How Poisons Work: Tetrodotoxin

by Joseph DeSisto

This is the first of a series of short articles, each featuring a different type of poison or venom used by animals.

Poisons and venoms are some of the most complex substances in nature, often containing hundreds of different chemicals, each with a particular purpose. As technology advances, scientists have begun to look at some of these chemicals, usually proteins, and try to figure out what they do.

The deadly southern blue-ringed octopus (Hapalochlaena maculosa). Photo by Bernard Dupont, licensed under CC BY-SA 2.0.

The deadly southern blue-ringed octopus (Hapalochlaena maculosa). Photo by Bernard Dupont, licensed under CC BY-SA 2.0.

In some cases, the results give us a new perspective on an animal’s biology: rattlesnake venom, for example, contains a unique protein that allows the snake to track its prey after the initial strike. In other cases, we discover potentially useful surprises: giant centipede venom contains a single protein that inhibits pain in mice, using the same chemistry as morphine, but with greater efficiency. However, regardless of whether the results are useful to us, studying nature’s chemical weapons gives us a whole new appreciation and understanding of the creatures that wield them.

Tetrodotoxin is the poison of choice for a variety of animals, especially in the ocean. These include blue-ringed octopuses, cone snails, moon snails, certain angelfish, some ribbon worms, a handful of amphibians, and the puffer/triggerfish order Tetraodontiformes, for whom the toxin is named. Many of the animals that use tetrodotoxin are brightly colored, a warning to passers-by. Would-be predators, save the immune and the unlucky, heed this warning well.

An inflated pufferfish (Diodon holocanthus). Photo from Williams et al. (2010), licensed under CC BY 2.5.

An inflated pufferfish (Diodon holocanthus). Photo from Williams et al. (2010), licensed under CC BY 2.5.

Tetrodotoxin, sometimes abbreviated TTX, is a complex molecule that prevents its victims’ nerves from functioning properly. This eventually leads to paralysis, and death comes when the muscles that control breathing no longer receive signals from the nervous system. Basically, you suffocate. Humans can get TTX poisoning when they eat improperly-prepared pufferfish, but stings from blue-ringed octopuses and cone snails (both from the southwestern Pacific) are also a possibility if you are foolish enough to pick them up.

Although many animals use TTX, none of them actually manufacture the toxin themselves. Instead bacteria generate the toxin, to their host’s benefit. In exchange, the bacteria are allowed to live safely within their host’s body — the bacterium Pseudoalteromonas tetraodonis, for example, makes its home within the livers and skins of pufferfish.

A toxic moon snail (Naticarius orientalis) from East Timor. Photo by Nick Hobgood, licensed under CC BY-SA 3.0.

A toxic moon snail (Naticarius orientalis) from East Timor. Photo by Nick Hobgood, licensed under CC BY-SA 3.0.

The rough-skinned newt, from British Colombia and the western United States, has the bacteria needed to make TTX for itself — as a result, this newt has few natural predators. Two animals, however, have managed to work around and even benefit from the rough-skinned newt’s toxins, all without toxin-producing bacteria of their own.

The only animal capable of eating an adult rough-skinned newt is the garter snake. After ingesting the newt, any other predator would almost certainly die, but a few populations of garter snakes have evolved an immunity to TTX. What’s more, the snakes are able to sequester the toxins within their own bodies, so that the garter snakes themselves become poisonous (Williams et al. 2004).

The extremely toxic rough-skinned newt (Taricha granulosa). Photo by Rennett Stowe, licensed under CC BY 2.0.

The extremely toxic rough-skinned newt (Taricha granulosa). Photo by Rennett Stowe, licensed under CC BY 2.0.

Although many snakes inject toxins with their fangs, and so are venomous, garter snakes that eat rough-skinned newts are the only snakes that can truly be considered poisonous. The difference is that venomous animals have to inject their poisons into predators or prey, via fangs or stingers, while poisonous animals are laced with their chemical weapons and are dangerous to eat.

The other TTX-robber is, unexpectedly, a caddisfly. Caddisflies are insects whose larvae resemble caterpillars, but live underwater and surround themselves with cases made from pebbles, twigs, and other debris. Most are scavengers, eating decomposing plant matter and tiny invertebrates, while the flying adults are short-lived and do not feed.

