Pufferfish-A dangerous delicacy

by Matthew Norton

The sea is a dangerous place to live with many of its creatures under threat from bigger animals that want to eat them. Therefore, it makes sense to have defences in place, such as a hard shell to protect their soft flesh, a flexible body to squeeze into tight hiding places, or strong, muscular fins to quickly swim away from danger. Other sea animals produce and store toxic chemicals in their organs, which will poison any predator foolish enough to eat them.

For many species of pufferfish, the weapon of choice is tetrodotoxin which is a nasty neurotoxin that disrupting the electrical signals that pass through an animal’s nervous system. Under normal circumstances these signals are transmitted by the movement of electrically charged sodium ions in and out of the nerve cells, which moves the signal along (like a Mexican wave in a crowd).

Tetrodotoxin blocks the channels through which the sodium ions re-enter the nerve cells which, depending on the dose, weakens, or completely blocks the transmission of these electrical signals. Without properly functioning nerves the brain of the poisoned animal will struggle to tell it muscles to move, resulting in symptoms such as muscle weakness, paralysis and breathing problems.

Pufferfish article image 1
Pufferfish accumulate tetrodotoxin in their skin, liver, intestines and ovaries (depending on the species) which makes them deadly for most animals to eat.

Tetrodotoxin is clearly an effective deterrent against predators, but there are ways to develop a resistance to tetrodotoxin, such as changing the structure of the sodium ion channels, otherwise pufferfish would also suffer from its effects. Even predators with limited tolerance to tetrodotoxin, or no tolerance at all, may still be able to eat pufferfish without getting poisoned for two very good reasons.

Firstly, the toxicity differs between pufferfish species, which suggests that some species need less protection, or rely more heavily on other means of protection, such as puffing their bodies up, or sudden bursts of swimming activity.

Secondly, in most species, pufferfish are not born with tetrodotoxin defences, in fact they cannot produce the toxin themselves and instead keep cultures of toxin-producing bacteria in their bodies. They get these bacteria from their prey, who in turn get them from further down the food chain, but until they can accumulate a meaningful amount of tetrodotoxin from these bacteria they will be vulnerable to predators. The only exceptions are species who can accumulate the toxin in their ovaries, such as the Grass Puffer, Takifugu niphobles, and pass it on to their larvae.

This diagram roughly shows the process that tetrodotoxin interferes with. Sodium (Na+) ions are drawn into the nerve through open ion channels (left side) and flips the electrical charge inside the nerve from positive (+) to negative (-). Some of these sodium ions are drawn further down the nerve to where it is still negatively charged (positive and negative charges always attract), which opens up the next set of sodium ion channels and the cycle is repeated.

Pufferfish have adopted a strong anti-predator defence with their use of tetrodotoxin, but this strategy still has its limitations, which is probably why they have other defences in place. Some marine animals, such as cone snails and arrow worms, have even repurposed the toxin for catching and paralysing their prey, rather than defence. Nonetheless, the use of toxic chemicals for defensive purposes is still an inventive solution in the struggle to survive and not get eaten.

From a human perspective

There are a number of different animal groups that are poisonous to eat because they contain tetrodotoxin, but tetrodotoxin from pufferfish is worth paying attention to because we eat them. Human consumption of pufferfish is possible because the muscle of most species has very low concentrations of tetrodotoxin, which can be removed prior to consumption, and farmed pufferfish can be deprived of their supply of toxin-producing bacteria.

Unfortunately, there are still cases of tetrodotoxin poisoning, especially in Japan and the United States, due to pufferfish meat not being prepared properly, or a being labelled as a completely different, non-toxic, fish. This potentially fatal mistake (for the consumer) was even depicted in an episode of The Simpsons in which Homer Simpson thought he had eaten toxic pufferfish meat and only had 24 hours left to live.

Pufferfish is a seafood delicacy, especially in Japan and the United States, but because of the danger posed by tetrodotoxin in its flesh it has to prepared in restaurants by specially trained chefs.

Fortunately, we can also use tetrodotoxin as a painkiller by reducing the dose to a safe level (relatively speaking) that only weakens the electrical signals in affected nerves, specifically the nerves that tell the brain to feel pain from a specific body part. In modern medicine there it can be used to relieve pain in patients recovering from surgery and suffering from medical conditions that include arthritis, cancer and injuries to the spine and knee joints. Some evidence also suggests that pufferfish meat and eggs, which contained tetrodotoxin, was used in historical medical practices to treat arthritis, leprosy and muscle convulsions.

Tetrodotoxin may be a poison, but carefully controlled doses can, and have, been used to relieve pain from certain medical conditions such as arthritis (top right) and leprosy (bottom right).

Non-fatal doses of tetrodotoxin from pufferfish may also be used insidious purposes such as voodoo zombification. Stories of this practice, where the recently deceased are believed to be magically raised from dead by a voodoo priest, or priestess, originated in Haitian folklore among slaves brought from Africa in the 18th century. These stories received more widespread attention in the western world in the early 20th century and was soon depicted in western literature and early zombie films such as “White Zombie”.

