As I’ve said before, the definition of disease is fairly open and, in a sense, poisoning is a disease. Does it really matter whether a toxin is produced by something that’s in the body as opposed to outside the body? Perhaps. I don’t know. I don’t really care. Here’s this week’s article.
For a long time, the Japanese have known that people who ate puffer-fish liver would, on a somewhat regular basis, become paralysed, stop breathing and die. This became such a widespread problem that Japan banned the sale of puffer-fish liver in restaurants and markets in 1983. Despite this, people have not stopped eating it. In fact from 1997 to 2007, 470 people were admitted into hospital for puffer-fish poisoning, 30 of whom died. People eat these livers thinking they have special ways of neutralising the toxin. Experimentally (as seen as above) these ways do not work.
OK, Japan. Come here a minute, I just want to talk to you. Now I enjoy food. I’ll eat deliciously deep-fried food that will sever a good couple of months off my life. I’ll go on the occasional bender and increase my risk of cirrhosis. Hell, I’ve eaten at McDonald’s when it wasn’t even necessary. But really, Japan, there is no fish innard tasty enough to warrant risking dying a slow, frightening death by suffocation.
I want my fugu!
So scientists long knew that puffer-fish (fish of the Takifugu family) contained this toxin called tetrodotoxin (TTX). TTX stops nerves and muscles cells from conducting electricity by blocking sodium channels in the cell membrane. It’s like putting a plastic cap over an electrical terminal. Once you stop the flow of charge, you have no more electricity. This stops nerve action and you get paralysis.
Also, this plastic cap is shaped so that it only fits particular electrical terminals. Heart muscles have slightly different sodium channels that TTX can’t block. So, TTX-poisoned patients don’t die from a simple heart attack (which is what would happen if they were blocked); instead they are fully conscious as their diaphragm is slowly paralysed and they cannot draw more breath. But, if you don’t die, you eventually recover as your nerve cells produce more sodium channels so that current can flow and muscles can work again.
TTX is generally concentrated within the puffer-fish’s liver, ovaries/testes, skin and intestine. As long as you don’t eat these bits of the fish, you’ll be fine. The meat is OK to eat and apparently get a nice tingle on your tongue due to the low concentrations of TTX blocking the nerves on your tongue.
All this was well and good. Scientists thought that puffer-fish just make this toxin and this stopped animals from eating them, giving them an evolutionary advantage. It all fit in with their model. But when they looked closer, scientists found that not all puffer-fish species would produce TTX. Even weirder, fish of the same species in one area would make a lot of TTX, but in another area they would not.
[Side note: This may have led people to believe their traditional ways of neutralising toxins were working; they may not have been ingesting any TTX at all]
Curiouser and curiouser
In 1964, other scientists found TTX in the eggs of the California newt. Soon, they were finding TTX all over the place; in flatworms, in blue-ringed octopus, in starfish, in frogs, in crabs, in sea snails. It was a puzzle, only certain species in completely different families made TTX.
Maybe they all came up with a common defence against the common problem of being eaten. However, TTX as a molecule is pretty damn complicated. It’s hard to synthesise if you don’t have the prerequisite materials, and these animals didn’t seem to; at least, not any more than their TTX-free relatives.
So maybe it was from the environment. A simple experiment showed that this was the answer. A group took 6000 puffer-fish from farms. All farm-raised fish were TTX-free. They were kept in tanks, fed a normal diet and were still TTX-free. Then, they started feeding them bits of liver from wild puffer-fish, which contained low levels of TTX. Amazingly, these fish started concentrating TTX in their organs up to highly toxic levels. Other toxins were also fed to these fish, but they weren’t concentrated to the same level. Non-puffer-fish were also fed the same diet of liver, but not only excluded but also detoxified TTX. This conclusively showed that puffer-fish can selectively concentrate TTX from the environment.
But where was it coming from? A whole lot of studies looked at different bacteria dredged up from the sea and it turns out a lot of bacteria from different families all produced TTX. This is not all that surprising because bacteria (even of different species) have sex all the time and exchange bits of DNA. They were only produced in small amounts in these bacteria, but a phenomenon called bioamplification occurred.
Bioamplification in an ecosystem happens when there’s a substance that is efficiently absorbed by organism, but only slowly excreted. OK, so the TTX-making bacteria only make a little bit of TTX, but planktons eat a lot of these bacteria. So planktons have a higher concentration of TTX in them. In turn, various worms and shrimps eat a lot of plankton. TTX concentration is higher again in these animals. If you go up the food chain up to the puffer-fish, you’ve now got a metric butt-ton of the amount of TTX you started with. One more step to humans and you’ve got a toxic amount. This same mechanism of bioamplification has in the past caused toxic amounts of mercury to build up in sharks and other fish.
So there is the story of puffer-fish toxin. And, as with most of the Disease of the Week articles, the moral is: Don’t be an idiot. Stop eating poisonous things.