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Original subtitles

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The Puffer fish, also called Blow Fish or Fugu: In terms of the potency of its toxin

it is the most poisonous vertebrate in the ocean and the second most poisonous vertebrate

in the world after the poison dart frog.

It is estimated that only a mere 1-2 mg of pure puffer fish toxin could kill a grown

man.

To showcase just how little this is, a single drop of water equals about 50 mg.

This minute amount is enough to kill you or around 10,000 mice.

So let’s talk a little bit about this toxin.

It is called Tetrodotoxin or TTX.

It is named after the first group of animals it was discovered in - the Tetraodontidae

or the Puffer fish.

Of all the neurotoxins it is probably one of the most famous ones, frequently being

featured in Movies and TV shows.

It is also one of the most powerful neurotoxins know and is about 10-100 more potent than

black widow venom and 1000-10000 times more toxic than cyanide when injected.

Eating it is a lot safer but it is still deadly nonetheless.

If you had the choice between swallowing TTX or the same amount of Plutonium you would

have a better chance of survival going with plutonium.

But how does it actually kill you?

Tetrodotoxin is one of a few neurotoxins that binds to the so called voltage-gated sodium

channels.

In nerve cells these channels play an essential role in the process that allows the electrical

nerve impulses our body uses to send information to be transmitted from one neuron to the other.

By binding to and disabling these sodium channels TTX prevents the conduction of these nerve

impulses which ultimately shuts down the communication between nerve cells and therefore the brain

and the body.

Puffer fish themselves are immune to the poison due to a mutation in the protein sequence

of the sodium channel.

But for most other organisms it is lethal.

When consumed, a low dose of Tetrodotoxin typically produces tingling sensations and

numbness around the mouth, fingers, and toes as well as a feeling of euphoria.

These Symptoms usually start to occur between 15 minutes to 4 hours after eating.

Higher doses produce nausea, vomiting, and diarrhea, breathing difficulties and irregular

heart beat as well as loss of motor skills and extensive paralysis.

The paralysis will worsen to the point where the sufferer will become unable to even move

a finger all while being fully conscious.

Death usually occurs after 4-6 hours but in extreme cases after as little as 20m either

due to paralysis of the heart or the respiratory system.

There is no approved medication or antidote for it.

In Puffer fish the toxin is concentrated mainly in the ovaries, liver, intestines, and to

less extent in the skin.

Originally it was thought that they synthesize the toxin themselves, however we now know

that the toxin is instead produced by bacteria that they likely obtain from their prey and

that form a symbiotic relationship with the animals.

This is supported by the fact that puffer fish born in aquaculture and fed on a TTX-free

diet have no toxin in their body can however become toxic once released into the wild.

These bacteria can also be found in a variety of other marine and terrestrial species that

utilize Tetrodotoxin such as the blue ringed octopus, parrotfish, sunfish, moon snails,

several species of crabs and starfish as well as some toads and newts, and these tiny marine

flatworms that are one proposed food source of TTX in Puffer fish.

The levels of toxicity depend on the species, the habitat and the time of year and seem

to be at least in some form correlated to the reproductive cycle as they are typically

significantly increased during spawning season – This might be to supply the eggs with

the necessary TTX doses to keep them save from predators but the toxin might also function

as a sort of sexual pheromone for puffer fish.

Experiments have shown that they are able to smell TTX in the water, so the increased

levels could mean that Puffer Fish are specifically attracted to the most toxic partners.

Large individuals have enough toxins in their bodies to kill around 30 humans.

That is enough to kill a fully grown great white shark.

With these levels of toxicity there aren’t really any large predators that can realistically

use them as prey at least not the most poisonous species.

Even an adult Killer whale with its 2-4 tons of weight would probably feel very sick for

a day or two after eating such a puffer fish.

You would need to be a large baleen whale to be heavy enough to not be severely impacted

by its toxin and even they might enter a trance-like state for a while.

Dolphins have been filmed seeking out puffer fish for exactly this reason.

They don’t eat them but catch them in their mouth and use them for a sort of chew toy

for a while.

The small amount of toxin released through the skin is not enough to kill the dolphins

but it seems to make them incredibly high.

Is plausible that for a blue whale more than 300 times larger swallowing a puffer fish

whole could have a very similar effect, but such a scenario is of course unlikely at best

given that baleen whales don’t typically feed in the tropical coastal waters puffer

fish are most commonly found in.

This sensation of euphoria and the tingling of the lips and tongue is also why puffer

fish is considered a delicacy in many Asian countries particularly Japan - That and the

thrill of eating something that could theoretically kill everyone in the restaurant.

It is a bit like the food equivalent of Russian roulette, at least that’s how it feels.

Because of this, Tetrodotoxin poisoning is and was historically by far the most common

lethal marine poisoning.

Archaeological evidence suggests that the people of Japan have eaten Fugu possibly for

more than 2000 years.

Because of the inherent danger its consumption was banned many times throughout Japans history

and even today Fugu is the only food the Emperor of Japan is forbidden to eat.

Between 1886 and 1963 there were 6400 cases of Fugu poisoning reported in Japan of which

3800 ended in death.

That’s an average of over 80 cases per year and a mortality rate of 60%.

Most of the deaths however came from eating the liver which was and still is considered

the tastiest part of the fish even though it holds most of its toxin.

Since the serving of liver was outlawed in 1984 the number of cases but especially the

mortality rate has dropped significantly - down to 3% in recent years.

In Tokyo only a single person has died as a result of Fugu poisoning in a restaurant

in the last 30 years.

So despite its reputation is actually pretty safe to eat when prepared by a licences chef.

Almost all of the roughly 40 yearly cases of and puffer fish poisoning in Japan occur

when inexperienced people try to prepare the fish themselves which is needless to say extremely

dangerous.

But despite its deadliness this little fish might actually safe lives in the future.

Tetrodotoxin has been found to be about 3000 times more potent than morphine which makes

it a very attractive candidate for pain medication if we can find a way to release the toxin

in a controlled and targeted way.

Furthermore, because it doesn’t cross the brain blood barrier like morphine does is

doesn’t have the negative side effects of opioids most notably their addictiveness,

which has become a mature problem in the US and other countries.

And because the effects of TTX cause no lasting tissue damage and are completely reversible

with time it could become a long lasting very effective alternative to morphine that could

be safely administered for week’s maybe months and therefore could be used to relieve

chronic and neuropathic pain such as chemotherapy-induced pain which is one of the most common reasons

that cancer patients stop their treatment early.

With each Puffer Fish containing enough toxin to treat dozens of people this tiny but deadly

fish could therefore become one of our most important allies in our continuous fight against

cancer.

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