A Whole Pharma-Sea Out There? : Research: Two San Diego scientists plumb the depths for inspiration in developing drugs for human ills.

Take two bryzoans and call in the morning. Someday, a doctor might actually prescribe such a dose.

In quest of drugs, scientists have tapped much of the earth. Yet, one territory remains relatively untouched: the sea.

Dive into the world of sponges, tunicates, soft corals, gorgonians and bryzoans--an underwater panoply of creatures and organisms that might provide sources for medicine to treat diseases from arthritis to cancer, or even AIDS.

Two San Diego scientists, Bill Fenical and D. John Faulkner, believe the marine life and microorganisms dwelling fathoms deep could change our lives.

Fenical and Faulkner, recognized as pioneers in the field, respectively have isolated a chemical from a sea whip coral and another in a marine sponge that contain anti-inflammatory agents, which could be utilized to prevent swelling and pain from arthritis.

The hunt for new drugs has gained urgency as doctors find that some diseases, including tuberculosis, are developing resistance to drugs and others, such as AIDS and certain cancers, have evaded existing medications. The ocean, Fenical and Faulkner say, is man’s best alternative to the land for sources of future drugs.

“We can’t go to the soil forever because we are finding 95% of things in the soil are already known. We are going to have to go to the ocean,” said Fenical, a professor of chemistry at Scripps Institution of Oceanography. “It will be essential that we develop new agents. We need new drugs desperately.”

Marine-based medicines have not yet reached the marketplace, but they soon might.

“We are in all stages of success, from aspiring to have substances to having substances in clinical trials,” Fenical said.

Fenical has studied not only sea fans, sea squirts and other creatures, but in the last four years has searched for microorganisms, the microscopic bacteria that dwell in the ocean. More and more, he has become convinced that these tiny organisms--hundreds of which can be found in a single drop of water--may prove easiest to harvest and convert into medicines.

The process has its precedent--bacteria from bread mold led to penicillin. And Fenical hopes marine microorganisms will also strike pay dirt.

The research on marine life and microorganisms may sound like Jules Verne but it is the stuff of serious science, experts say.

“The potential is high for finding interesting new agents, not only for cancer and AIDS but other diseases because marine organisms tend to produce different types of chemicals compared to terrestrial sources,” said Gordon Cragg, chief of the natural products branch at the National Cancer Institute.

Researchers for years have utilized chemical agents found in nature. Aspirin comes from the bark of a willow tree. The anti-malarial drug quinine comes from fever-tree bark. Codeine and morphine are derived from opium poppies. Antibiotics such as penicillin and tetracyline are produced by microbial fermentation.

As scientists exhaust traditional routes, industry has become increasingly interested in the search for natural products that might yield new chemical agents. That search has broadened to include compounds that sound like ingredients for a witch’s spell, such as frog skin and the venom of the cone snail.

In scouring the earth, investigators found themselves in more and more remote places on land and, finally, at sea. Today, advances in technology have led to better diving gear and submersibles that make the ocean’s depths more accessible.

“It’s harder and harder to find new products in the terrestrial environment that are going to be clinically useful. . . . It becomes harder to find gold. You find little specks, but the marine environment is relatively untapped,” said Deborah Steinberg, a group leader in natural products research with the New York-based American Cyanamid, parent company of Lederle Laboratory.

“Almost everybody has looked to some extent at the marine environment because of the genetic diversity,” she said. “The potential is there we just have to find it.”

Only a relatively small number of scientists--50 or so around the world--work full time on the quest for medicines that could be gleaned from the oceans. In the U.S., marine organisms have supplied several chemicals that are likely to be developed into drugs:

* A Bahamian sponge yields the chemical discodermolide, a potent agent that may one day be used to suppress organ rejection after transplant surgery.

* A West Coast bryozoan--a moss animal that’s an aquatic invertebrate--supplies bryostatin, a potential anti-cancer product, which is being tested so researchers can determine if it can safely be administered to people.

* A Carribean tunicate, or a tubular, transparent, jellyfish-like creature that resembles a shell-less snail, provides an agent called didemnin B that is also being tested as an anti-cancer medicine.

