Poisoned by Paleontology

Today's episode is about a toxin so powerful that a little smeared on the tip of a blowgun arrow is enough to silence every muscle in your body, including your diaphragm, stopping your breathing. How did a poison like this become a commonly used drug in modern medicine? 

We'll also go inside a Siberian prison cell where one of the most high-profile political prisoners on the planet collapses and dies. Was this a state-sponsored assassination using a poison from the rainforest?

 Listen to find out. 

Transcript

This is the Pick Your Poison Podcast. I’m Dr JP. ER doctor. Toxicologist, and unapologetic lover of all things poison. Today's episode is about a toxin so powerful that a little smeared on the tip of a blowgun arrow is enough to silence every muscle in your body, including your diaphragm, stopping your breathing. How did a poison like this become a commonly used drug in modern medicine? 

We'll also go inside a Siberian prison cell where one of the most high-profile political prisoners on the planet collapses and dies. Was this a state-sponsored assassination using a poison from the rainforest?

Stay right here to find out.

This is an interactive story. 

Survival isn't guaranteed. 

What happens next depends on you. Will our patient live or die? 

It's up to you and the choices you make. 

So get your gloves on!

It's 8:00 p.m. The Natural History Museum is closed. It's dark and silent except for you because tonight you're living a childhood dream. 

Your friend, a museum curator, has let you in after hours. He is an ethnobotanist studying how plants were used in ancient cultures for medicine, ritual, and sometimes poison.

He's working on a new exhibit called "Medicine from the Amazon". You're there with him behind the scenes. You’ve seen woven baskets still dusted with traces of crushed plants. Ceremonial tools used by shamans. Skulls — with perfectly carved holes drilled into them. Ancient brain surgery. 

You’re favorite part: Images of poison dart frogs. 

Tiny, brightly colored, beautiful and toxic. You learn some new facts to share with your residents during your next lecture.

Across the room, your friend speaks with a colleague, discussing final details like labels and lighting. 

He turns back to you. “Ready for dinner?”

Your stomach growls in response. There's no food allowed in the museum. You're definitely ready.

“Let me grab my bag from the back,” he says. His colleague wants to finish up some work, but will join you in an hour.

Your friend returns, bag over his shoulder. He rubs his hand absently for a moment before buttoning his coat.

You step out into the sharp winter air. The restaurant is only a block away. It's warm and cozy inside; the waitress recognizes him immediately and seats you at his regular table.

He struggles slightly with his coat buttons before pulling it off and draping it over the chair.

He rubs his forehead.

“Phew. I’m exhausted. This exhibit is taking it out of me.” 

You smile. “It’s going to be incredible.”

You notice a small smear of red on his hand and point it out. Blood.

He looks down. “Scratched it grabbing my bag. It’s nothing.”

The waitress appears. “The usual,” she asks? “Gin and tonic? Burger?” 

You say you’ll take the same. The drinks arrive quickly. You talk about opening night plans and media coverage. 

He props his head on his hand again.

“Wow. I’m really tired.”

In the museum, he was energized and animated. 

Now he looks pale.

Drained.

“Just tired?” you ask.

 “Kind of dizzy. My mouth is dry.” He tips back the rest of his drink.

Then he slumps sideways in his chair.

You catch him before he hits the floor.

A man from the next table helps you hold him upright. The waitress calls 911.

You can’t do much else her in the restaurant but hold him up. 

What's happening? He was fine thirty minutes ago in the museum. Fortunately EMS arrives quickly and transports him to the emergency department. This is fiction, so of course you're the doctor. 

The nurses get him undressed, into a gown and onto the monitor. His vital signs are as follows:  98.6 F (37 C), Heart rate 110 beats per minute, Blood pressure 100/50, Respiratory rate is 6, Oxygen saturation is 91% on room air. 

On exam, he's awake and looking at you. He’s having difficulty speaking but appears to understand what you're saying. He manages to convey he feels very dizzy, his limbs feel heavy and hard to move. He also feels short of breath.

