The accidental rise of Botox

Summary

Podcast Summary: Unexplainable – "The Accidental Rise of Botox"
Date: March 18, 2026
Host: Sally Helm, with guests Jean Carruthers (Ophthalmologist/Dermatologist), David Simpson (Neurologist), Axel Vollmer (Psychiatrist)

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Overview

This episode of Unexplainable delves into the surprising medical journey of Botox—a poison-turned-miracle drug that began its infamy causing deadly paralysis and now treats everything from wrinkles to migraines, excessive sweating to potential depression, and perhaps even cancer. The host, Sally Helm, personally recounts experiencing a medical, non-cosmetic use of Botox, setting the stage for an exploration into how a notorious toxin became a multi-use staple of modern medicine.

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Key Discussion Points & Insights

1. Personal Introduction to Botox’s Medical Side

• Sally Helm’s Experience: Sally discusses her procedure to treat a life-long inability to burp by injecting Botox into her throat, highlighting its effect—selective local paralysis (01:10).
• Widespread Uses: Beyond cosmetic applications, Botox is used for migraines, excessive sweating, and investigative treatments for depression.

2. The Origin Story: From Sausage Poison to Medical Marvel

• Botulism’s Discovery
  • Early 1800s, Germany: Justinus Kerner, a polymath doctor and poet, investigates outbreaks of food poisoning from dirty sausages—botulism—resulting in deadly paralysis (04:06).
  • Kerner self-administers the toxin, noting its effect on salivary glands, leading to the first insights into dose-dependent toxicity (06:03).
    • Quote: Jean Carruthers (on Kerner’s experiment): “He tried it himself. He put some of those fatty substances that they had ingested into his own mouth against the advice of his friends.” (05:53)
  • Paracelsus’s famous maxim is invoked: “All things are poisonous and nothing is without poison. Only the dose permits something not to be poisonous.” (06:53)

3. Turning Point: Scientific Isolation and Therapeutic Exploration

• Isolation for Research and Warfare
  • WWII research isolates the toxin due to its potential as a weapon; post-war, Dr. Ed Schantz supplies it to other scientists (08:06).
• First Medical Uses
  • Dr. Alan Scott explores Botox as a therapy for strabismus (crossed eyes) and later blepharospasm (eye twitching) (08:21).
  • Jean Carruthers joins Scott’s research, witnessing game-changing results for patients with uncontrollable eyelid spasms (09:06).

4. The Cosmetic Leap: From Medical to Mainstream

• Serendipitous Discovery
  • A blepharospasm patient points out her smooth brow after treatment, sparking the idea for cosmetic use (09:44).
  • Quote: Jean Carruthers: “[The patient said] every time you treat me there, I get this beautiful untroubled expression. Now this is when the penny dropped because I happened to have the perfect husband.” (09:44)
• Early Skepticism and Self-Experimentation
  • Public resistance to cosmetic Botox due to its poisonous reputation— overcome by Carruthers self-injecting and showing before/after results (11:45).
    • Quote: Jean Carruthers: “I make a joke of it. Now, I haven’t frowned since 1987, but that’s how I got 18 patients into our study.” (11:45)

5. Botox Goes Mainstream—and Global

• Patents and Production
  • Scott and the Carrutherses sell patents to Allergan, leading to mass-market cosmetic use (12:28).
  • High-security, secretive manufacturing process described (12:58).
• A ‘Magical’ Drug in Public Perception
  • Quote: Jean Carruthers: “Maybe it’s sort of like fairy godmother discovering that you can do something magical with it. It’s now such a magical new drug with so many uses.” (13:35)

6. Expanding the Medical Frontier

• Increasing Medical Indications
  • Dr. David Simpson describes widespread adoption across specialties: neurology, dermatology, ophthalmology, gastroenterology, urology, and more (17:47).
  • Notable conditions treated include spasticity, hyperhidrosis (excessive sweating), overactive bladder, and the unexpected discovery of efficacy in migraine treatment (19:38).
    • Quote: Simpson: “If it moves, botulinum toxin can stop it. And actually, we now extend that to if it hurts, then botulinum toxin may help relieve the pain as well.” (20:20)