* A Carribean gorgonian coral and a sponge found in the western Pacific are currently being studied as anti-inflammatory agents.

Faulkner and Fenical have spent much of their time studying creatures like the sponges, sea squirts and soft corals. These creatures lack the normal defense systems of spines and shells that deter hungry predators. Instead, they emit a chemical defense--it is the secret of these chemicals that they and others are now trying to unlock.

Faulkner discovered that one particular sponge in the South Pacific contains an agent called manolide. This compound prevents the release of enzymes that cause inflammation and pain, an agent that could be useful in arthritis medications and pain killers.

“Sponges do produce a great diversity of chemical types, more than any other marine invertebrate,” said Faulkner, a professor of marine chemistry at the University of California-SanDiego’s Scripps.

The procedure for obtaining chemicals from a sponge, Faulkner said, is simple. First, the sponge is placed in a freezer and then subjected to an ultra-sound bath, or “sonicated.” In everyday vernacular, that means you “shake the living daylights out of it,” he said.

After the chemical is purified, scientists measure to see how it reacts with cells in a test tube. Does it, for instance, inhibit cell growth? (A quality that would be useful in battling cancer.) In the case of the sponge found in the South Pacific, Robert Jacobs at the University of California in Santa Barbara determined how the chemical manolide acted to block enzymes.

For Faulkner, the world of sponges is particularly exciting because so much remains undiscovered. Scientists do not know how many different sponges exist.

“We are always encountering new species,” he said. “We expect we find half of all sponges in any one location.”

In a rare moment, Faulkner--who describes himself as a pessimist--leaned forward in his chair at his office and confessed: “I have no doubt there will be drugs that come from marine organisms.”

Yet, the process is long and arduous, and fraught with regulatory hurdles. As Fenical pointed out, taxol--a chemical derived from a yew tree that is considered to be a potentially effective anti-cancer agent--was discovered in the seventies but is just now being tried out.

“If we discover a substance today, you might see it in the year 2000,” Fenical said.

Some researchers believe that underwater farms could be established to grow any organisms that prove valuable. But Faulkner is skeptical. Nor does he believe that industry can--or should--rely on harvesting the ocean to glean sufficient quantities of a particular organism. Instead, he hopes that scientists will create a synthetic mimic of any chemical agents discovered as scientists now scan the seas.

“I personally think we shouldn’t be harvesting marine resources,” said Faulkner. “They should provide an inspiration for new drugs but not the materials themselves.”

The search for agents that could be utilized in drugs has taken the duo to obscure corners of the ocean here, in the Bahamas, Philipines, and off Australia’s west coast. The scientists can do preliminary testing aboard ship, checking to see if a substance demonstrates any potential effects when it’s placed in a tissue culture.

“Ninety-nine percent have no effect,” Fenical said.

The small number that show promise are further diminished as researchers discard chemicals that are too toxic. Even so, Fenical believes his sleuthing will pan out.

“In the cancer (drug) area, there are significant numbers of leads.” But Fenical cautioned, “We haven’t found anything yet that we’d say clearly will be developed.”

Fenical’s efforts to understand marine microorganisms could prove to be even more groundbreaking than his work with sea creatures.

“One drop of sea water has millions of cells and most are different; we don’t even know what they are yet, much less how to use them,” Fenical said. “By comparison of what’s known about soil bacteria, our studies are extremely primitive. This is the frontier.”

Fenical has found that some marine bacteria, accustomed to living in the depths of the ocean, require hydraulic pressure to stay alive on land. Other bacteria are able to survive extreme cold or heat--if they naturally grow near an underwater geothermal water source where temperatures can reach 350 degrees centigrade.

If they could be utilized, Fenical believes these microorganisms could change the way we live. He forsees a day when bacteria could be used to degrade pesticides. Or enable people to do laundry in cold water.

But such a future is years away at best.

“At least you can stand next to a (taxol-producing) tree for more than 45 minutes,” sighed Fenical. “Our ability to operate in the ocean is a lot worse. The ocean is one step more difficult to explore than terrestrial resources.”