# The Accidental Rise of Botox  ## Episode metadata - Episode title: The Accidental Rise of Botox - Show: Sidedoor - Owner / Host: Smithsonian Institution - Guests: [Axel Wollmer](https://share.snipd.com/person/9685716b-d657-4b77-a523-de3e9bbe8129), [Jean Carruthers](https://share.snipd.com/person/29158162-c25c-4bb6-8377-157c7b964f5d) - Episode publish date: 2026-09-16 - Episode AI description: Jean Carruthers, an ophthalmologist who pioneered cosmetic Botox, and psychiatrist Axel Wollmer, who studies its potential for depression, trace botulinum toxin’s unlikely journey from sausage poison to modern medicine. They explore its breakthrough in eye care, accidental leap into wrinkle treatment, expanding uses for migraines and muscle disorders, and intriguing research into mood, pain, wound healing, and cancer. - Mentioned books: [On the Origin of Species](https://share.snipd.com/book/39625d0a-d5bb-4200-86f3-7c1ebff9e5a5) by [Charles Darwin](https://share.snipd.com/person/ba790d8f-d07d-4ce1-b986-d6049d349233), [Expression of the Emotions in Man and Animals](https://share.snipd.com/book/ac130976-e36a-44e1-9c60-6a1119a15636) by [Charles Darwin](https://share.snipd.com/person/ba790d8f-d07d-4ce1-b986-d6049d349233) - Duration: 25:16 - Episode URL: [Open in Snipd](https://share.snipd.com/episode/cdcb988e-885f-4321-829d-47dd7cab622c) - Show URL: [Open in Snipd](https://share.snipd.com/show/fa9f2106-4050-4379-b8f0-ab3877b94867) - Export date: 2026-09-21T13:40:55 ## Snips ### [The Doctor Who Tasted Sausage Poison](https://share.snipd.com/snip/7d7f8a56-b7e1-4288-8240-c8b789182a95) 🎧 04:05 - 07:56 (03:51) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/508319cc-f645-4900-8c45-1474b1cc2c08" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Justinus Kerner investigated paralysis linked to contaminated sausages and identified botulism’s effects on salivation and muscles. - He tasted the suspected toxin himself, anticipating that tiny doses might treat overactive muscles. #### 💬 Quote > Only the dose permits something not to be poisonous. > — Sally Helm Sally Helm on Kerner’s insight and Paracelsus’s principle #### 📚 Transcript **Sally Helm:** 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. **Jean Carruthers:** And when these Germans got sick, their eyelids would droop, their speech would slur. 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. There's a young, newly-minted doctor **Sally Helm:** 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:** 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 these poor people. These people in the German countryside who were struck by this mysterious **Sally Helm:** paralysis. He documents a pattern. All the patients seem to have eaten the same food. They made sausages, **Jean Carruthers:** and the sausages maybe weren't totally clean. You know, maybe there was dirt in the sausages. **Sally Helm:** 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 **Jean Carruthers:** sausages. And so the disease itself, this mysterious paralytic disease, became known as botulism because botulus **Sally Helm:** is Latin for sausage. Okay, so Justinas Kerner, this polymath winemaker poet physician, he describes these symptoms in detail and he does one other surprising thing. He tried it himself. He **Jean Carruthers:** put some of the fatty substance that they had ingested into his own mouth against the advice of his friends. Why did he do that? Oh, because he wanted to know. So his mouth became dry. This was the first instance that anyone had shown that a toxin could stop the activity of your salivary glands. **Sally Helm:** Wow. I mean, it just seems so reckless to do when he knew that it had killed people. What do you make of it? I think that he **Jean Carruthers:** 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 **Sally Helm:** as a potential treatment. It was brilliant. 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 riddle. 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. --- ### [A Biological Weapon Research Program Became Medicine](https://share.snipd.com/snip/bd3524e9-bb5f-435f-a7c9-11255d86c8f4) 🎧 08:08 - 09:12 (01:03) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/4c4daae8-4b4c-4c30-9665-3f63b9e74a92" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Wartime fears about botulinum toxin as a weapon unexpectedly funded research into isolating and controlling it. - Ed Shantz’s purified toxin enabled Alan Scott to treat crossed eyes without surgery. #### 💬 Quote > He is able to isolate the toxin from the bacterial sludge that it grows in. > — Sally Helm Sally Helm on Ed Shantz’s breakthrough #### 📚 Transcript **Sally Helm:** We did figure out some stuff about how to prevent botulism. And then during World War II, the U.S. is worried that Germany and Japan are going to develop botulinum toxin as a biological weapon. So they got a whole bunch of researchers together to study it and look at antidotes. One of them, a guy named Ed Shantz, 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. And he was actually quite **Jean Carruthers:** noble and supplied it to people who were wanting to do research on botulinum toxin. And he sent, I think, **Sally Helm:** 100 milligrams to Alan Scott. 