Tetrodotoxin’s role in voodoo zombification was suggested in the 1980’s by Wade Davis, an anthropologist (the study of humans) from Canada who suggested that the practice is partly based in reality. Instead of magic, he suggested that a special ‘zombie powder’ applied the by voodoo priest/priestess contained tetrodotoxin, extracted from pufferfish, caused a death-like state in the victim, who seemingly rises from the dead as the toxin wears off.

In Haitian folklore voodoo zombies remain under the control of the priest or priestess as personal slaves, which directly inspired the 1932 film called “White Zombie” (right).

Davis’s claims were controversial at the time, and remain so to this day for a variety reasons. These include specific criticisms over how Davis conducted his research while he was in Haiti, such as confusion around the samples of zombie powder he collected and the fact he didn’t test its effects on mice. There were also personal attacks against Davis, such as claims he was involved in morally questionable activities in Haiti and that, by writing two popular books, he was exploiting the publicity around his findings. These arguments aside (I’d rather not get involved regardless of their validity) the scepticism over Davis’s claims is well founded, but if they are true it would hardly be the first radical theory to be rejected at first and then widely accepted at a later date. When Charles Darwin argued that species evolve by natural selection and Galieo Galilei argued that the Earth orbits around the Sun they were seen as radical by many people at the time.

It is bizarre to think that this one toxin can poison us, relieve us from pain and make us think we’ve risen from dead. Admittedly, the role of tetrodotoxin in voodoo zombification is questionable at best, much like the existence of the practice itself. However, even the idea that this mythical practice could exist in the real world has a powerful effect on human culture and zombies as an icon in popular culture.

Pufferfish article image thanks for reading
Thanks for reading

Sources

Wikipedia. 2018a. Tetraodontidae. https://en.wikipedia.org/wiki/Tetraodontidae. Last accessed 11/02/2019

Wikipedia. 2018b. Tetrodotoxin. https://en.wikipedia.org/wiki/Tetrodotoxin. Last accessed 11/02/2019

Kiernan et al. 2005. Acute tetrodotoxin‐induced neurotoxicity after ingestion of puffer fish

French et al. 2010. The tetrodotoxin receptor of voltage-gated sodium channels—perspectives from interactions with μ-conotoxins

Narahashi. 2008. Tetrodotoxin

Narahashi et al. 1964. Tetrodotoxin blockage of sodium conductance increase in lobster giant axons

Chau et al. 2011. On the origins and biosynthesis of tetrodotoxin

Noguchi et al. 2006. TTX accumulation in pufferfish

Lee et al. 2000. A tetrodotoxin-producing Vibrio strain, LM-1, from the puffer fish Fugu vermicularis radiatus

Yang et al. 2007. Analysis of the composition of the bacterial community in puffer fish Takifugu obscurus

Matsumura. 1998. Production of tetrodotoxin in puffer fish embryos

Itoi et al. 2014. Larval pufferfish protected by maternal tetrodotoxin

Venkatesh et al. 2005. Genetic basis of tetrodotoxin resistance in pufferfishes

Cohen et al. 2009. Public health response to puffer fish (tetrodotoxin) poisoning from mislabeled product

Harkup. 2018. Tetrodotoxin: the poison behind the Japanese pufferfish scare. https://www.theguardian.com/science/blog/2018/jan/17/tetrodotoxin-the-poison-behind-the-japanese-pufferfish-fugu-scare. Last accessed 11/02/2019

Sutaria. 2019. Current Uses. https://sites.tufts.edu/tetrodotoxin/uses/. Last accessed 11/02/2019

Wikipedia. 2018c. White Zombie (film). https://en.wikipedia.org/wiki/White_Zombie_(film). Last accessed 11/02/2019

Wilson. 2019. Haitian Zombie Powder. https://science.howstuffworks.com/science-vs-myth/strange-creatures/zombie1.htm. Last accessed 11/02/2019

Nieto et al. 2012. Tetrodotoxin (TTX) as a therapeutic agent for pain

Inglis. 2010. The zombie from myth to reality: Wade Davis, academic scandal and the limits of the real

Kao and Yasumoto. 1990. Tetrodotoxin in” zombie powder”.

Guercio. 2017. From the Archives: The Secrets of Haiti’s Living Dead. https://www.harvardmagazine.com/2017/10/are-zombies-real. Last accessed 11/02/2019

Image sources

Helixitta. 2015. [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)%5D. https://commons.wikimedia.org/wiki/File:Propagation_of_action_potential_along_myelinated_nerve_fiber_en.svg

Yamaguchi Yoshiaki from Japan. 2008. [CC BY-SA 2.0 (https://creativecommons.org/licenses/by-sa/2.0)%5D. https://commons.wikimedia.org/wiki/File:Pufferfish_%E3%81%B5%E3%81%8F(%E3%81%B5%E3%81%90)_(2236877860).jpg

James Heilman. 2010. [CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)%5D. https://commons.wikimedia.org/wiki/File:Rheumatoid_Arthritis.JPG

Jean-noël Lafargue. 2005. [FAL (http://artlibre.org/licence/lal/en/)%5D. https://commons.wikimedia.org/wiki/File:Zombie_haiti_ill_artlibre_jnl.png

All other images are public domain and do not require attribution

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