Spotlight Toxicant: Tetrodotoxin

By Alexis Wormington

Ah, the humble pufferfish. Known for its particularly unique defensive strategy, the pufferfish is likely one the world's most comical marine fish, next to the blobfish (yes, it’s a thing, Google it for a giggle). However, this funny little fish packs a deadly punch – it secretes tetrodotoxin, one of the most potent neurotoxins on the planet!  
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Tetrodotoxin, although known colloquially as the pufferfish toxin, is actually produced by a variety of marine and even terrestrial animals – not just the pufferfish! It has been found in certain species of octopus, starfish, frogs, and even newts. Although there is some scientific debate regarding the how tetrodotoxin is produced in these species, there is a large amount of new evidence that suggests that these animals accumulate the toxin from gastrointestinal bacteria - the literal definition of a toxic relationship!  

Figure 1: Some animals that produce the neurotoxin tetrodotoxin. Astropecten scoparius (left), the rough-skinned newt (middle), and the blue-ringed octopus (right).

Figure 2: The chemical structure of tetrodotoxin.

Tetrodotoxin works by blocking ion channels, which disrupts the function of neurons and causes paralysis. The toxin is extremely potent, meaning that the fatal dose is very small compared to other toxic substances. The oral lethal dose of tetrodotoxin in mice is around 0.000334 grams/kilogram, which is at least 25 times more toxic than cyanide, although some sources claim that it is anywhere from 100 to 2500 times more toxic! Despite decades of research into this topic, there is currently no existing antidote for tetrodotoxin poisoning. ​

Luckily for most of us, it's pretty difficult to be exposed to tetrodotoxin. The animals that produce it tend to mind their own business, so it's an unlikely thing to come across during a casual day at the beach. Most exposures actually occur through the consumption of fugu (pufferfish meat) that has been improperly prepared. However, despite the popularity of fugu in countries like Japan, fugu poisoning is rare and only affects a few people annually. Japanese chefs must be licensed to prepare the dish, and only a handful of restaurants have it on their menu. Additionally, some Japanese companies are raising pufferfish that do not produce the toxin with the hope that more people can consume fugu safely. 

Figure 3: Fugu, a common delicacy in Japan.

Although tetrodotoxin is obviously dangerous in its undiluted form, its neurological effects make it useful for medicinal and research purposes. At very dilute concentrations, it is potentially therapeutic - showing promise for use in ​​pain relief and thought to reduce drug cravings in heroin addicts. Tetrodotoxin is also used extensively in the research of ion channels and organ function., a valuable tool for the field of neuroscience. Just like botulinum toxin (aka Botox), tetrodotoxin has a place in human society as well, and there is still much to learn from it.