7. Mechanisms and Risks

• How It Works
  • Inhibits neurotransmitter release, leading to selective local muscle paralysis and also blocking pain chemicals (20:40).
• Risks and Warnings
  • Black box FDA warning for rare, but serious, side effects—most risks relate to local muscle weakness or toxin spread (21:48).
    • Quote: Simpson: “There’s really a skill set that needs to be learned. In fact, I usually encourage doctors to find a mentor to train them properly. Almost like surgery.” (21:48)

8. Medicine by Serendipity

• Serendipitous Innovation
  • The role of doctor/patient observation and creativity in finding new uses—medicine as both art and science (22:44).
  • Impressive flexibility: “Swiss Army knife” in medicine (20:40).
• Current Approvals and Off-label Use
  • Nine official FDA-approved uses; many more used off-label, sometimes with limited understanding of the mechanism (20:40).

9. The Depression Question & the Facial Feedback Hypothesis

• Experimental Antidepressant
  • Dr. Axel Vollmer recounts self-experimentation with Botox injections for depression, describing a personal sense of “Teflon” resilience (23:51).
    • Quote: Vollmer: “An injection of resilience, so to speak.” (23:51)
• The Theory: Charles Darwin’s work and the facial feedback hypothesis: lack of frowning/muscle movement may trick the brain into mood improvement (25:16).
  • Quote: Vollmer: “If you're angry, you frown. And this frowning communicates your anger to others, but it also communicates this anger to yourself.” (25:16)
  • Multiple studies suggest efficacy; a large RCT is still needed (26:32).

10. Future Frontiers

• Beyond the Known
  • Ongoing research: wound healing, pain, even potential application in cancer treatment by disrupting tumor–nerve communication (28:35).
  • Quote: Vollmer: “For me, cancer was the most fascinating new indication. I wasn’t aware of that.” (28:35)
• Enduring Mystery and Medical Potential
  • The episode closes reflecting on Botox’s unlikely journey—from deadly sausage-borne illness to a mainstay of modern therapeutic practice.

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Notable Quotes & Timestamps

• "And if you relax that muscle with Botox, you can burp." — Sally Helm (01:22)
• "He tried it himself. He put some of those fatty substances that they had ingested into his own mouth against the advice of his friends." — Jean Carruthers (05:53)
• "All things are poisonous and nothing is without poison. Only the dose permits something not to be poisonous." — Paracelsus, quoted by Sally Helm (06:53)
• "Every time you treat me there, I get this beautiful untroubled expression." — Jean Carruthers (09:44)
• "If it moves, botulinum toxin can stop it. And actually, we now extend that to if it hurts, then botulinum toxin may help relieve the pain as well." — David Simpson (20:20)
• "For me, cancer was the most fascinating new indication. I wasn’t aware of that." — Axel Vollmer (28:35)

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Timestamps for Important Segments

• [01:10] – Sally’s personal account: using Botox for throat muscle relaxation.
• [04:06] – First description of botulism and Kerner’s self-test.
• [08:21] – Alan Scott’s strabismus research; Jean Carruthers’ involvement.
• [09:44] – Discovery of cosmetic use by accident.
• [11:45] – Early adoption and skepticism; Carruthers’ self-experimentation.
• [17:47] – The explosion of medical uses, described by Dr. Simpson.
• [19:38] – Migraine benefits first noticed.
• [20:40] – How Botox works; breadth of off-label use.
• [21:48] – Safety concerns and training necessity.
• [25:16] – The facial feedback hypothesis and its relation to mood.
• [28:35] – Emerging research: cancer and new frontiers.

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Conclusion

The Accidental Rise of Botox masterfully traces the toxin’s journey from sausage-centric scourge to multi-purpose wonder drug. Through historical anecdotes, personal stories, expert testimony, and lively curiosity, the episode demonstrates how serendipity, experimentation, and a willingness to reevaluate poisons as potential treatments have redefined medical practice—and may continue to do so as Botox’s story unfolds.