On exam, his cranial nerves are intact, meaning he's able to move his eyes, wrinkle his forehead, and smile. His respiratory rate is low, as noted by the vitals signs, but his lungs are clear to auscultation. There’s poor excursion of his chest wall, meaning its not expanding with breaths. His heart is little fast, otherwise unremarkable. No abdominal tenderness. His extremities are significantly weak. He's able to move them, all 4 limbs, but minimally. You ask him to hold up his right arm. He moves it on the bed, but can’t pick it up. You pick it up for him, it thuds back against the bed. He can’t hold it up against gravity. 

Uh, oh. This is pretty worrisome. He's developed significant muscle weakness in less than an hour. Thirty minutes ago, you were leaving the museum. He didn’t have difficulty walking to the restaurant, meaning he was intact at that point. 

Question #1. What’s the first step? 

A.  Obtain more history

B.  Activate the stroke team

C.  Intubate him.

The answer is C. In sick patients, we start with the ABCs. His breathing is at risk. Not only are his extremities weak, his low respiratory rate and poor chest wall movement mean his diaphragm is affected as well. He needs to be intubated before this rapidly progressive weakness leads to complete respiratory failure. The weakness is already reflecting in his low oxygen saturation. 

I personally wouldn't waste any more time, and I'd call for RSI meds, or rapid sequence intubation drugs to get him intubated before the situation becomes worse. You tell him that you're concerned about his breathing and you think he needs to be intubated and put on a ventilator to treat it. His eyes widen, and you can see that he's trying to ask you what's happening, but he isn't able to say very much. The monitor starts beeping. His oxygen saturation is now 89 percent. This is unfolding quickly, and just as you predicted.

There are all sorts of cocktails for RSI, with pluses and minuses to each of the drugs, but in general, we use a sedative plus a paralytic. There are important exceptions, but most of the time, the best way to get the tube through the vocal cords, into the trachea is when the patient is both paralyzed and sedated. You order your favorite cocktail, rocuronium and etomidate. 

You tell the nurse the dose to administer, then get your friend intubated and on the ventilator. You order some basic labs, a chest X-ray to check his lungs as well as the placement of your breathing tube and an EKG. You also order a sedative drip to keep him asleep while the breathing tube is in place. It’s not a good feeling to wake up with a plastic tube jammed down your throat. 

Ok, It’s time to take a few deep breaths yourself. This unfolded extremely rapidly. Now your job is to figure out what the heck happened. Despite what you ordered, its doubtful the answer is in the labs or the chest x-ray. 

You don’t know everything about your friends past medical history, you do know he was fine an hour ago. Essentially, he developed bilateral rapidly progressive paralysis. Could this be a stroke? Or an intracranial hemorrhage. Pretty unlikely, those present with unilateral, one sided symptoms. A head CT is a good idea, but more as a precaution than a definite answer. 

Could he have suddenly developed myasthenia gravis? You've probably heard of it, a rare and unusual disease where the body produces antibodies against itself for elements of the neuromuscular junction. These antibodies keep the muscles from working, resulting in weakness.  It’s not impossible this is a myasthenic crisis, the typical history is weakness that comes and goes, interesting usually worse in the afternoon. Neurology will probably consider this, but you’re friend hasn’t had weakness before, so unlikely. 

We've talked about tick paralysis before, with a bite injecting toxins causing weakness. It can have a fairly rapid onset, though it's usually ascending in nature. In addition, the Natural History Museum isn't out in the country but downtown in a city. Maybe a tick crawled out of one of the exhibits, but again, not likely. 

We talked recently about magnesium, it can cause a rapid onset of weakness, but your friend would have had to have been eating Epsom salts or getting an IV infusion of magnesium while at the museum, again, doesn’t fit here. 

There is one electrolyte disturbance causing dramatic onset of paralysis. That’s question number two. Is it? 

