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Blockbuster Ocean Drugs on the Horizon?

Christine Dell'Amore
National Geographic News
May 14, 2009
 
As leads for new drugs on land dry up, medicine hunters are plunging into the ocean in search of the next blockbuster pharmaceutical.

Harvesting ocean organisms for medicinal purposes—called marine bioprospecting—has accelerated in recent years as scientists seek new antibiotics and cancer treatments.

"Bottom line, the marine microbial environment is very rich, because it's never been exploited before," said Kobi Sethna, president of the small biotech company Nereus Pharmaceuticals, which specializes in marine microbes.

Though the blue part of the planet was largely ignored during the drug rush of the past half century, it's a natural place to look, experts say.

Of the 36 known phyla—a taxonomic rank below kingdom—17 occur on land and 34 live in the ocean, making the seas "by far the highest biodiversity environment on the planet," said William Fenical, distinguished professor of oceanography and pharmaceutical science at University of California, San Diego.

"It would be difficult to overlook such a massive resource for chemical diversity and drug discovery," Fenical said.

Close to 25 drugs derived from marine life—such as bacteria, sponges, and tunicates—are currently in clinical trials.

Special Properties

In 1928, British bacteriologist Sir Andrew Fleming realized that a rare spore of fungus—Pencillium notatum—had floated from another lab through the air and landed in his culture plate of bacteria, killing some of it.

That early discovery of what would become the widespread antibiotic penicillin spurred an intensified effort to explore Earth's forests and wild places, which have proven to be repositories for some of today's major drug advances.

Fifty percent of drugs made for humans are derived in some way from nature, Fenical said.

But by the 1970s, scientists had realized that terrestrial microorganisms had been thoroughly explored, prompting a few early "pioneers" to turn their gaze seaward, Fenical said.

These pioneers were attracted by unique ocean organisms with special chemical properties not seen on land.

For instance, the severe ocean environments of little to no light and extremely cold temperatures have given rise to unusual—and mostly unstudied—survival strategies in ocean creatures, scientists say.

Such survival strategies coincidentally fight diseases in people as well.

For instance, some marine organisms produce population-control compounds that, when given to a person, work in a similar way: Instead of reducing the number of offspring, the compounds inhibit the growth of malignant tumors.

So "rather than inventing the wheel," people can benefit from millions of years of evolution, Nereus's Sethna said.

(Related: "Oil Platforms, Deep Seas Mined for New Drugs.")

Though opposition from conservationists has often dogged companies that scour rain forests for the next miracle drug, marine bioprospecting shouldn't impact the ocean environment, experts say.

Many of the drugs are easily synthesized into molecules in the lab, so that just a small amount of an organism, such as half a sponge, is all that needs to be collected.

In the Works

Though the first push into ocean medicine centered on antibiotics and cancer-cell killers, the field has grown more sophisticated, said Raymond Andersen, a chemistry professor at University of British Columbia. Andersen studies metabolites, or the byproducts of chemical processes produced by marine organisms.

For instance, some marine organisms, such as sponges and fungi, contain compounds that can inhibit an enzyme in the body secreted by a type of tumor called indoleamine-2,3-dioxygenase. The enzyme tricks the body into not attacking the tumor, Andersen said.

Another marine compound acts as a "corrector" for people who have cystic fibrosis, the most common genetic disease among Caucasians. The molecules grease the path for proteins in the body to reach the cell membrane, where the proteins restore mucus production required to prevent infections of the airway.

Andersen's lab has had two compounds enter phase-II clinical trials for treating soft-tumor cancers and asthma, respectively.

Clinical trials have three phases. During phase-II trials, an experimental study drug or treatment is administered to a group of about 100 to 300 people to see if it is effective and to further evaluate its safety.

Nereus's Sethna also has two drugs in the works.

One, currently in phase-II trials, was derived from a fungus that grows on sea grass in the Bahamas. The medicine destroys the established vascular system of a tumor—in combination with chemotherapy—for people with non-small-cell lung cancer, which has an average survival rate of seven months.

The second drug, taken from bacteria in ocean sediment, stops proteasomes—strong enzymes that break down proteins—from destroying proteins that would otherwise protect against cancer.

The drug—which is geared toward people with multiple myeloma, melanoma, and lung and pancreatic cancers—is finishing up phase-I trials, Sethna said.

During phase-I trials, researchers test an experimental drug or treatment in a small group of about 20 to 80 people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

No Laughing Matter

But marine bioprospecting still hasn't made the splash its backers were hoping for.

For one thing, Big Pharma hasn't gotten totally on board. If companies funded drug discoveries from marine microbes at anywhere near a third or half of the money spent on other drugs, there would be three times as many marine drugs already available, Fenical pointed out.

"It's discouraging that industry has taken such a standoff approach," he said.

Indeed, before Big Pharma shied away from the land, "people at board meetings would laugh when someone brought up the ocean," Sethna said.

But he said it's only a matter of time before marine drugs take off.

"If we succeed in two or three years and these products are purchased by pharma, the question is going to be asked, Where did you get them, and can [they] be duplicated?"
 

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