What makes puffer fish poisonous?

In Japan it takes 3 or more years or rigorous training to become a Fugu chef and the pass rate for the exam is less than 40%. Fugu is a dish prepared from pufferfish, which is potentially lethal due to the presence of Tetrodotoxin (TTX). Budding chefs learn how to carefully remove the most toxic parts of the fish without contaminating the meat. Even though the liver of the fish is considered by some to be the tastiest part, its also the most poisonous organ. With such high stakes, restaurants serving Fugu are controlled by law, but there are around 20-40 incidents a year in Japan, with a fatality rate of around 7%.  Most of the fatalities aren’t associated with restaurants, but with home preparations. Never has the phrase “I’m dying to eat” been more apt.

The symptoms of ingesting a lethal dose of TTX include dizziness, exhaustion, headache, nausea and difficulty breathing. The victim remains conscious but cannot speak or move. Breathing stops and asphyxiation follows.  There is no known antidote. Treatment consists of emptying the stomach, giving the victim activated charcoal to absorb the TTX and putting them on life support until the poison has worn off. You can add in whatever prayers you feel like at that point. If the patient survives the first 24 hours then recovery over a few days is common.

So, what on earth is the pufferfish doing with this potent neurotoxin? It turns out that in the marine environment pufferfish aren’t alone. TTX is also found in blue ringed octopus, Astropecten star fish, Xanthid crabs and some newts and toads too. But despite its widespread appearance in the animal kingdom, none of these creatures are actually synthesising the TTX. The toxin is produced by bacteria that infect or live in the animal, and the animal concerned uses the TTX as a defensive biotoxin, and sometimes also as a venom eg octopus and arrow worms (Chaetognaths).
TTX acts by blocking sodium ion channels. Nerve cells have to pump sodium ions outside of the cell in order to be ready to transmit a signal. Sodium ions can’t cross cell membranes, so a special protein gateway exists in the nerve cell membrane that helps move the sodium out. Block this protein and the nerve cells will lose their ability to send a signal. This prevents the nerve from being able to send messages to muscles, resulting in reduced muscle movement. There are slightly different sodium ion channel proteins in the nerves controlling skeletal muscle and those controlling cardiac muscle. Victims of TTX poisoning will experience progressive paralysis throughout their body, whilst remaining conscious until shortly before death. A truly awful way to go.

TTX turns out to be remarkably toxic. The lethal dose of cyanide is 8.5mg per kg of bodyweight, but it would take only 4% of that amount of TTX to be lethal. TTX can be absorbed orally, by ingestion, by injection or through abraded skin. As the TTX levels are due to bacteria, there is a seasonal, geographical and species variation. It’s no wonder that the Fugu chefs need years of training. Poisonings from TTX are almost exclusively associated with the consumption of pufferfish from Indo-Pacific regions, but this is mainly because pufferfish just aren’t eaten as commonly elsewhere. In New Zealand in 2009 several dogs died after eating grey side gilled seaslugs (Pleurobranchus maculate) found washed up on beaches. The slugs were found to have ingested high levels of TTX.
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Naturally occurring TTX has been used in traditional Chinese medicine for over 4000 years to treat convulsive disease. In 1774 Captain James Cook recorded that his crew ate locally caught tropical fish and fed the left overs to the pigs kept on board. The crew had mild symptoms (numbness and shortness of breath) but by the morning all the pigs were dead. The crew had a very lucky escape, although its not known if they had pork for lunch the next day!