A.                Calcium

B.                 Potassium

C.                 Chloride

Answer: B. potassium. There is something called periodic paralysis, which occurs with dramatic fluctuations in potassium. It's a very rare disease, it can be hereditary. Essentially patients have dramatic fluctuations in potassium, high or low, causing muscle weakness and paralysis. It can be triggered by stress. Maybe the stress of the exhibit opening caused this? His potassium level is pending. 

This is a toxicology podcast, not a neurology one. So let’s focus on poisons. Botulism, we talked about, both infant and food Bourne types. Obviously, causing weakness. Is this botulism toxicity? The onset is actually too rapid. Botulism is fast, but symptoms develop over 12 hours, often more like 24 hours, not minutes. With infant bot, days to even weeks. It causes descending paralysis, and our patient seems to have become weak all over, all at once. Same with Guillian-Barre, not caused by a toxin, but always on the differential for paralysis. 

None of these answers feel particularly satisfying. His results come back, his head CT is normal, his chest X-ray, including your breathing tube, look fine, the tube is in good position. His labs are normal including potassium and magnesium. You consult neurology who recommends more tests including an MRI but the team doesn’t seem to be particularly confident about the diagnosis either.

The nurse wants to know if a visitor can come back. 

“A visitor?" You ask. You haven't even had a chance to find info to contact his family. 

“Sure,” you say. A man enters the room, you recognize him as the colleague your friend spoke to just before you left the museum. You’d completely forgotten he was supposed to meet you at the restaurant. 

He stares in shock at your friend sedated, hooked up to tubes and wires. The man says he finished working, went to the restaurant, heard about the commotion that had happened, realized it was his colleague, and came straight to the emergency department.

You ask him if your friend had been complaining of any medical problems lately or reported any issues. He says no, everyone involved in the exhibit was tired given the heavy workload and long hours, but it was offset by the excitement of digging through archives to find special pieces. 

He asks, “What happened? He was fine at the museum.” 

You explain about onset of rapid paralysis, that the etiology is unclear. He has a surprised expression, then raises an eyebrow. 

"Paralysis?" he says. 

You nod. 

“Paralysis. Like he can’t move his arms and legs?”

“Yes, exactly,” you say. “In the time it took to walk one block.”

He says, "Do you think it was the arrows?" 

“The arrows?” You'd have noticed if your friend was shot with an arrow on the way to dinner. Not to mention you’d have had to dig it out once he got to the ER. 

“Part of the exhibit, is poisoned arrowheads. You know, Amazon plant to modern pharmacology.” He pauses to see if you are following. You aren’t. 

“I had the poisoned arrowheads on the workbench, to label them for the exhibit. Do you think he could’ve touched one? Accidentally?”

Now you are following. This was not on your differential. Not on neurology’s either. 

At the restaurant you noticed a tiny spot of blood on his hand. He said it was a scratch. Not from say a splinter, but perhaps a poisoned arrow? 

“What kind of poison?” you ask. 

“I don’t know, could be anything,” he says. 

“What?” What kind of museum is this? They don’t know what they have?

He sees your frown and says, “I had about 30 different types of arrows out on the table, deciding which to include and working on the labels. 

“How old are they?” Would any poison still be present? Still be biologically active? Could one have caused your friends symptoms? 

“Some are hundreds of years old, others are newer, collected by museum staff on trips to the Amazon and other locations. 

Your brain is racing with questions. Let’s start with first things first. What kind of poisons are on poison arrows? It's a really fascinating topic in my opinion, showing the ingenuity and depth of pharmacologic knowledge present in ancient times. 

Question #3. Toxins from which of the following have been used as arrow poisons?

A.    Plants

B.     Insects

C.     Snakes

D.    All of the above.

Answer = D. all of the above. 

One of the oldest arrows found by archeologists, in South Africa, had residue from a plant called the Bushman’s poison bulb a plant with beautiful pink flowers. These arrows, if you can believe it, are 60,000 years old! Bushman’s bulb is toxic to animals, in humans it causes eye irritation, headaches and may cause hallucinations. 