Transcript

[Podcast Host / Announcer]

Support for the show comes from Anthropic, the team behind Claude. They say that Claude is the collaborator that actually understands your entire workflow. So for developers that looks like Claude code, it runs in your terminal, reads your code base, and can apparently take on things like writing tests, refactoring or debugging without you hand holding it through every step. Anthropic committed to not running ads in Claude. So when you are deep in something that matters to you, they say the answer you get is shaped by your question, not by an advertiser's agenda. Ready to tackle bigger problems. Get started with Claude today at Claude AI Unexplainable Spring starts at the Home

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[Sally Helm (Podcast Host / Narrator)]

It's unexplainable. I'm Sally Helm and a couple of months ago I was up very early walking down the street in Manhattan. Oh my Lord, there's someone on a 5am run.

[Axel Vollmer (Psychiatrist)]

Wow.

[Sally Helm (Podcast Host / Narrator)]

I was heading to the hospital to get this procedure that would help me learn to burp. Before that I had been a lifelong no burper. You can go back and listen to the whole episode about this if you want, but all you need to know today is that the treatment for this condition involves a drug. A very famous one. I'm getting Botox in my throat and not in like a make my throat look younger kind of way, but like inside my throat. I guess inside it will look very young. Botox has this amazing unusual ability to paralyze a muscle locally, like just the muscle that you inject it into. So in my case, a muscle in my throat was clamping up so that I couldn't burp. But if you relax that muscle with Botox, you can burp. I got the procedure that morning and it worked. Now before this, I had obviously heard of Botox, mostly in a cosmetic context. I am from Los Angeles, definitely a city that believes wrinkles are optional. I also knew that it is derived from a poison and I found myself wondering just more and more about the bizarre journey that this toxin has taken in the world. Because as I started telling people that I had gotten Botox, they started telling me that they had gotten Botox for wrinkles. Some of them, yes, but also for migraines, for excessive sweating. It's even being studied as a treatment for depression. And I wanted to know, how did we figure out that it can do all that? Like, who looks at a toxic, toxic poison and sees a medicine? And what else might this weird little wrinkle cure, say, someday be able to do? The story begins in the early 1800s. In the German countryside, people are coming down with a mysterious illness. I heard about it from Dr. Jean Carruthers. She knows this story because Botox will become very important in her career. And when these Germans got sick, their eyelids would droop, their speech would slur,

[Jean Carruthers (Ophthalmologist / Dermatologist)]

they have a descending paralysis of their face and then of their diaphragm. Essentially, their diaphragm stops working, and so they no longer can live.

[Sally Helm (Podcast Host / Narrator)]

There's a young, newly minted doctor living nearby, Justinus Kerner. And he is called in to investigate. Justinus Kerner had decided to become a doctor after he awoke from a prophetic feeling dream to find that a paper prescription from a nearby hospital had wafted in through the window while he was sleeping. And he was like, it's a sign. He became a doctor. He also later became famous as a romantic poet. And he has a wine named after him.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

I've tasted it. It's very delicious. He was a true polymath. He had in his house all kinds of contraptions that were sort of magical. But anyway, going back to the 1820s, Justinus Koerner did his medical thesis on

[Sally Helm (Podcast Host / Narrator)]

these poor people, these people in the German countryside who were struck by this mysterious paralysis. He documents a pattern. All the patients seem to have eaten the same food.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

They made sausages. And the sausages maybe weren't totally clean. You know, maybe there was dirt in the sausages.

[Sally Helm (Podcast Host / Narrator)]

Food safety standards in this region at this time have kind of gone down. It's the aftermath of the Napoleonic Wars. Things are rough, and one result is these unhygienic sausages.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

And so the disease itself, this mysterious paralytic disease, became known as botulism because botulus is Latin for sausage.

