CURRENTS
Fall 2001

Bioprospecting in Bermuda:
Exploring the Marine Rainforest
Dr. Hank Trapido-Rosenthal explains why secrets to curing disease may be right on Bermuda's doorstep

Many people have heard about the possibility of discovering new pharmaceuticals in the earth's rainforests, but the promise of lifesaving drugs and other chemicals hidden in our oceans remains a virtual secret. BBSR's location on an island surrounded by coral reefs and deep ocean makes it an ideal base from which to explore the "marine rainforest."

BBSR has formed a partnership with Diversa, a leading-edge biotechnology firm based in San Diego, to develop a bioprospecting program that takes advantage of the many species found in the inshore and offshore marine ecosystems that lie right on Bermuda's doorstep.

This new bioprospecting program applies the tools of genomics and genetic engineering to the task of searching for bioactive molecules that have potential uses in the medical and industrial worlds. My colleges and I are investigating the vast, untapped microbial biodiversity found both in the open ocean and in association with the organisms found in Bermuda's shallower inshore waters.

Our focus is on microbes because of the incredible genomic diversity that, collectively, these organisms possess. During the three billion years life has been evolving on earth, these microbes have developed the molecular machinery necessary to thrive in every ecological condition present on the planet. These include: temperatures that range from below freezing to above boiling; salt concentrations that range from almost zero to saturation (10 times the salinity of seawater); pressures that range from those found 20,000 feet below sea level to those found 20,000 feet above; and energy sources that range from sunlight to sulfur to petroleum. The overwhelming majority of these organisms, more than 99 percent, have never been cultured and thus remain taxonomically obscure to science. Yet from the remaining fraction of one percent that humans have domesticated have come a vast array of compounds of immense medical and economic value.

A classic example of a microbial product that has been tremendously useful to human health is penicillin. The microbial enzymes and enzyme pathways that are used in the production of wine and cheese are examples of microbial molecules that have a long history of contributing to human economic activities (if not necessarily human health!).

In coral reefs, like those surrounding Bermuda, biodiversity resides not so much in the corals themselves (more than 800 species of reef-building corals world wide), but with the huge number of species, many microbial, that live in harmony with them (estimates range from one million to nine million).

Sea sponges are ideal candidates for bioprospecting because each can live in symbiosis with dozens of different species of bacteria. DNA from the sponges and the associated bacteria can be collected simultaneously.

Many of the microbes BBSR scientists are interested in live in symbiotic association with the plants and animals found in Bermuda's inshore waters. For instance, as much as 50 percent of the dry weight of a sea sponge may consist of bacteria, and a single sponge can be populated by dozens of different bacterial species. Marine scientists believe that these microbial symbionts are often responsible for the extraordinarily wide range of interesting chemicals for which sponges are famous.

In the past, marine natural products chemists did their bioprospecting by homogenizing large quantities of a particular organism, for example a sponge, in organic solvents such as methanol or hexane. They would then look for chemicals of interest in these homogenates. When they discovered something of interest, often in vanishingly small amounts, they would have to collect and process more of the sponge to obtain more of the valuable chemical. To obtain marketable quantities of this compound, huge quantities of sponge would need to be harvested. Such harvesting would be damaging to a large coral reef ecosystem, such as Australia's Great Barrier Reef; it would be devastating to a small reef environment such as Bermuda's.

One alternative to large-scale harvesting of wild populations would be "farming" of the sponge. Another would be to use the tools and techniques of organic chemistry to synthetically produce chemicals of interest. Both of these techniques have their own environmental and economic expenses and pitfalls.

Dr. Hank Trapido-Rosenthal (left) and Dr. Manuel Costa, of the University of the Azores, amplify DNA from marine organisms in DNA Thermocyclers. This is part of the cloning process.

With the advent of genomic and genetic engineering technologies, an environmentally friendly and economically viable alternative to the old-fashioned bioprospecting techniques has been developed. Now scientists at BBSR can collect a small sample of sponge, extract the DNA from that sponge and its associated microbes, and clone it into a domesticated strain of laboratory bacteria. The cloned DNA contains all of the blueprints necessary for the biological synthesis of whatever chemicals the sponge and its symbionts were capable of producing. At this point, it becomes possible to literally "train" the genetically engineered bacteria to create large quantities of the sought-after drug or other chemical of interest.

Scientists have high hopes that this low-impact bioprospecting method will enable BBSR and Diversa to discover numerous valuable chemical treasures beneath Bermuda's waters.

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