Snake venom is used to poison arrows. Famously encountered by Alexander the Great and his army in 325 BCE when fighting the Harmatelians then India, now Pakistan, on swords and arrows. Some suggested cobra venom, but modern historians believe Russell’s viper venom fits more closely with descriptions of death. Victims became numb, but also experienced pain and convulsions. Wounds became gangrenous and the victims died a painful death. 

Beetles are used, Diamphidia species. Also in Africa. The larvae are poisonous, not the mature beetles. Symptoms develop over days, not hours. The primary mechanism seems to be red blood cell hemolysis. When red blood cells breakdown, the body can no longer carry oxygen, resulting in death. 

What about poison dart frogs? This is a very timely question. Several toxic compounds are found in them. Two are batrachotoxin, epibatidine. Batrachotoxin causes paralysis and cardiac arrhythmia. You ask if any of the arrows were poisoned with poison dart frogs, he says no those were already in a display case, to be definitely used. Epibatidine is extremely timely and this news came out while I was preparing the podcast. 

If you're a listener, you know about Russians and poison. It's believed Alexy Navalny developed organophosphate toxicity from poison underwear. After returning to Russia, he was imprisoned, and died in prison a year ago in February 2024. According to Russian accounts, he took a walk inside the penal colony, then collapsed and died and was unable to be revived from cardiac arrest. The prison reported that he died from "sudden death syndrome." Undoubtedly true and also completely useless information at the same time.

Recent analysis of blood tubes analyzed in Europe, showed the presence of epibatidine. This compound is found in poison dart frogs in Ecuador and Peru, and is not produced in frogs living in captivity. It's a neurotoxin, causing paralysis and respiratory failure, but in addition, analgesia, thought to be 200 times more potent than morphine. Several European countries concluded that Navalny was murdered by the Russians based on this evidence. An ex-Russian scientist suggested it would've been made in a lab rather than gathered from frogs in the wild.

This could fit with our friends poisoning, but the other curator is clear that these arrows had already been separated. Tons and tons of other stuff can be used as an arrow poison. We could spend all day here, with a lot of things we've touched on another episodes, including digoxin, cardiac medicine and toxin in high doses, strychnine, aconitine. The list could go on forever. But we haven’t mentioned the classic poisoned arrow toxicity, causing paralysis. 

Question #4. Time to pick your poison. Is it? 

A.   Curare

B.   Tetanus toxin

C.   Tetrodotoxin

Answer: A. Curare. All of the above cause flaccid paralysis. It’s curare classically associated with arrows from the Amazon. The word curare originates from the word ourari a Guyana Mukusi Indian meaning arrow poison and further derived from two words put together meaning bird and kill. One of the reasons curare is used as arrow poison is that it doesn’t cause toxicity if ingested. So if you use it during hunting, people eating the animal don’t have risk of toxicity. Its inactivated in the stomach and has to be injected to cause toxicity. 

Death from a curare poisoned arrow would be a bad way to go. It doesn't cross the blood-brain barrier, meaning you’re fully awake, paralyzed unable to move or speak, until you die of respiratory failure. 

Curare is made from vines found in the Amazon. There are dozens of different kinds, often Chondrodendron tomentosum and Strychnos toxifera. Stems and bark are boiled down into a thick paste, then applied to arrow tips. The active ingredient is d-turbocurarine. It was the first paralytic used in surgery in 1942 in Canada. Anesthesia at this time had been around for 100 years. So patients were asleep, but when surgeons cut into muscles, they’d spasm. Sometimes higher doses of anesthesia helped, sometimes thought it killed the patients. For this reason, the abdomen could be difficult to close at the end of a procedure. Curare was used first in a appendectomy, preventing abdominal muscles spasm, allowing easy closure of the wound. It was also used during ECT, electroshock therapy to prevent broken bones and joint dislocations. 

We use paralytics frequently in the ER, for intubation and sometimes in the ICU for paralysis. These days we use derivatives of curare, like rocuronium and vecuronium. Uh oh, during intubation we gave him rocuronium. We gave a paralytic to an already paralyzed patient. Did we make him worse? Fortunately no, because we intubated him so no harm done.