[Sally Helm (Podcast Host / Narrator)]

Okay, so Justinus Kerner, this polymath, winemaker, poet, physician, he describes these symptoms in detail. And he does one other surprising thing.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

He tried it himself. He put some of those fatty substance that they had ingested into his own mouth against the advice of his friends.

[Sally Helm (Podcast Host / Narrator)]

Why did he do that?

[Jean Carruthers (Ophthalmologist / Dermatologist)]

Because he wanted to know. So his mouth became dry. This is the first instance that anyone had shown that a toxin could stop the activity of your salivary glands.

[Sally Helm (Podcast Host / Narrator)]

Hmm.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

Wow.

[Sally Helm (Podcast Host / Narrator)]

I mean, it just seems so, so reckless to do when he knew that it had killed people. What do you make of it?

[Jean Carruthers (Ophthalmologist / Dermatologist)]

I think that he just had a little taste. I think he was a very smart man. He didn't eat the whole sausage because he had this idea and all these people are paralyzed. Maybe there's something in this where we could use whatever it is to treat people who have overactive muscle conditions. He saw the other side of the poisoning as a potential treatment. It was brilliant.

[Sally Helm (Podcast Host / Narrator)]

I have an instinct here to be like, that is poison, Justinus. Do not put that in your mouth. But he did have some reason to think that this could be okay. Another doctor had actually written this idea down a couple hundred years earlier. Paracelsus, the father of toxicology, he wrote this famous line that kind of sounds like a what is there? That is not poison. All things are poisonous and nothing is without poison. Only the dose permits something not to be poisonous. Kerner sees early that botulinum toxin could be the poster child for this idea that in small doses it could be useful to medicine. But no one really picks up on that thought for another hundred plus years. We did figure out some stuff about how to prevent botulism. And then During World War II, the US is worried that Germany and Japan are going to develop botulinum toxin as a biological weapon. So they get a whole bunch of researchers together to study it and look at antidotes. One of them, a guy named Ed Schantz, is able to isolate the toxin from the bacterial sludge that it grows in. After the war, he makes a whole batch of it in his lab in Wisconsin.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

And he was actually quite noble and supplied it to people who were wanting to do research on botulinum toxin. And he sent, I think, 100 milligrams to Alan Scott.

[Sally Helm (Podcast Host / Narrator)]

Alan Scott is an ophthalmologist, and he has this idea that botulinum toxin could help cure strabismus, that condition where one eye turns in. He thinks if you weaken the muscle that's pulling on that eye, you could cure this condition without surgery. He does some experiments and it works. And this is where Gene Carruthers enters the story.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

I was a pediatric ophthalmologist at the University of British Columbia in Vancouver, and I started reading about it and it got really fascinating.

[Sally Helm (Podcast Host / Narrator)]

So she gets herself a fellowship with Alan Scott. He's now investigating another use Maybe botulinum toxin can treat a condition called blepharospasm.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

These poor people, they can't count on their eyes opening, their eyes, spasm shut, so they can't drive a car, they can't cross the street on their own, they can't hold down a job. And after they've been treated with botulinum toxin, they can drive a bus with hundreds of other people in it. I mean, it's a total game changer.

[Sally Helm (Podcast Host / Narrator)]

Allen teaches Jean how to inject this toxin. She starts treating blepharospasm patients at her clinic in Canada. And one day during treatment, one of those patients gets mad.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

She said, you didn't treat me here between her eyebrows. And I apologized to her and I said, I'm sorry, I hadn't thought you were spasming there. And she said, oh, I'm not spasming there, but every time you treat me there, I get this beautiful untroubled expression. Now this is when the penny dropped because I happened to have the perfect husband.

[Sally Helm (Podcast Host / Narrator)]

Jean's perfect husband, Alistair, is a dermatologist and she has heard him complain about how difficult it is to treat those frown lines between the eyebrows, the 11. A lot of people want them gone, but the best treatment at the time doesn't really work, can't even be dangerous. So Jean goes home and over dinner she tells Alistair that she has this idea. Botulinum toxin could solve that problem. You freeze the underlying muscle, you get rid of the wrinkles. He is interested and they put together a study to test it. They need 18 patients to sign up and that is not happening.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

Most people in the world were running a mile from it. They were, no, that's a terrible poison. I don't want to have that injected. And it's a cosmetic treatment. Everyone thought we were over the edge, crazy.