A Limnephilus caddisfly larva, in its protective case made of twigs. Photo by Tom Murray, used with permission.

A Limnephilus caddisfly larva, in its protective case made of twigs. Photo by Tom Murray, used with permission.

A few predatory species in the genus Limnephilus, however, have developed an unusual appetite for rough-skinned newt eggs, which also develop in the water. These eggs are loaded with TTX, and the toxin-resistant Limnephilus larvae manage to eat so many that even the caddisfly adults are toxic (Gall et al. 2012).

Even though many marine invertebrates contain tetrodotoxin, we still don’t know how many contain the bacteria that make it, versus how many, like the caddisfly, “steal” the toxin from their TTX-laced prey. Certain sea slugs, for example, are often washed on shore where they are eaten by beach-combing scavengers such as dogs. In New Zealand, several dogs have died after eating sea slugs that contained TTX (McNabb et al. 2009), and in Argentina, a population of the same slugs appears to have become invasive (Farias et al. 2015). Yet we still do not know whether they have their own TTX-generating bacteria.

A toxic sea slug, Pleurobranchaea meckelii. Photo from Wägele and Klussmann-Kolb (2005), licensed under CC BY 2.0.

A toxic sea slug, Pleurobranchaea meckelii. Photo from Wägele and Klussmann-Kolb (2005), licensed under CC BY 2.0.

Experiments have shown that certain populations of sea slugs have TTX, while others do not (Khor et al. 2014) — just like the garter snakes of North America. Does this mean the sea slugs are obtaining TTX from some unknown, toxic prey item? The same researchers conducted a survey of all the marine invertebrates that these slugs might be eating, testing everything for TTX. The only positive result was a toxic species of sand dollar, but the sand dollars didn’t produce nearly enough TTX to explain the huge amounts found in sea slugs.

Ignorance has consequences, and there is still plenty of exploring left to do. The slugs may in fact make tetrodotoxin themselves (using bacteria). A more enticing possibility, and just as likely, is that there are still more toxic animals on the sea floor, waiting to be discovered.

One of the very first articles I wrote for this site featured the same sea slugs mentioned in this one, but that was when my only readers were a few sympathetic family members. If you’re curious about sea slugs, and/or you want to know the difference between a nudibranch and a pleurobranch, you can read that article here.

I also recently wrote about how rattlesnake’s use their venom to track once-bitten prey (mentioned in the second paragraph of this article). To learn more about that, click here. It’s amazing, I promise.

Cited:

Farias, N.E., S. Obenat, and A.B. Goya. 2015. Outbreaks of a neurotoxic side-gilled sea slug (Pleurobranchaea sp.) in Argentinian coasts. New Zealand Journal of Zoology, published online: DOI: 10.1080/ 03014223.2014.990045.

Gall, B.G., A.N. Stokes, S.S. French, E.D. Brodie III, and E.D. Brodie Jr. 2012. Predatory caddisfly larvae sequester tetrodotoxin from their prey, eggs of the rough-skinned newt (Taricha granulosa). Journal of Chemical Ecology 38(11): 1351-1357.

Khor, S., S.A. Wood, L. Salvitti, D.I. Taylor, J. Adamson, P. McNabb, and S.C. Cary. 2014. Investigating diet as the source of tetrodotoxin in Pleurobranchaea maculata. Marine Drugs 12(1): 1-16.

McNabb, P., L. Mackenzie, A. Selwood, L. Rhodes, D. Taylor, and C. Cornelison. 2009. Review of tetrodotoxins in the sea slug Pleurobranchaea maculata and coincidence of dog deaths along Auckland Beaches. Prepared by Cawthron Institute for the Auckland Regional Council Technical Report 2009/108.

Williams, B.L., E.D. Brodie Jr., and E.D. Brodie III. 2004. A resistant predator and its toxic prey: persistence of newt toxin leads to poisonous (not venomous) snakes. Journal of Chemical Ecology 30(10): 1901-1919.

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3 responses to “How Poisons Work: Tetrodotoxin

  1. Pingback: Venom-Laced Spider Webs | Beautiful Nightmares

  2. Pingback: Poison-Laced Silk | Beautiful Nightmares

  3. Pingback: Poisonous Frogs, Beetles, and Birds | Beautiful Nightmares

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