On love dart and poison dart

The peculiar behaviors of some animals may be understood in terms of their powers that seem to influence evolution. Whereas a group of land snails use sexual power, a group of sea snails use predatory power. Incidentally during their — 50 million years of evolution, the predatory sea snails have developed several aspects of the present-day pharmaceutical industry — disposable needles (harpoons, in the case of cone snails), and tactics for drug discovery.

To harpoon with love

A living proof of how sexual power can achieve evolutionary success is the so-called “love dart” that some bisexual land snails shoot at their prospective mates. Love darts are produced by sexually mature snails, and are used as part of the episodes prior to mating. Each of the two snails tries to shoot darts into the other before mating. Similar to a needle, the love dart has the ability to pierce. In their work on Cantareus aspersus (brown garden snail, also known as Cornu aspersum, formerly Helix aspersa), Chase and Blanchard (Proceedings of the Royal Society B: Biological Sciences, vol. 273, pp. 1471-1475, 2006) conclude that the snail can optimize reproduction by accurately shooting the darts. They confirm that successful dart shooting serves to enhance paternity, and that this occurs because the dart transmits mucus containing a substance that can cause contractions of the organs receiving the spermatophore. The contractions enhance the survival of many sperm cells and the probability of successful fertilization.

The love dart is a harpoon-like material often made of calcium carbonate. Hunt (Tissue and Cell, vol. 11, pp. 51-61, 1979) has described the love dart of Helix pomatia (Roman snail) as a four-bladed, hollow spike-like structure, wherein calcium carbonate is mainly in the form of very tiny crystals that are not more than 0.5 micrometer (one micrometer is equal to 10^-6 meter) in size and are assembled into blocks of much bigger size. Also, protein is present as component of the calcium carbonate phase, as lining to the tubular core, and as external covering. The love dart is produced and stored in a muscular structure called the dart sac.

To harpoon with poison

A case showing that predatory power can influence evolution is the so-called “poison dart” used by a large group of venomous sea snails, the cone snails of genus Conus. Because the cone snail is slow-moving, it uses radula with a harpoon in order to capture prey such as fish, worm or mollusk, depending on the prey type of the snail. The harpoon is typically hollow and barbed and is mainly made of chitin, a large polymer of N-acetylglucosamine (substance derived from the sugar glucose). It is attached to the radula that is stored in the radula sac, a pocket found in the posterior wall of the mouth cavity. When the snail senses a prey, it stretches its flexible proboscis toward the prey. The harpoon, still attached to the radula and loaded with toxins from the venom duct, is shot into the prey. With this action, the snail quickly paralyzes fish prey with neurotoxins. The cone snail withdraws the radula, pulling into the mouth the captured fish which the snail then swallows. After devouring the fish, the cone snail regurgitates the indigestible matter such as bones, scales, and disposable harpoon.

The venom of cone snail may contain more than a hundred different toxins, and venom composition extensively varies among Conus species. The venom contains sleep-inducing and pain-relieving toxins, which the cone snail can use to calm down the prey before immobilizing it with paralytic toxins that can be lethal. Several toxins can be fatal to humans; in fact, cases of human fatalities were noted for Conus geographus (geography cone).

Pharmacology lesson from cone snails

The cone snails, comprising — 700 living species, are among the most successful sea animals. Each Conus species uses the poison dart to capture prey, to defend itself against predators or possibly to deter competitors. For these goals, the cone snails have produced a plentiful assortment of neurotoxins that are mainly peptides (“small proteins”) called conotoxins or conopeptides. The biochemical features of the peptides are very distinct among Conus species. An individual conopeptide is selectively aimed at a specific cell-surface receptor or ion channel in the nerve cell. As a consequence, the conopeptides have shown various pharmacological functions and uses.

Looking into the evolutionary trends of cone snails provides a lead to pharmacological success. Thus, research on cone snails and their peptides sums up a collaborative discovery approach toward the development of new medications for nervous system disorders, such as neuropathic pain, epilepsy, Parkinson’s disease, Alzheimer’s disease, among others. The venom of cone snails is an alternative natural source of substances that may have therapeutic value comparable to or may be even better than those obtained from traditional sources. Thus, the evolutionary tactics by which the cone snails have produced numerous peptides with great specificity and high affinity for their molecular targets have imparted lessons for the development of new therapeutic drugs.

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Dr. Elsie C. Jimenez is a retired professor of chemistry of the University of the Philippines Baguio. She is a member of the Philippine-American Academy of Science and Engineering. For almost 15 years, she has undertaken research on peptides from cone snails, for which she holds several US patents. Currently she is also involved in research on toxins and proteins associated with Philippine harmful algal blooms. E-mail her at [email protected].