[Sally Helm (Podcast Host / Narrator)]

They finally find one person who has had enough up close experience to know that this drug is not going to kill you. And that is Jean's receptionist, Kathy Bickerton Swan.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

She had sat there for four years watching all my research patients coming in, out, always happy, always polite, always grateful. And so when we said, kathy, how would you like to be part of the study? She said, yeah, whatever, you know, it was no big deal to her.

[Sally Helm (Podcast Host / Narrator)]

And then Jean pulls a Justinus Kerner. The second cosmetic patient that she treats is herself. Her husband gives her the injection. It's the first cosmetic treatment she has ever gotten. But she's sold.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

And I make a joke of it. Now, I haven't frowned since 1987, but that's how I got 18 patients into our study. They would say, no, it's a poison. And I would say, well, what do you think? And I'd show them my frown line picture from before and my brow.

[Sally Helm (Podcast Host / Narrator)]

Now, eventually, as we all know, way more than 18 people try cosmetic Botox. Well, girls, we've done it. We're now international champs when it comes to Botox. People are paying good money these days to be injected with food poisoning, or at least a form form of it.

[Podcast Host / Announcer]

Mark Twain said wrinkles should merely indicate where smiles have been. He didn't know about Botox.

[Sally Helm (Podcast Host / Narrator)]

Alan Scott had sold his initial patent to a pharma company called Allergan that mostly did eye care. The Carruthers sell them a patent, too. Botox, by the way, is actually just one of the brand names for botulinum toxin. It's like how we call all tissues Kleenex. Now. Gene also makes money on this, including by doing research and consulting for the pharma company. And the old sausage poison goes totally mainstream. It has a whole life that Justinus Kerner could never have foreseen.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

Botox is now made in California at an undisclosed location and flown in a private jet with guards to the bottling plant, where it is made into the Botox vials that are shipped around the world.

[Sally Helm (Podcast Host / Narrator)]

This stuff is still poisonous at large doses. Don't want that plane getting hijacked, so. And things can very occasionally go wrong with cosmetic Botox, especially if you get it from a bad injector. But for Jean, obviously, it's been a good thing. I mean, she hasn't frowned since 1987. I've seen you called the godmother of Botox. Why godmother?

[Jean Carruthers (Ophthalmologist / Dermatologist)]

Well, I guess, I don't know. Maybe it's sort of like fairy godmother discovering that you can do something magical with it. It's now such a magical new drug with so many uses.

[Sally Helm (Podcast Host / Narrator)]

Botox made this jump from ophthalmology to dermatology, but soon enough, it jumps again when dermatologists and other doctors begin to notice that it might be able to treat all kinds of conditions that we previously had no way to cure. That's after the break.

[Podcast Host / Announcer]

Support for the show comes from Anthropic, the team behind Claude. If you are the kind of person who goes down a rabbit hole and then stays there, or who keeps pulling at a question until it clicks, they say Claude was built for that kind of thinking. For developers, that looks like Claude code. It runs in your terminal, reads your code base, and can apparently take on things like writing tests, refactoring or debugging without you hand holding it through every step. I texted my friend who uses Claude and told him I was making an ad about Claude and asked why I should use Claude and or Claude code. It's just really good at coding lol he said. What does that mean? I said with it I can build things. I wouldn't have time for myself or ability for myself in many cases, he said. Nice, I said. Anthropic says they are committed to not running ads in Claude. So when you are deep in something that matters to you, they say the answer you get is shaped by your question, not by someone else's advertisement taking you out of the deep work ready to tackle bigger problems. Try Claude for free at Claude AI Unexplainable and see why some problem solvers choose Claude as their thinking partner

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[Charlie Cox (Actor)]

Hi everyone, I'm Charlie Cox. Join us on Disney as we talk with the cast and crew of Marvel Television's Daredevil Born Again.

