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These are the user uploaded subtitles that are being translated: 1 00:00:02,550 --> 00:00:04,640 This video was sponsored by NordVPN. 2 00:00:04,640 --> 00:00:12,120 Get 70% off and a chance of up to 3 years for free by using the link in the description. 3 00:00:12,120 --> 00:00:18,119 The Puffer fish, also called Blow Fish or Fugu: In terms of the potency of its toxin 4 00:00:18,119 --> 00:00:22,589 it is the most poisonous vertebrate in the ocean and the second most poisonous vertebrate 5 00:00:22,589 --> 00:00:26,119 in the world after the poison dart frog. 6 00:00:26,119 --> 00:00:31,609 It is estimated that only a mere 1-2 mg of pure puffer fish toxin could kill a grown 7 00:00:31,609 --> 00:00:32,609 man. 8 00:00:32,609 --> 00:00:38,390 To showcase just how little this is, a single drop of water equals about 50 mg. 9 00:00:38,390 --> 00:00:43,239 This minute amount is enough to kill you or around 10,000 mice. 10 00:00:43,239 --> 00:00:45,789 So let’s talk a little bit about this toxin. 11 00:00:45,789 --> 00:00:49,899 It is called Tetrodotoxin or TTX. 12 00:00:49,899 --> 00:00:54,109 It is named after the first group of animals it was discovered in - the Tetraodontidae 13 00:00:54,109 --> 00:00:56,200 or the Puffer fish. 14 00:00:56,200 --> 00:01:00,510 Of all the neurotoxins it is probably one of the most famous ones, frequently being 15 00:01:00,510 --> 00:01:02,870 featured in Movies and TV shows. 16 00:01:02,870 --> 00:01:08,330 It is also one of the most powerful neurotoxins know and is about 10-100 more potent than 17 00:01:08,330 --> 00:01:14,800 black widow venom and 1000-10000 times more toxic than cyanide when injected. 18 00:01:14,800 --> 00:01:17,880 Eating it is a lot safer but it is still deadly nonetheless. 19 00:01:17,880 --> 00:01:22,030 If you had the choice between swallowing TTX or the same amount of Plutonium you would 20 00:01:22,030 --> 00:01:25,280 have a better chance of survival going with plutonium. 21 00:01:25,280 --> 00:01:28,000 But how does it actually kill you? 22 00:01:28,000 --> 00:01:32,950 Tetrodotoxin is one of a few neurotoxins that binds to the so called voltage-gated sodium 23 00:01:32,950 --> 00:01:33,950 channels. 24 00:01:33,950 --> 00:01:38,460 In nerve cells these channels play an essential role in the process that allows the electrical 25 00:01:38,460 --> 00:01:43,890 nerve impulses our body uses to send information to be transmitted from one neuron to the other. 26 00:01:43,890 --> 00:01:49,230 By binding to and disabling these sodium channels TTX prevents the conduction of these nerve 27 00:01:49,230 --> 00:01:54,290 impulses which ultimately shuts down the communication between nerve cells and therefore the brain 28 00:01:54,290 --> 00:01:55,410 and the body. 29 00:01:55,410 --> 00:02:00,360 Puffer fish themselves are immune to the poison due to a mutation in the protein sequence 30 00:02:00,360 --> 00:02:01,680 of the sodium channel. 31 00:02:01,680 --> 00:02:04,730 But for most other organisms it is lethal. 32 00:02:04,730 --> 00:02:09,670 When consumed, a low dose of Tetrodotoxin typically produces tingling sensations and 33 00:02:09,670 --> 00:02:14,290 numbness around the mouth, fingers, and toes as well as a feeling of euphoria. 34 00:02:14,290 --> 00:02:18,950 These Symptoms usually start to occur between 15 minutes to 4 hours after eating. 35 00:02:18,950 --> 00:02:23,710 Higher doses produce nausea, vomiting, and diarrhea, breathing difficulties and irregular 36 00:02:23,710 --> 00:02:28,420 heart beat as well as loss of motor skills and extensive paralysis. 37 00:02:28,420 --> 00:02:32,470 The paralysis will worsen to the point where the sufferer will become unable to even move 38 00:02:32,470 --> 00:02:35,720 a finger all while being fully conscious. 39 00:02:35,720 --> 00:02:41,290 Death usually occurs after 4-6 hours but in extreme cases after as little as 20m either 40 00:02:41,290 --> 00:02:44,700 due to paralysis of the heart or the respiratory system. 