This article, continuing from my previous one about snails, was inspired by a guest lecture for the Life Science Institute at the University of Michigan by Dr. Baldomero Olivera of University of Utah. Header image is of Conus furvus, a snail-hunting cone snail from Olango Island, Cebu, collected by fishermen in shallow water.
In the warm lapping tides of tropical seas, brightly colored schools of fish dart through bundles of leaf-like kelp and crabs scurry sideways over rocks along the seafloor. One of the more dangerous creatures in this habitat found buried in the soft sand or dwelling among the reefs, are cone snails – a venomous predatory sea snail. Moving at literally a snail’s pace across the sea floor, “dangerous” and “predatory” might seem odd adjectives for these shelled gastropods, but a venomous sting from certain species of cone snails can be deadly.
Slow and steady
Due to their slow motility, which makes a high-speed chase impossible, many cone snails construct a harpoon-like structure called a radula for predation. More like a modified tooth, these harpoons are attached to the inside of the snail’s mouth, tucked away like a spy’s hidden gear. The radula is loaded with venom which paralyzes small fish instantly, making reeling in the catch much easier.
Upon further observation, however, the cone snail venom doesn’t just paralyze fish. Exposure to the released toxin causes a variety of biological impacts. Sometimes released into the surrounding water, schools of fish subject to gastropod toxins swim in circles, become sedated, and hypnotized towards and into the snail’s mouth. How does the venom cause so many different outcomes?
Nervous venoms
Venom itself is made of the same building blocks as proteins, amino acids. Because they are much shorter than proteins, they are called peptides, putting them in the same biological class as insulin and antibodies. The molecular targets of individual venom components are equally as diverse, but many of them primarily act on and alter the nervous system of prey.
Normally responding to ions like sodium or small molecules like adrenaline, membrane-bound protein channels in neurons can be triggered by venom peptides. Toxins will trap a channel in a particular state, where particular channels will normally open and close to propagate a signal across the brain. For example, forcing particular channels to stay open causes a never-ending signal propagation resulting in a seizure and muscle spasms for the prey, just like a nerve gas. These toxins, obviously detrimental to fish, have also caused at least 27 human deaths within a few minutes from being punctured by their proboscis.
Crude venom containing many different peptides, these toxins made by cone snails (and other plants and animals in general) are a primitive combinational drug therapy. Collecting snails and harvesting cone snail’s venom sacks, researchers have found that the venom coated on the snail’s harpoon can contain over 100 different components. With the 500 species of cone snails, this means there are over 50 thousand pharmacologically active compounds produced by these predatory gastropods! The combination of these toxins is how the fish subjected to the toxins have a wide variety of responses.
The snail’s prescription
Certain fish-hunting cone snails have particular combinations of toxins they administer their prey that are unique amongst different species. Because the covert nature of predatory snails, their attack strategies have been named after the secret political fractions that plot against governments, or “cabals.” One group of species uses its harpoon proboscis to puncture and administer a “lightning strike cabal” that combines a quick-acting muscle spasm followed by paralysis (Group A). Different species go after its prey with a “nirvana cabal” that immobilizes schools of fish with a toxin that induces a transcendental state, before engulfing the school and releasing a paralyzing agent (Group B). These different species of snails, though evolved independently from each other, both evolved to produce sets of toxins to capture prey.
Individual venom peptides from snails combinatorial cabals could be useful in therapeutic applications, due to their high selectivity for very specific types of receptors, especially pain management. In fact, several have already shown to have therapeutic potential, with several reaching human clinical trials. For example, a “toxin” that works on calcium channels is being administered for intractable pain. Another compound that increases ion channel opening is being developed for epilepsy. Instead of harvesting and sacrificing the tropical snails for their venom and purifying each component of interest out separately, the peptides themselves can be identified, synthesized in the lab, and further optimized to increase selectivity and decrease off-target effects.
Nature is endlessly surprising us, not only with “predatory snails” but also “medicinal toxins.” It reminds us that researching basic science, topics that aim to understand the foundations of science rather than studying an overtly applied system, can lead to useful benefits.
Working towards getting her Ph.D. in Chemical Biology at the University of Michigan, Sarah studies the molecular roads of the cell in the Cianfrocco and Verhey labs. Outside of research, she is active in science communication, editing for Michigan Science Writers, writing for her blog Annotated Science, and chairing the inaugural ComSciCon-Michigan 2018. Connect and chat about science, #scicomm, or open access with her on Twitter!