined OGL, Hess and colleagues recently discovered considerable genetic diversity among several strains of the cyanobacteria Prochlorococcus (Rocap, G. et al. Nature 424, 1042-1047; 2003; and Dufresne, A. et al. PNAS 100, 10020-10025; 2003).

They examined three strains, two adapted to low light and one found where light is abundant. Surprisingly, even the low-light forms had very different genomes — one had 50 percent more genes than the other. "We expected these would be highly related organisms," Hess says, "but despite their small genomes, they differed by hundreds of genes." The compactness of these genomes offers an interesting glimpse into evolution. "A core gene set defines what is needed for photosynthesis," Hess says.

While OGL is focused on preservation and basic research, practical results could eventually emerge. Sponges, "bags of cells" as Sterrer affectionately calls them, have emerged as a major source of powerful, putative anti-cancer compounds. Supposedly, sponges evolved these chemicals as a means of self-defense. The National Cancer Institute's (NCI) Natural Products Branch reports that 30 such marine-derived compounds are currently in preclinical or clinical oncology trials; at least a dozen of these compounds were found in sponges.

Recently, the Australian Institute of Marine Science signed an agreement with NCI to provide U.S. researchers with access to specimens from the Great Barrier Reef and surrounding areas, and it has delivered the first 400 marine organism samples. NCI will screen extracts from organisms such as soft corals, sponges, and starfish for anti-tumor activity. Companies such as Nereus Pharmaceuticals are also getting into the game. Nereus describes itself as "a pioneer in drug discovery and development from marine microbial sources" and is pursuing preclinical candidates for a variety of indications, including cancer.


Keeping It Clean 
J. Craig Venter, meanwhile, is searching the ocean for something quite different. "We hope to discover new species and metabolic pathways that can help us clean up the environment," he says, adding, "I think our environment and what we are doing to it is one of the most critical issues facing humanity." In particular, he'd like to find a way to recapture some of the carbon being pumped into the atmosphere.

Predictably, Venter's plan is ambitious. His Institute for Biological Energy Alternatives (IBEA) plans to shotgun-sequence the ocean. Starting with the Sargasso Sea, his team is simultaneously sampling, sequencing, and reassembling all the microbial genomes they can find. Venter says his team has already tested the concept of doing such a mass sequence reassembly, and "it works." He anticipates a published report from the Sargasso work within a year. "Our first view of many of these new species will be from having their genetic code," he says. "This is the most exciting of all the major science projects I've done. It's high-throughput species and complete genome discovery." The U.S. Department of Energy recently awarded IBEA $9 million.

Whether anything remarkable comes from OGL or other groups, everyone involved agrees that cataloging the ocean's DNA is "worth doing, for its own sake," as Venter says.

"The ocean is not only the cradle of life — it supports an incredible diversity of life," Sterrer says. He points to living fossils, such as the lonely coelacanth and the far more common horseshoe crab. Even here, a practical use has emerged: The horseshoe crab has long been the source of a valuable enzyme used in bacterial toxin assays.









For reprints and/or copyright permission, please contact  Jay Mulhern, (781) 972-1359, jmulhern@healthtech.com.