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There are naturally occurring toxins on Earth that are SO poisonous that one drop could kill thousands of people. How is that possible? What about their chemical makeup makes them so poisonous? Join Hank Green for an exciting look into the dangerous world of natural toxins.

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It's a story straight out of a Bond film. On September 7th 1978 Bulgarian journalist Georgi Markov, a communist defector working for the BBC, was walking across the Waterloo Bridge in London when he felt a slight sting in his right thigh. He looked behind him and saw a man picking an umbrella up off the ground. By that evening he had developed a fever. Four days later, he was dead. The cause of death: poisoning. Markov had been assassinated using an umbrella rigged to fire a pellet laced with one of the most powerful natural toxins in the world: ricin.

Ricin is one of the deadliest natural substances that is not found in an animal. It's found in the beans of the castor plant. Just five hundred micrograms of the stuff, that's five ten thousandths of what a paperclip weighs, is enough to kill a man. And as potent as it is, ricin isn't even close to being the most poisonous natural substance on Earth. There are poisons that lurk in bacteria, plants, in fungi, ... all over the place, and they're not just found in exotic tropical locales or like 1970s London. They're pretty much everywhere and the fact is: they're there for good reasons.

But what is it about their chemical makeup that makes them so poisonous? How do their toxins attack the human body with such deadly efficiency? And why does my thigh suddenly feel all tingly... that an umbrella?!

[intro music]

 LD50 and the botulinum toxin

Not only is it morbid to list the most deadly toxins in Nature, it's also nearly impossible. There are a lot of plants and fungi and bacteria out there capable of killing you when eaten, inhaled, or injected. There are also a lot of variables that make it hard to quantify exactly how poisonous something is. Everything from the age of the victim to the antibodies in your system can affect how potent a substance is. There is, however, one exception: no one disputes that the most lethal toxic substance known to man, natural or otherwise, is produced by the tiny bacterium Clostridium botulinum. You probably know it by the disease it causes: botulism.

Just how deadly is the botulinum toxin? One way experts use to measure the lethality of a poison is a method called the 'lethal dose 50%', which is the dose required to kill half the members of a tested population. Since for obvious reasons you can't run these tests on humans, toxicologists usually get this number, often called the LD50, by using an endlessly unfortunate creature: the laboratory mouse.

LD50 is measured in a ratio of milligrams of toxin to kilograms of body weight, and in the case of the botulinum toxin it's about one nanogram. A billionth of a gram. Per kilogram. That means that a crystal of botulinum the size of a grain of sand would be enough to kill ninety six hundred people.

The bacteria are actually really common, and the spores they produce are found in soil and water all over the world. The problem starts when they germinate into active cells, at which point they begin to produce seven different toxins, four of which are deadly to humans. C. botulinum thrives in low-oxygen environments, and the ten to thirty cases reported each year in the US are usually the result of eating improperly canned food, since canning removes oxygen from food to preserve it. But if the food isn't heated properly the spores can stick around and set up shop in that can of Texas chili.

Botulinum spores can also be found in honey, and if you eat them they can find a nice oxygen-free nook of your body to hang out in. Kids and adults can ward off these spores before they germinate but infants can not. Which is why babies under twelve months old should never eat honey.

The spores are poisonous because they secrete a neurotoxin as a waste product. It works by blocking the release of a neurotransmitter called acetylcholine, which controls muscle contraction. This effectively makes every muscle in the victim's body go limp. Within several days without antitoxin the victim will asphyxiate from the inability to breathe. But yes! Thanks to science, and all of those poor lab mice, there is an antitoxin.

But why in the name of Mathieu Orfila would a bacterium evolve to fart the deadliest poison on Earth into its host? The answer remains a mystery. One theory is that the toxins are not aimed at the host, but rather at competitive bacteria. They create conditions where benign bacteria cannot survive, giving the evil bacteria a chance to spread. The host, in this case a human, is often just in the way of this process.


So compared to the botulinum toxins cyanide is like eating Play Dough. Well, not really. Do not eat cyanide. Not only will it kill your face, it's also one of the most rapidly acting poisons in the world. It's found in cigarette smoke, burning plastics, also a surprising number of natural foods including almonds and the seeds of apricots and apples. The LD50 of sodium cyanide, a common form, is 6.4 milligrams per kilogram of body weight, or over six million times less deadly than botulinum. But that said it's been a popular and effective tool of death for everyone from emperor Nero to Agatha Christie.

Cyanide is a carbon atom triple bonded to a nitrogen atom. What makes it such a fast killer is that it binds to proteins in your cells' mitochondria, the tiny power plants that keep your cells going, and keeps them from using oxygen, basically asphyxiating the body at a cellular level. It is true that some fruits and nuts contain cyanide. Apple seeds, for instance, contain a chemical that releases cyanide when it comes into contact with digestive enzymes. this is a good way to deter critters from digesting up all your seeds if you're a fruit, but there's not enough poison to kill them or us. Though I guess I wouldn't make a point of, like, eating a bowl of apple seeds.

