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Curare, known as "flying death," was used for centuries to make poisoned arrows. Scientists discovered how to use it to create life saving medical treatments that we still use today.

Hosted by: Michael Aranda
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Sources:

http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0706404/abstract
http://www.sciencedirect.com/topics/page/Curare
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sciencedirect.com/science/article/pii/B9780123864543004826
http://www.med.uottawa.ca/historyofmedicine/hetenyi/milner.html
http://nickalls.org/dick/papers/anes/curare1985a.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2312021/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1279945/
http://neuroscience.uth.tmc.edu/s1/chapter04.html
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*Intro music*

Hundreds of years ago, European explorers discovered South American tribes that hunted with poison-tipped arrows.

This killing concoction went by many names, like curare, and flying death. Although it probably tasted terrible, eating curare didn't do a thing.

The poison had to get into an animal's bloodstream, and then it paralyzed skeletal muscles, the type that help you move and breathe. But eventually, research into "flying death" lead to the anesthesia we use during surgeries today. Reports of curare can be traced back to the 1500s, but it took a few centuries to figure out how it worked. In the early 1800s, for instance, some naturalists injected curare into leg muscles of three different donkeys to see what would happen.

That's how you did science back in the day. One donkey died within minutes. The second had a tourniquet on its leg to control its blood circulation, and survived a little longer, but eventually died.

But the third donkey had bellows attached to a tube to pump air into its lungs until the curare wore off, so it survived. With this kind of limited understanding, by the mid-1800s, some physicians were using crude curare extracts, to treat severe muscle spasms, caused by diseases like tetanus or rabies. They also used curare to stop back-breaking convulsions in shock-therapy patients.

But it wasn't very popular in the medical community. There was no standard way to make the stuff, so each batch was a gamble. Different South American tribes even had their own recipes for the dark resin.

All of them involved plants, although poison from frogs or snakes were sometimes mixed in for extra "oomph." In Peru and Ecuador, they used vines of Chondrodendron tomentosum, while in Guyana or Venezuela, their plant of choice was Strychnos toxifera. By 1935, a scientist in Great Britain used museum samples of curare to isolate the main active ingredient from these plants, and called it tubocurarine. Chemically, it's an alkaloid, one of many compounds that contains nitrogen and can affect our bodies, like morphine, caffeine, or quinine. Some of these have had major roles in medicine as well.

Because tubocurarine is a bulky molecule, it can't be absorbed through your digestive system, like some of these other alkaloids. It needs to get into your bloodstream directly to do anything. And in 1936, other British researchers figured out exactly what tubocurarine does: it's a neuromuscular blocking agent, which screws with the chemical messages that get sent between nerves and skeletal muscle cells.

Specifically, it interrupts the binding of a chemical called acetylcholine. Normally, acetylcholine binding sets off a chain of events that let certain charged ions cross muscle cell membranes, which generates an electric current, and makes a muscle contract. But tubocurarine competes for the same receptors that acetylcholine needs to do its job. Your nerves aren't harmed, but your muscles can't move, which is perfect for a surgeon who doesn't want a patient twitching in the middle of an operation.

Because the skeletal muscles in your limbs and around your lungs work a little differently than the smooth muscle in your blood vessels or the cardiac muscles in your heart, curare only affects certain body parts. And the binding of tubocurarine doesn't last forever, so this paralysis can wear off as long as whatever's poisoned can be kept breathing, so it doesn't die, like those two donkeys did.

In 1938, across the Atlantic Ocean, an American brought around 11 kilograms of curare paste back to the US. He hoped that the samples would help a drug company find a cure for his spastic muscle condition. Researchers studied these massive amounts of poison, and ended up creating a synthetic drug called intocostrin, that worked like tubocurarine, to paralyze muscles. With intocostrin in hand, two surgeons in Montreal revolutionized anesthesia starting in 1942.

Generally, anesthesia is a way to make people intentionally unconscious during surgery, so surgeons can operate safely and patients aren't suffering as people are poking around in their bodies. For a while, doctors experimented with a lot of gases to try to knock patients out completely. People inhaled dangerous amounts of chemicals like chloroform, which affects the central nervous system.

But back in 1942, these two surgeons decided to use intocostrin as the muscle relaxing part of the anesthesia equation, and combined it with some inhaled cyclopropane gas. After 25 surgeries went super smoothly, they wrote a paper about this new technique, and it was a pretty big deal. Finally, surgeons could paralyze patients' muscles without all the health risks that come with ridiculous amounts of inhaled anesthesia.

Since then, scientists have made lot of other synthetic chemicals that have muscle-paralyzing effects, although we still haven't found a perfect drug. So, in a weirdly serendipitous way, a poison called "Flying Death" revolutionized anesthesia and made modern surgeries safer than ever before.

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*outro music*