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. --- ### [A Patient Accidentally Discovered Cosmetic Botox](https://share.snipd.com/snip/5c9ebb2b-d0ad-4794-8264-349be8bb6df0) 🎧 09:30 - 10:34 (01:04) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/8e458d30-25db-45dc-ade1-835ab0269489" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Jean Carruthers treated patients whose eyelids spasmed shut, restoring their ability to work and drive. - One patient noticed that injections between her eyebrows created a “beautiful, untroubled expression.” #### 💬 Quote > Every time you treat me there, I [have] this beautiful, untroubled expression. > — Jean Carruthers Jean Carruthers on a patient noticing Botox’s cosmetic effect #### 📚 Transcript **Jean Carruthers:** He **Sally Helm:** is now investigating another use. Maybe botulinum toxin can treat a condition called blepharospasm. These poor people, **Jean Carruthers:** 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 **Sally Helm:** a total game changer. Alan 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. She said, you didn't treat me here, between her eyebrows. **Jean Carruthers:** 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 this beautiful, untroubled expression. --- ### [Jean Carruthers Became Her Own Botox Demonstration](https://share.snipd.com/snip/2f7235ad-45e3-48ba-96eb-6874c0ce771f) 🎧 10:37 - 12:36 (01:59) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/f881594e-0585-4ab8-a70e-e7b692d48c7a" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Jean Carruthers and her dermatologist husband tested botulinum toxin on frown lines after struggling to recruit volunteers. - Their receptionist joined first, and Carruthers injected herself to demonstrate its safety and effect. #### 💬 Quote > I haven't frowned since 1987. > — Jean Carruthers Jean Carruthers on becoming a cosmetic Botox patient #### 📚 Transcript **Jean Carruthers:** Because I happened to have the **Sally Helm:** perfect husband. 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 11s. A lot of people want them gone. But the best treatment at the time doesn't really work. It can 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. Most **Jean Carruthers:** 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 **Sally Helm:** we were over the edge. Crazy. 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:** 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 **Sally Helm:** big deal to her. 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. And I make a joke of it now. I haven't frowned since 1987. **Jean Carruthers:** 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 now. --- ### [Why Botox Became Medicine’s Swiss Army Knife](https://share.snipd.com/snip/82c32664-b451-44cd-9e06-0139ba6a066a) 🎧 14:22 - 16:53 (02:31) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/07b65b06-a4f2-4a5e-b974-a79df3fdd2e3" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Botox spread from ophthalmology to dermatology and then to migraines, sweating, bladder problems, and movement disorders. - Its local action and ability to block nerve signals make it a medical “Swiss army knife.” #### 💬 Quote > If it moves, botulinum toxin can stop it. > — David Simpson David Simpson on Botox’s expanding indications #### 📚 Transcript **Sally Helm:** 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. 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 Beverly Hills. **Axel Wollmer:** 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. We **Sally Helm:** 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 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. **Axel Wollmer:** 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:** 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. --- ### [Choose Botox Injectors With Proper Training](https://share.snipd.com/snip/aec32d8c-70d7-473f-9695-b0a3ce95672b) 🎧 17:04 - 18:15 (01:10) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/1d5939d0-0468-4df5-8632-a6ad5370efd5" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Use trained injectors because localized weakness can spread, causing problems such as drooping eyelids. - David Simpson recommends finding a mentor, since safe treatment requires both science and learned technique. #### 💬 Quote > I usually encourage doctors to find a mentor to train them properly, almost like surgery. > — David Simpson David Simpson on safe Botox practice #### 📚 Transcript **Sally Helm:** Off-label means it's for use that the FDA hasn't officially 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. **Axel Wollmer:** 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. --- ### [Axel Wollmer Tested Botox On His Own Mood](https://share.snipd.com/snip/73b2a384-ff32-4a3d-a919-703b35918f1e) 🎧 18:55 - 20:09 (01:13) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/b7cb30c8-043d-413e-b57c-94e39cc48e99" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Axel Wollmer injected his own frown lines while studying Botox’s possible antidepressant effects. - He described feeling unusually resilient amid the noise and demands of a four-child household. #### 💬 Quote > It was just like a layer of Teflon covering me. > — Axel Wollmer Axel Wollmer on his personal experience with Botox #### 📚 Transcript **Axel Wollmer:** There's an interesting