41 00:02:44,700 --> 00:02:48,060 There is no approved medication or antidote for it. 42 00:02:48,060 --> 00:02:52,780 In Puffer fish the toxin is concentrated mainly in the ovaries, liver, intestines, and to 43 00:02:52,780 --> 00:02:55,260 less extent in the skin. 44 00:02:55,260 --> 00:02:59,900 Originally it was thought that they synthesize the toxin themselves, however we now know 45 00:02:59,900 --> 00:03:05,350 that the toxin is instead produced by bacteria that they likely obtain from their prey and 46 00:03:05,350 --> 00:03:08,670 that form a symbiotic relationship with the animals. 47 00:03:08,670 --> 00:03:13,510 This is supported by the fact that puffer fish born in aquaculture and fed on a TTX-free 48 00:03:13,510 --> 00:03:19,890 diet have no toxin in their body can however become toxic once released into the wild. 49 00:03:19,890 --> 00:03:24,709 These bacteria can also be found in a variety of other marine and terrestrial species that 50 00:03:24,709 --> 00:03:31,400 utilize Tetrodotoxin such as the blue ringed octopus, parrotfish, sunfish, moon snails, 51 00:03:31,400 --> 00:03:36,790 several species of crabs and starfish as well as some toads and newts, and these tiny marine 52 00:03:36,790 --> 00:03:42,880 flatworms that are one proposed food source of TTX in Puffer fish. 53 00:03:42,880 --> 00:03:47,630 The levels of toxicity depend on the species, the habitat and the time of year and seem 54 00:03:47,630 --> 00:03:52,010 to be at least in some form correlated to the reproductive cycle as they are typically 55 00:03:52,010 --> 00:03:56,630 significantly increased during spawning season – This might be to supply the eggs with 56 00:03:56,630 --> 00:04:02,099 the necessary TTX doses to keep them save from predators but the toxin might also function 57 00:04:02,099 --> 00:04:05,490 as a sort of sexual pheromone for puffer fish. 58 00:04:05,490 --> 00:04:09,880 Experiments have shown that they are able to smell TTX in the water, so the increased 59 00:04:09,880 --> 00:04:16,100 levels could mean that Puffer Fish are specifically attracted to the most toxic partners. 60 00:04:16,100 --> 00:04:19,709 Large individuals have enough toxins in their bodies to kill around 30 humans. 61 00:04:19,709 --> 00:04:23,419 That is enough to kill a fully grown great white shark. 62 00:04:23,419 --> 00:04:28,259 With these levels of toxicity there aren’t really any large predators that can realistically 63 00:04:28,259 --> 00:04:32,009 use them as prey at least not the most poisonous species. 64 00:04:32,009 --> 00:04:36,669 Even an adult Killer whale with its 2-4 tons of weight would probably feel very sick for 65 00:04:36,669 --> 00:04:39,289 a day or two after eating such a puffer fish. 66 00:04:39,289 --> 00:04:43,289 You would need to be a large baleen whale to be heavy enough to not be severely impacted 67 00:04:43,289 --> 00:04:55,960 by its toxin and even they might enter a trance-like state for a while. 68 00:04:55,960 --> 00:04:59,460 Dolphins have been filmed seeking out puffer fish for exactly this reason. 69 00:04:59,460 --> 00:05:03,479 They don’t eat them but catch them in their mouth and use them for a sort of chew toy 70 00:05:03,479 --> 00:05:04,699 for a while. 71 00:05:04,699 --> 00:05:08,479 The small amount of toxin released through the skin is not enough to kill the dolphins 72 00:05:08,479 --> 00:05:11,319 but it seems to make them incredibly high. 73 00:05:11,319 --> 00:05:15,879 Is plausible that for a blue whale more than 300 times larger swallowing a puffer fish 74 00:05:15,879 --> 00:05:20,400 whole could have a very similar effect, but such a scenario is of course unlikely at best 75 00:05:20,400 --> 00:05:24,309 given that baleen whales don’t typically feed in the tropical coastal waters puffer 76 00:05:24,309 --> 00:05:26,879 fish are most commonly found in. 77 00:05:26,879 --> 00:05:31,559 This sensation of euphoria and the tingling of the lips and tongue is also why puffer 78 00:05:31,559 --> 00:05:37,059 fish is considered a delicacy in many Asian countries particularly Japan - That and the 79 00:05:37,059 --> 00:05:40,449 thrill of eating something that could theoretically kill everyone in the restaurant. 