Pharmacology: Drugs from the Sea

Researchers will go anywhere and test anything in the hope of finding medicines to use against diseases and disorders that by present methods are either difficult to treat or incurable. One of their most fortuitous finds was made in a Peoria (Ill.) market, where they scraped from an overripe cantaloupe the parent strain of mold that fathered millions of doses of penicillin. Now that most of the world’s land surface has been finecombed for microbes that might yield new antibiotics, the scientists are turning to the sea. One useful drug, cephalothin (which is effective against many germs that are resistant to penicillin), has already been developed from a mold that was recovered near a sewer outlet in the sea off Sardinia. The search, recently intensified, extends from the Sea of Japan to the frigid waters of Antarctica, from the tepid shallows of coral reefs in the Caribbean to the far-western Pacific.

Last week 202 specialists in half a dozen sciences met at the University of Rhode Island for a roundup conference on the progress and problems connected with mining the seas for drugs. Almost to a man, they complained of lack of funds—a shortage intensified by recent cutbacks in governmental grants—and proclaimed their support of Senator Warren Magnuson’s bill to set up a National Institute of Marine Medicine and Pharmacology. In speech after speech they pointed out that the vast majority of all known forms of animal life are found in the sea, which they expect to yield a proportionately rich harvest of medically useful chemicals. Dr. Paul R. Burkholder, famed for his discovery of chloramphenicol* (in a Venezuelan soil mold) more than 20 years ago, prodded the pharmaceutical industry to speed up its testing of sea-spawned compounds that show antibiotic promise, a number of which he himself has isolated.

Esoteric Substances. In fact, six drug companies were represented at the Rhode Island conference. Some are already active in the field, testing such esoteric substances as paolin I, an antibacterial compound, and paolin II, an antiviral agent. Both were extracted from the juices of the abalone by Dr. Chen Pien Li at the National Institutes of Health. Similar extracts from quahaugs (thick-shelled clams) have been found to be active against some forms of cancer in mice. So far, chemicals from shellfish appear to have only moderate potency, but the sea offers an almost infinite variety of other potential sources, such as algae, corals and sponges, and the bacteria that live in or on them.

Marine pharmacologists have extracted alginic acid from algae and seaweeds, and have made salts (alginates) with a wide variety of medicinal properties. Some help tablets to disintegrate more rapidly in the stomach. Others form the basis of anti-clotting drugs and of preparations to control surface bleeding. Sodium alginate has the exciting ability to reduce man’s absorption of radioactive strontium by about 90%.

The most biologically potent chemicals so far extracted from marine life are the poisons that primitive creatures use for self-protection. That does not discourage the seagoing biologists. After all, they point out, the vegetable poison curare has proved invaluable as a muscle relaxant that is used with general anesthesia for surgery. The Japanese are already using molecular modifications of marine venoms as medicines.

Paul Burkholder, 66, who is now at the University of Puerto Rico and works in a laboratory at Mayagüez, also serves as senior marine scientist for Lederle Laboratories. Some of his antibacterial finds have come from sponges collected from as far away as Australia’s Great Barrier Reef and Palau in the Caroline Islands. When he arrived in Rhode Island last week, he had scarcely dried off from a scuba-diving, sponge-hunting expedition on the outermost edge of the Caribbean, between the British islands of Virgin Gorda and Anegada. Burkholder made his dives with an assistant, Robert Brody, who is completing his doctoral work on the gorgonians, or “soft corals.” Together they snipped off specimens of the most familiar gorgonian, the purplish fan coral, and a variety of sponges (of which about 5,000 species are known).

Semisynthesis. In the boat from which they worked, Dr. John Webb put the specimens into jars filled with alcohol. Ashore, within a few hours, some were quick-frozen, others were dried, and all were flown to Lederle’s labs at Pearl River, N.Y. There the tedious and time-consuming process of searching for medicinally useful compounds began with the preparation of crude extracts. It will continue through a variety of screening tests that will determine whether the extract is active against such familiar microbes as the staphylococcus and other causes of human disease.

If an extract proves to be active, the next stage of testing will be more difficult: isolating the individual ingredient responsible for the activity. Even more difficult is the task of determining the chemical identity of the isolated substance. Once that is done, it must be tested in animals to find out whether its germ-killing powers outweigh whatever undesirable side effects it may have. If the compound proves both safe and effective enough to be tested in man, the laboratory chemists will face the task of either synthesizing it or using the natural product as the base for a semisynthetic drug, the technique that is used in producing cephalothin.

In the search for drugs from the sea, from five to seven years may well elapse from the underwater snipping of a sponge specimen to the marketing of an antibiotic. But the seafaring scientists are confident that eventually the seas will yield a whole new pharmacopoeia of valuable drugs.

*The most effective drug against typhoid fever, psittacosis and Rocky Mountain spotted fever, but commonly misused for minor infections.