[Sally Helm (Podcast Host / Narrator)]

What haven't you gotten to do as

[Commercial Narrator (Home Depot)]

Daredevil Be in the Avengers, Charlie and

[Sally Helm (Podcast Host / Narrator)]

Vincent came to play.

[Jean Carruthers (Ophthalmologist / Dermatologist)]

I get emotional when I think about it.

[Charlie Cox (Actor)]

One of the great finales of any

[Sally Helm (Podcast Host / Narrator)]

episode we've ever done.

[David Simpson (Neurologist)]

We are gonna play Truth or Daredevil.

[Axel Vollmer (Psychiatrist)]

What? Oh, boy.

[Sally Helm (Podcast Host / Narrator)]

Fantastic.

[David Simpson (Neurologist)]

You guys go hard, man.

[Charlie Cox (Actor)]

Daredevil Born Again Official podcast Tuesdays and stream season two of Marvel Television's Daredevil Born Again on Disney.

[Sally Helm (Podcast Host / Narrator)]

Oh, it tastes sweet. Her boy's in. Yeah. It's not as if you ingested a lethal amount. If I have a patient that comes in, they're 18 years old, they don't have any lines, I might say, you know what? Why don't you wait a couple years and come back? Let's start here. Maybe this is a really hard one, but can you do your best to give me a list of of all of the conditions that botulinum toxin is used to treat?

[David Simpson (Neurologist)]

That would take probably much longer than we have time to do.

[Sally Helm (Podcast Host / Narrator)]

David Simpson, neurologist and to be fair, I had a hard time even finding a list of all of the uses that this toxin now has in medicine.

[David Simpson (Neurologist)]

It's really used by almost every field in medicine, from neurologists like me to dermatologists, plastic surgeons, ophthalmologists, gastroenterologists, urologists, and on and on.

[Sally Helm (Podcast Host / Narrator)]

David himself first uses this toxin back in the early 90s. So just a little while after Jean makes her wrinkle discovery, he is treating a patient with a traumatic brain injury who has what is called spasticity. In one of his arms, the muscles tense up.

[David Simpson (Neurologist)]

The elbow was flexed, it was crunched up like a pretzel, and he developed a large calcium deposit in the inner elbow.

[Sally Helm (Podcast Host / Narrator)]

He needed surgery to fix this, but his surgeon couldn't get the arm to relax. So he goes to David and he

[David Simpson (Neurologist)]

and I discussed this very new medicine, and he said, what if we inject it into the muscles of the upper arm so we could relax the elbow? There was no reports of it done at that time, and so we got approval from the medical board for use. We injected into this patient, and he responded nicely and the arm opened up.

[Sally Helm (Podcast Host / Narrator)]

Over time, as doctors get more and more confident with this drug, they also get more and more ideas for what it could do. The company that makes botox obviously wants it to be used for more conditions. David, by the way, has done consulting for that company and gotten research grants from them. And as time goes on, that company starts testing, doing trials. The drug works for various movement disorders. It also works on hyperhidrosis or excessive sweating. They try it on overactive bladder, where you have to pee like 50 times a day, it helps those patients, too. And meanwhile, the cosmetic use is picking up steam. And there's a plastic surgeon out in

[David Simpson (Neurologist)]

Beverly Hills who was injecting individuals for their wrinkles cosmetically. And the individuals he was treating for wrinkles came back and said, you know, my migraines are less. And that led to studies in migraine that ultimately received an FDA approval and widely used today.

[Sally Helm (Podcast Host / Narrator)]

We don't totally know what causes migraines. Especially back then, we didn't have a lot of good treatments. And it wasn't clear exactly why this toxin could help, but. But it did. An early idea was maybe it's relaxing the muscles in your head, because that's generally what this drug does. It stops muscles from moving.