80 00:05:40,449 --> 00:05:46,039 It is a bit like the food equivalent of Russian roulette, at least that’s how it feels. 81 00:05:46,039 --> 00:05:50,979 Because of this, Tetrodotoxin poisoning is and was historically by far the most common 82 00:05:50,979 --> 00:05:52,909 lethal marine poisoning. 83 00:05:52,909 --> 00:05:58,599 Archaeological evidence suggests that the people of Japan have eaten Fugu possibly for 84 00:05:58,599 --> 00:06:00,779 more than 2000 years. 85 00:06:00,779 --> 00:06:05,509 Because of the inherent danger its consumption was banned many times throughout Japans history 86 00:06:05,509 --> 00:06:10,969 and even today Fugu is the only food the Emperor of Japan is forbidden to eat. 87 00:06:10,969 --> 00:06:17,620 Between 1886 and 1963 there were 6400 cases of Fugu poisoning reported in Japan of which 88 00:06:17,620 --> 00:06:18,620 3800 ended in death. 89 00:06:18,620 --> 00:06:26,030 That’s an average of over 80 cases per year and a mortality rate of 60%. 90 00:06:26,030 --> 00:06:30,229 Most of the deaths however came from eating the liver which was and still is considered 91 00:06:30,229 --> 00:06:34,449 the tastiest part of the fish even though it holds most of its toxin. 92 00:06:34,449 --> 00:06:39,249 Since the serving of liver was outlawed in 1984 the number of cases but especially the 93 00:06:39,249 --> 00:06:44,289 mortality rate has dropped significantly - down to 3% in recent years. 94 00:06:44,289 --> 00:06:49,240 In Tokyo only a single person has died as a result of Fugu poisoning in a restaurant 95 00:06:49,240 --> 00:06:50,870 in the last 30 years. 96 00:06:50,870 --> 00:06:56,819 So despite its reputation is actually pretty safe to eat when prepared by a licences chef. 97 00:06:56,819 --> 00:07:01,279 Almost all of the roughly 40 yearly cases of and puffer fish poisoning in Japan occur 98 00:07:01,279 --> 00:07:07,210 when inexperienced people try to prepare the fish themselves which is needless to say extremely 99 00:07:07,210 --> 00:07:09,080 dangerous. 100 00:07:09,080 --> 00:07:14,029 But despite its deadliness this little fish might actually safe lives in the future. 101 00:07:14,029 --> 00:07:19,119 Tetrodotoxin has been found to be about 3000 times more potent than morphine which makes 102 00:07:19,119 --> 00:07:24,130 it a very attractive candidate for pain medication if we can find a way to release the toxin 103 00:07:24,130 --> 00:07:26,190 in a controlled and targeted way. 104 00:07:26,190 --> 00:07:30,409 Furthermore, because it doesn’t cross the brain blood barrier like morphine does is 105 00:07:30,409 --> 00:07:35,009 doesn’t have the negative side effects of opioids most notably their addictiveness, 106 00:07:35,009 --> 00:07:38,479 which has become a mature problem in the US and other countries. 107 00:07:38,479 --> 00:07:43,789 And because the effects of TTX cause no lasting tissue damage and are completely reversible 108 00:07:43,789 --> 00:07:48,659 with time it could become a long lasting very effective alternative to morphine that could 109 00:07:48,659 --> 00:07:53,409 be safely administered for week’s maybe months and therefore could be used to relieve 110 00:07:53,409 --> 00:07:59,469 chronic and neuropathic pain such as chemotherapy-induced pain which is one of the most common reasons 111 00:07:59,469 --> 00:08:02,939 that cancer patients stop their treatment early. 112 00:08:02,939 --> 00:08:07,729 With each Puffer Fish containing enough toxin to treat dozens of people this tiny but deadly 113 00:08:07,729 --> 00:08:12,830 fish could therefore become one of our most important allies in our continuous fight against 114 00:08:12,830 --> 00:09:49,160 cancer.11973

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