emerging literature on depression. Certainly, I would put that into one of the categories of one of the mystery uses that we don't quite understand. For me, it was really striking how immediately the psychotropic effect occurred. Axel **Sally Helm:** 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 he had a colleague inject him right between the eyebrows on those brown lines. It **Axel Wollmer:** was a little bit painful. The pressure of the fluid in the tissue, it's not a 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 me. It just didn't bother me the way it sometimes does. --- ### [Freezing Frown Muscles Might Affect Depression](https://share.snipd.com/snip/14373ef2-432a-407f-8d87-c9abbd0cb54e) 🎧 20:12 - 22:46 (02:33) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/5f72b932-7306-4b56-b50a-14a1c9fb8b98" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - The facial feedback hypothesis proposes that expressions influence feelings, so preventing frowning might reduce depression. - Early trials were promising, but researchers still need larger studies and do not know the exact mechanism. #### 💬 Quote > If you make frowning impossible, you should feel better. > — Sally Helm Sally Helm on the facial feedback hypothesis #### 📚 Transcript **Axel Wollmer:** Axel **Sally Helm:** 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 this 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 muscles. People build on this idea and come up with something called the facial feedback hypothesis. If **Axel Wollmer:** you're angry, you frown. And this frowning communicates your anger to others. But it also communicates this anger to yourself. And **Sally Helm:** is this a proven idea or it's just... **Axel Wollmer:** Yeah, no, it's a very old hypothesis and it has been proven experimentally. Time it again. **Sally Helm:** That it's not just that I'm happy, I smile. Also, if I smile when I'm not feeling happy, I start feeling happy. Take **Axel Wollmer:** it till you make it. So **Sally Helm:** 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 frowning 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 Wollmer:** There were several independent replications of our findings that uniformly confirmed effect. Axel, **Sally Helm:** 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. --- ### [Botox Research Is Reaching Cancer Treatment](https://share.snipd.com/snip/0a2680f6-5108-427f-9172-2ddef4aed49d) 🎧 22:51 - 24:29 (01:37) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/0ae89067-192e-401b-9d97-5ddf5d4aa5c0" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Botox research continues into wound healing, pain, and cancer by blocking nerve signals that may help tumors grow. - Its journey shows how an extremely dangerous toxin can become useful through precise dosing and unexpected observations. #### 💬 Quote > Some new work suggests that nerves might help tumors grow. > — Sally Helm Sally Helm on emerging cancer research #### 📚 Transcript **Sally Helm:** 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 Wollmer:** So maybe you can inject it into your butt or into your thigh or whatever. You'll be so happy. Yeah. And of course, this is really intriguing. But on the other hand, we don't want to do this study because it leads us too far away from what we know is working. **Sally Helm:** He 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. For **Axel Wollmer:** me, cancer was the most fascinating new indication. I wasn't aware of that. **Sally Helm:** Yeah. Some new work suggests that nerves might help tumors grow. So using Botox to block those signals might help tumors shrink. --- Created with [Snipd](https://www.snipd.com) | Highlight & Take Notes from Podcasts # Snips updated after 2026-09-21T12:05:55 ### [The Doctor Who Tasted Sausage Poison](https://share.snipd.com/snip/7d7f8a56-b7e1-4288-8240-c8b789182a95) 🎧 04:05 - 07:56 (03:51) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/508319cc-f645-4900-8c45-1474b1cc2c08" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Justinus Kerner investigated paralysis linked to contaminated sausages and identified botulism’s effects on salivation and muscles. - He tasted the suspected toxin himself, anticipating that tiny doses might treat overactive muscles. #### 💬 Quote > Only the dose permits something not to be poisonous. > — Sally Helm Sally Helm on Kerner’s insight and Paracelsus’s principle #### 📚 Transcript **Sally Helm:** 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. **Jean Carruthers:** And when these Germans got sick, their eyelids would droop, their speech would slur. 