[David Simpson (Neurologist)]

One of the adages I often use to describe the indications is if it moves, botulinum toxin can stop it. And actually, we now extend that to if it hurts, then botulinum toxin may help relieve the pain as well, because that's an emerging area of use.

[Sally Helm (Podcast Host / Narrator)]

This toxin basically stops nerves from secreting chemicals, neurotransmitters, especially one major neurotransmitter that's key for telling muscles to move, but also, it turns out, other neurotransmitters that can make us feel pain. That's probably roughly how it works for migraine. This toxin affects just a really fundamental process in our body. That, plus the fact that you can use it so locally, like just inject it into the one muscle that you want to treat, that makes it into this little medical Swiss army knife. Today, it is officially approved for nine different medical problems, and it is used off label for many, many more. Like my burping, off label means it's for a use that the FDA hasn't officially approved. Now, obviously, no drug is perfectly safe, and this one comes from an extremely poisonous poison. There are some dangers here. In fact, in 2009, the FDA put a black box warning on this drug and others like it, a reminder that they can cause serious complications, including difficulty breathing.

[David Simpson (Neurologist)]

Now, that's extremely rare in the doses we use, but the more common concern is that in the process of causing localized muscle weakness, which is what we're trying to do, it can cause excess weakness of the muscle you're injecting, or it can spread to other muscles. For example, if you're injecting a patient with facial spasm around the eye and the botulinum toxin spreads to the muscle that keeps the eyelid open, you can get a droopy lid. And so there's really a skill set that needs to be learned. In fact, I usually encourage doctors to find a mentor to train them properly. Almost like surgery. I often say there's a lot of science in the field, but there's also a lot of art that needs to be passed through the generations.

[Sally Helm (Podcast Host / Narrator)]

It's interesting to me how it kind of travels through medicine. It's like a doctor notices something, a patient notices something. People experiment. It all feels sort of much more, I don't know, kind of ad hoc and creative that I think we're used to thinking of it well.

[David Simpson (Neurologist)]

I think one of the lessons we learn is to be open to serendipity and to be creative in pursuing new indications that others may not have thought about or pursued. There's an interesting emerging literature on depression.

[Sally Helm (Podcast Host / Narrator)]

Hmm.

[David Simpson (Neurologist)]

Certainly I would put that into one of the categories of one of the mystery uses that we don't quite understand.

[Axel Vollmer (Psychiatrist)]

For me, it was really striking how immediately the psychotropic effect occurred.

[Sally Helm (Podcast Host / Narrator)]

Axel Vollmer is a psychiatrist and he has studied the question of whether botulinum toxin can help with depression. We'll get into that. But at a certain point in his research, he got curious enough to try it himself. So we had a colleague inject him right between the eyebrows.

[Axel Vollmer (Psychiatrist)]

On those frown lines, it was a little bit painful. The pressure of the fluid in the tissue, it's not very pleasant feeling. But then it took a couple of days until the muscle relaxing effect set in. And I have four children and it's very crowded and noisy and busy at home. And it was just like a layer of Teflon covering it just didn't bother me the way it sometimes does. An injection of resilience, so to speak.

[Sally Helm (Podcast Host / Narrator)]

Axel would be the first to say that he is not actually a good test subject for himself, because he went into this with a theory. It goes back actually to a very old idea. Charles Darwin wrote about it in one of his lesser known works called the Expression of Emotions in man and Animals. That came out a little over a decade after his real banger, on the Origin of Species. In his other book about emotions, he talks about how our facial expressions are tied to what we feel. Those muscles that make your eyebrows contract and cause those frown lines, he calls them the grief of muscles. People build on this idea and come up with something called the facial feedback hypothesis.

[Axel Vollmer (Psychiatrist)]

If you're angry, you frown. And this frowning communicates your anger to others, but it also communicates this anger to yourself.

[Sally Helm (Podcast Host / Narrator)]

And is this a proven idea or it's just.