The good news is that if you happen to suffer from cyanide poisoning there is always vitamin B12. The B12 that you get at the store actually contains cyanide as part of its gloriously complex molecular structure, so high doses of a precursor to the vitamin can literally pull the cyanide off of your poisoned mitochondria, and then you just pee out the poison in the form of B12.


Now, back to our Bulgarian friend. Well, the castor plant that killed him is next on our list. It's native to East Africa, but grows pretty much anywhere it's warm, including the South-Western United States. The toxin it produces, ricin, is a protein found in the castor bean, but the poison itself is made from the mash that's left over after grinding the beans into oil. When the oil is heated the ricin protein denatures or changes shape, which renders it harmless, so the toxin doesn't end up in the oil itself, which is used widely as a laxative. Or used to be. Not so much anymore. Cause gross.

But when inhaled, ingested, or injected, untreated ricin is readily absorbed by the body's cells. Once inside it inactivates the ribosomes, which manufacture proteins that your cells need to survive and reproduce, and once the protein train stops, life stops. Just a single ricin molecule is capable of inactivating fifteen hundred ribosomes per minute as it kills the cell. You may feel the effects within a few hours, but ricin is generally a slow acting poison, taking one to three days to cause death. Hence its popularity with assassins over the years who want to distance themselves from their crime.

The tiny platinum plug found in Markov's leg had two tiny channels drilled into it, each able to hold about one fifth of a milligram of the poison, but that was more than enough to kill Markov. Or any other human.

And the toxicity of ricin can change, depending on how it enters the body. Taken orally its LD50 is about twenty milligrams per kilogram of body weight, about eight castor beans worth of the poison. But if it's injected, like the way Markov got it, it's just one tiny microgram per kilogram. Antidotes to ricin, it's sad to say, are still in the early stages of development, but because ricin takes several days to kill, compounds are being investigated that can block it from reaching ribosomes in new cells in the body. And strangely enough ricin has also been investigated as a possible cancer treatment, because of its ability to trigger that protein stopping self-destruct mechanism in cells including, of course, cancer cells.


Now, if you ever come across a strychnine tree and yes, there is such a thing, my advice is to stay as far away as possible. It's native to India and South-East Asia and its bark contains a poison called brucine, but the real lethality comes from the tree's round, green to orange fruit, which contains the alkaloid strychnine. Tests on both sad pigeons and rats have pegged the LD50 for strychnine at about three and fourteen milligrams per kilogram when taken orally, which puts it in a similar category of lethalness as ricin. But the threat here is a neurotoxin that affects the nerves in the spinal chord that control muscle contraction. Essentially it blocks the chemicals that control nerve signals to muscle. By block that chemical, strychnine puts your muscles in a state of constant stimulation, causing seizures until the point of exhaustion and respiratory failure in as little as thirty minutes. This does not sound like a pleasant way to die.


Finally no roster of natural poisons would be complete without a visit to the kingdom fungi, because although few of its thousands of species are poisonous, some of the ones that are contain toxins that would give botulism a run for its money, called amatoxins.

The two most dangerous of these mushrooms contain the most lethal poison of its kind called amanitin and they have the not-so-cryptic names of 'death cap' and 'destroying angel'. The oral LD50 of amanitin-containing mushrooms is between 0.1 and 0.2 milligrams per kilogram, so we're talking at least thirty times deadlier than strychnine.

Amatoxins are essentially rings of amino acids that interfere with enzymes that, again, are responsible for the production of life-giving proteins in your cells, but here they specifically target your liver and kidney cells. Part of why they're so dangerous is that symptoms are delayed for six to twenty four hours after ingestion, so victims only know there's something wrong when their liver and kidneys begin to fail, causing vomiting and diarrhea, which is often mistaken in emergency rooms as the flue, another reason the poisoning is so often fatal.

Most of these deaths in the US are from the misidentification of mushrooms by immigrants from Asia where these particular species of fungi don't exist and instead have quite edible look-a-likes. In cases that are caught early enough, massive doses of milk thistle extract can stop the worst of the damage. The extract contains chemicals that block the uptake of the toxin in the liver cells. But in the worst cases the victim can only be saved by a liver transplant.


I should probably stop, now that I'm just completely paranoid about everything from strange men with umbrellas to all of the formally beautiful mushrooms in the world. The good news is that scientists and lab mice have been working hard at developing antitoxins to these most poisonous natural substances so that, if we do come across one of them, we might not die. And in a very few cases these terribly toxic substances may even be used to save us one day by targeting cancer cells.



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