Scientists and physicians are always on the lookout for new substances that can kill harmful cells, such as tumor cells. One rich source of these "cytotoxic" (toxic to cells) natural products is the coral reef. The sea and the organisms that live in it, like the rainforest, are a vast untapped resource of such products.

On coral reefs, complicated food webs develop that include seaweeds and other plants, mollusks and other grazers, and fish. The balance in a web is maintained in part by cytotoxic products that influence which organisms eat which. Reef organisms sport a rich and varied assortment of chemical deterrents that harm predators or at least keep them away. They also use a number of physical defenses, such as tough body structures, in order literally to "save their skins."

Valerie Paul, Ph.D. has been documenting for more than a decade some of the fascinating chemical and physical defense factors found in reef organisms. Her studies on reefs off Guam and elsewhere in Micronesia show, on the one hand, that variety is indeed the spice of reef defensive life, and, on the other hand, that quite different organisms sometimes use similar strategies to protect themselves.

Many reef organisms carry highly toxic chemicals, but others carry their defenses in a nontoxic, inactive form. The Halimeda seaweeds, which are among the most commonly seen algae on tropical reefs, are in this second category. Moments after predatory fish begin eating the Halimeda plants, stored defensive chemicals are activated at the sites where the plants were injured. Although injury-induced activation of defensive chemicals has been documented in a number of terrestrial plants, Paul was the first to describe this phenomenon in a marine plant.

Scientists think that the activation strategy spares plant cells from the chemical injuries that might be inflicted during the storage of highly toxic compounds. But, for any given plant, this means that a certain amount of tissue must be lost before fish are deterred. However, in the long run -- that is, for the seaweed population as a whole -- such a defense is cost-effective: after a few distasteful encounters, many predatory fish are able to recognize the noxious plants on sight and avoid them.

A different approach to protection involves the recycling of toxins. Paul has studied a group of small, slow-moving, grazing seahares (these are mollusks with arched backs) whose nutritional mainstay is a specific seaweed that contains a toxic substance. The seahares eat the seaweed and suffer no adverse effects from the toxins they ingest. The defensive chemicals are then concentrated and stored in the seahares' digestive glands. Later, when predatory fish attempt to eat the seahares, the recycled seaweed toxins provide protection.

Paul has observed this "pass the toxin" strategy in other pairs of reef organisms as well, including mollusks that eat seaweeds and nudibranchs (mollusks without shells) that eat sponges. In the latter pair, the toxins of the sponges may actually serve first to attract the nudibranchs and later to protect them from potential predators. The recycling strategy is not unique to reef organisms; it has also been found in certain insects that feed on terrestrial plants.

In addition to active, inactive, and recycled toxins, reef organisms also use an "innocent bystander" strategy for self-protection. Paul has observed certain crabs grazing on a seaweed that produces a strong fish deterrent. The crabs do not store or reuse the deterrent. They merely benefit from a physical association with the deterrent-rich seaweed. As long as a crab is camouflaged in the seaweed, the fish that normally would eat the crab leave it alone.

Paul estimates that there are probably tens of thousands of interesting natural products in the sea; already, some thousands of products have been harvested and identified. Some of the specialized, and often quite potent toxic substances could have biomedical uses -- they might kill cancer cells, halt inflammatory responses, or deter microbes and viruses -- and others may be effective insecticides for use in agriculture. Although Paul does not evaluate cytotoxicity in her own laboratory, she collaborates with several researchers in Hawaii who are examining the cell-killing properties of the natural products she has isolated.

Paul is a professor at the Marine Laboratory of the University of Guam in Manilao. She is also director of the Minority Biomedical Research Support Program there, which is supported by the National Institute of General Medical Sciences at NIH.