[Axel Vollmer (Psychiatrist)]

Yeah, no, it's a. It's a very old hypothesis. And it has been proven, proven experimentally time and again, that it's not just

[Sally Helm (Podcast Host / Narrator)]

that I'm happy, I smile. Also, if I smile when I'm not feeling happy, I start feeling happy.

[Axel Vollmer (Psychiatrist)]

Take it till you make it.

[Sally Helm (Podcast Host / Narrator)]

So, a while back, Axel and one of his colleagues got curious about botulinum toxin as a treatment for depression because it freezes your frown lines, and that's where you express all this negative emotion. So, per the facial feedback hypothesis, if you make Browning impossible, you should feel better. They looked into it and found that a dermatologist in the United States had actually already done a study on this with promising results. Axel did his own small study, a randomized controlled trial. It also suggested that Botox could work as an antidepressant. Then other researchers got in on this.

[Axel Vollmer (Psychiatrist)]

There were several independent replications of our findings that uniformly confirmed this effect.

[Sally Helm (Podcast Host / Narrator)]

Axel, by the way, also did some consulting for the company that makes Botox along the way here. And he told me there still needs to be a large randomized controlled trial to really be sure that this effect is a thing. But even if it is true that botulinum toxin can work as an antidepressant, we still don't know why. We don't know if it is because of the facial feedback hypothesis. There is some evidence that small amounts of Botox could travel into the central nervous system. Axel thinks it would be too small to really do anything, but it's possible that it has some antidepressant effect that we don't understand. There's also an interesting study Axel was involved in that looks at people who had gotten either Botox or other treatments for conditions like migraine, excessive sweating, and spasms. And it found that overall, people who were treated with Botox for any of the conditions they looked at were less likely to report depression.

[Axel Vollmer (Psychiatrist)]

So maybe you can. You can inject it into your butt or into your thigh or whatever.

[Sally Helm (Podcast Host / Narrator)]

You'll be so happy.

[Axel Vollmer (Psychiatrist)]

Yeah, and. And this is, of course, this is. This is really intriguing, but on the other hand, we. We don't want to do this study because it leads us too far away from what we know is working.

[Sally Helm (Podcast Host / Narrator)]

He said first they want to do the big trial to confirm that these frown line injections really, really work. And his money is still on the facial feedback hypothesis. He said the most likely explanation for that other finding is just that Botox works really well as a treatment in general. So maybe that is why patients report less depression when they get it, because their excessive sweating or their migraines really improved. This toxin has a lot of uses and we are still finding more. Axel told me he went to a conference recently. It was called toxins 2026 and there were presentations on botulinum toxin and wound healing. Botulinum toxin and pain.

[Axel Vollmer (Psychiatrist)]

For me, cancer was the most fascinating new indication. I wasn't aware of that.

[Sally Helm (Podcast Host / Narrator)]

Yeah, some new work suggests that nerves might help tumors grow, so using Botox to block those signals might help tumors shrink. Botox to treat cancer? Not a bad journey for one of the deadliest poisons known to man. This episode was produced by me, Sally Helm. It was edited by Joanna Solotaroff with help from Julia Longoria. Mixing in sound design from Christian Ayala. Fact checking from Melissa Hirsch and Sarah Schweppe. Special thanks today to Ed Chapman, Eric finzi and Peter McAllister. Meredith Hoddenott runs the show. Jorge Just is our Editorial director. Amy Padula and Noam Hassenfeld are not experimenting on themselves, unlike many people in this story. And Bert Pinkerton kept thinking about what the doctopus had told her at the station where the sun never shines where the sun never shines. And then it hit her. The deepest station in New York, 190th Street. She needed to get to Washington Heights. Thanks as always to Brian Resnik for co creating the show along with Bird and Noem. And if you out there have any thoughts about the show, please send us an email. We love getting your emails. We are [e-mail] you can also leave us a nice rating or review wherever you are listening right now. That really, really helps. And if you are into supporting the show and all of VOX in general, join our membership program. You can go to vox.commembers to sign up. Unexplainable is part of the Vox Media Podcast Network and we will see you next time.