How does curare work? It binds to acetylcholine receptors in the neuromuscular junction, block Ach, meaning the muscle can’t contract, resulting in flaccid paralysis. 

Question #5. Is there an antidote for curare? 

A.   Yes

B.   No

Answer: A. Technically yes there is. We can give physostigmine the antidote for anticholinergic toxicity. But I probably wouldn’t give it, even if I had known. Why not? 

First, a quick reminder about how muscles work. An impulse from the nerve causes release of acetylcholine into the neuromuscular junction. This crosses over and binds to the muscle cell membrane causing depolarization and muscle contraction. Curare binds to the nicotinic receptors where acetylcholine normally binds, blocking the signal to contract and causing flaccid muscles. Physostigmine is a cholinesterase inhibitor, meaning increased acetylcholine, meaning increased muscle contraction.

What’s the dose of physostigmine to reverse curare? No idea. What are the side effects? Physostigmine causes cholinergic effects including nausea, vomiting, diarrhea, and the killer B’s bradycardia, ie slow heart rate, bronchospasm and bronchorrea. It’s toxic in and of itself. If you remember it’s naturally occurring in the Calabar bean, used as a trial bean for witchcraft trials. I have no idea the dose for curare overdose, because, of course, we have no idea of the amount of curare exposure. There’s probably someone out there arguing for physostigmine before intubation. I’m picturing trying to calibrate it to the right dose and see-sawing back and forth between curare toxicity and physostigmine toxicity. Intubation is safer, guaranteed to work until the curare wears off. 

Modern day paralytics used in the OR have a modern antidote frequently used by anesthesia, at the end of an operation, for example. It’s called sugammex and it reverses several paralytics. It has a donut shape and once given, holds vec and panc inside, inactivating them. 

Ok, back to our patient. His colleague agrees several of the arrows were tipped with curare. By intubating our friend and putting him on the ventilator, we’ve safely treated him until the curare wears off. How long will it last? It’s a quick on, quick off drug. One of the reasons it was popular in medicine. It can last for as short as 20-30 minutes. You speak to the intensivist. She says she’ll leave the sedation on for a total of two hours, to avoid the risk of having him paralyzed but awake, then come to the ED to access him.

 I have to share this crazy story I came across during research for this episode about a plot to kill Lloyd George the British prime minister during WWI. A family of contentious objectors, one of whom owned a chemist shop, decided to try to assassinate him with curare. Unbeknownst to the family, a government spy infiltrated the plan. In fact, the spy was given the job of shooting Lloyd George on a golf course with an airgun containing curare pellets. Crazy plan, fortunately stopped by the authorities. 

            The ICU doctor comes down, turns off sedation and re-examines your friend. He’s awake and moving. She decides he meets extubation criteria and extubates him in the ED. He not only recovers without sequelae, he doesn’t even get admitted to the hospital, but discharged after a period of observation. He says his hand must’ve brushed against something sharp while grabbing his bag. Hungary, he dismissed it as a small scratch, not realizing a poison arrow was the culprit. 

            This is a fictional case, but it is based on real poisonings. Particularly one published by a curator at the NY Botanical Garden, who accidentally stabbed himself with a curare dart while cleaning out his personal collection. How do we know this? He published the account in a medical journal. 

            Last question in today’s podcast. Curare has been used to treat which other poisons? 

A.    Strychnine, 

B.     Tetanus, 

C.     Rabies, 

D.     All of the above.

Follow the Twitter and Instagram feeds both @pickpoison1 for the answer. Remember, never try anything on this podcast at home or anywhere else. 

Thanks for listening. It helps if you subscribe, leave reviews and/or tell your friends. Transcripts are available at pickpoison.com. 

            While I’m a real doctor this podcast is fictional, meant for entertainment and educational purposes, not medical advice. If you have a medical problem, please see your primary care practitioner. Until next time, take care and stay safe.

The answer is A and B, strychnine and tetanus. As I'm sure you know, these cause serious muscle spasms. It therefore makes sense that curare was used in an attempt to relax these muscle spasms.