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. There's a young, newly-minted doctor **Sally Helm:** 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:** 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 these poor people. These people in the German countryside who were struck by this mysterious **Sally Helm:** paralysis. He documents a pattern. All the patients seem to have eaten the same food. They made sausages, **Jean Carruthers:** and the sausages maybe weren't totally clean. You know, maybe there was dirt in the sausages. **Sally Helm:** 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 **Jean Carruthers:** sausages. And so the disease itself, this mysterious paralytic disease, became known as botulism because botulus **Sally Helm:** is Latin for sausage. Okay, so Justinas Kerner, this polymath winemaker poet physician, he describes these symptoms in detail and he does one other surprising thing. He tried it himself. He **Jean Carruthers:** put some of the fatty substance that they had ingested into his own mouth against the advice of his friends. Why did he do that? Oh, because he wanted to know. So his mouth became dry. This was the first instance that anyone had shown that a toxin could stop the activity of your salivary glands. **Sally Helm:** Wow. I mean, it just seems so reckless to do when he knew that it had killed people. What do you make of it? I think that he **Jean Carruthers:** 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 **Sally Helm:** as a potential treatment. It was brilliant. 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 riddle. 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. --- ### [A Biological Weapon Research Program Became Medicine](https://share.snipd.com/snip/bd3524e9-bb5f-435f-a7c9-11255d86c8f4) 🎧 08:08 - 09:12 (01:03) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/4c4daae8-4b4c-4c30-9665-3f63b9e74a92" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Wartime fears about botulinum toxin as a weapon unexpectedly funded research into isolating and controlling it. - Ed Shantz’s purified toxin enabled Alan Scott to treat crossed eyes without surgery. #### 💬 Quote > He is able to isolate the toxin from the bacterial sludge that it grows in. > — Sally Helm Sally Helm on Ed Shantz’s breakthrough #### 📚 Transcript **Sally Helm:** We did figure out some stuff about how to prevent botulism. And then during World War II, the U.S. is worried that Germany and Japan are going to develop botulinum toxin as a biological weapon. So they got a whole bunch of researchers together to study it and look at antidotes. One of them, a guy named Ed Shantz, 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. And he was actually quite **Jean Carruthers:** noble and supplied it to people who were wanting to do research on botulinum toxin. And he sent, I think, **Sally Helm:** 100 milligrams to Alan Scott. 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. --- ### [A Patient Accidentally Discovered Cosmetic Botox](https://share.snipd.com/snip/5c9ebb2b-d0ad-4794-8264-349be8bb6df0) 🎧 09:30 - 10:34 (01:04) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/8e458d30-25db-45dc-ade1-835ab0269489" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Jean Carruthers treated patients whose eyelids spasmed shut, restoring their ability to work and drive. - One patient noticed that injections between her eyebrows created a “beautiful, untroubled expression.” #### 💬 Quote > Every time you treat me there, I [have] this beautiful, untroubled expression. > — Jean Carruthers Jean Carruthers on a patient noticing Botox’s cosmetic effect #### 📚 Transcript **Jean Carruthers:** He **Sally Helm:** is now investigating another use. Maybe botulinum toxin can treat a condition called blepharospasm. These poor people, **Jean Carruthers:** 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 **Sally Helm:** a total game changer. Alan 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. She said, you didn't treat me here, between her eyebrows. **Jean Carruthers:** 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 this beautiful, untroubled expression. --- ### [Jean Carruthers Became Her Own Botox Demonstration](https://share.snipd.com/snip/2f7235ad-45e3-48ba-96eb-6874c0ce771f) 🎧 10:37 - 12:36 (01:59) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/f881594e-0585-4ab8-a70e-e7b692d48c7a" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Jean Carruthers and her dermatologist husband tested botulinum toxin on frown lines after struggling to recruit volunteers. - Their receptionist joined first, and Carruthers injected herself to demonstrate its safety and effect. #### 💬 Quote > I haven't frowned since 1987. > — Jean Carruthers Jean Carruthers on becoming a cosmetic Botox patient #### 📚 Transcript **Jean Carruthers:** Because I happened to have the **Sally Helm:** perfect husband. 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 11s. A lot of people want them gone. But the best treatment at the time doesn't really work. It can 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. Most **Jean Carruthers:** 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 **Sally Helm:** we were over the edge. Crazy. 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:** 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 **Sally Helm:** big deal to her. 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. And I make a joke of it now. I haven't frowned since 1987. **Jean Carruthers:** 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 now. --- ### [Why Botox Became Medicine’s Swiss Army Knife](https://share.snipd.com/snip/82c32664-b451-44cd-9e06-0139ba6a066a) 🎧 14:22 - 16:53 (02:31) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/07b65b06-a4f2-4a5e-b974-a79df3fdd2e3" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Botox spread from ophthalmology to dermatology and then to migraines, sweating, bladder problems, and movement disorders. - Its local action and ability to block nerve signals make it a medical “Swiss army knife.” #### 💬 Quote > If it moves, botulinum toxin can stop it. > — David Simpson David Simpson on Botox’s expanding indications #### 📚 Transcript **Sally Helm:** 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. 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 Beverly Hills. **Axel Wollmer:** 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. We **Sally Helm:** 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 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. **Axel Wollmer:** 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:** 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. --- ### [Choose Botox Injectors With Proper Training](https://share.snipd.com/snip/aec32d8c-70d7-473f-9695-b0a3ce95672b) 🎧 17:04 - 18:15 (01:10) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/1d5939d0-0468-4df5-8632-a6ad5370efd5" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Use trained injectors because localized weakness can spread, causing problems such as drooping eyelids. - David Simpson recommends finding a mentor, since safe treatment requires both science and learned technique. #### 💬 Quote > I usually encourage doctors to find a mentor to train them properly, almost like surgery. > — David Simpson David Simpson on safe Botox practice #### 📚 Transcript **Sally Helm:** Off-label means it's for use that the FDA hasn't officially 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. **Axel Wollmer:** 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. --- ### [Axel Wollmer Tested Botox On His Own Mood](https://share.snipd.com/snip/73b2a384-ff32-4a3d-a919-703b35918f1e) 🎧 18:55 - 20:09 (01:13) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/b7cb30c8-043d-413e-b57c-94e39cc48e99" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Axel Wollmer injected his own frown lines while studying Botox’s possible antidepressant effects. - He described feeling unusually resilient amid the noise and demands of a four-child household. #### 💬 Quote > It was just like a layer of Teflon covering me. > — Axel Wollmer Axel Wollmer on his personal experience with Botox #### 📚 Transcript **Axel Wollmer:** There's an interesting emerging literature on depression. Certainly, I would put that into one of the categories of one of the mystery uses that we don't quite understand. For me, it was really striking how immediately the psychotropic effect occurred. Axel **Sally Helm:** 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 he had a colleague inject him right between the eyebrows on those brown lines. It **Axel Wollmer:** was a little bit painful. The pressure of the fluid in the tissue, it's not a 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 me. It just didn't bother me the way it sometimes does. --- ### [Freezing Frown Muscles Might Affect Depression](https://share.snipd.com/snip/14373ef2-432a-407f-8d87-c9abbd0cb54e) 🎧 20:12 - 22:46 (02:33) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/5f72b932-7306-4b56-b50a-14a1c9fb8b98" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - The facial feedback hypothesis proposes that expressions influence feelings, so preventing frowning might reduce depression. - Early trials were promising, but researchers still need larger studies and do not know the exact mechanism. #### 💬 Quote > If you make frowning impossible, you should feel better. > — Sally Helm Sally Helm on the facial feedback hypothesis #### 📚 Transcript **Axel Wollmer:** Axel **Sally Helm:** 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 this 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 muscles. People build on this idea and come up with something called the facial feedback hypothesis. If **Axel Wollmer:** you're angry, you frown. And this frowning communicates your anger to others. But it also communicates this anger to yourself. And **Sally Helm:** is this a proven idea or it's just... **Axel Wollmer:** Yeah, no, it's a very old hypothesis and it has been proven experimentally. Time it again. **Sally Helm:** That it's not just that I'm happy, I smile. Also, if I smile when I'm not feeling happy, I start feeling happy. Take **Axel Wollmer:** it till you make it. So **Sally Helm:** 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 frowning 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 Wollmer:** There were several independent replications of our findings that uniformly confirmed effect. Axel, **Sally Helm:** 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. --- ### [Botox Research Is Reaching Cancer Treatment](https://share.snipd.com/snip/0a2680f6-5108-427f-9172-2ddef4aed49d) 🎧 22:51 - 24:29 (01:37) <iframe src="https://share.snipd.com/embed/obsidian-player/snip/0ae89067-192e-401b-9d97-5ddf5d4aa5c0" width="100%" height="100" style="border: none; border-radius: 12px;" sandbox="allow-scripts allow-same-origin allow-forms allow-popups allow-clipboard-write" ></iframe> - Botox research continues into wound healing, pain, and cancer by blocking nerve signals that may help tumors grow. - Its journey shows how an extremely dangerous toxin can become useful through precise dosing and unexpected observations. #### 💬 Quote > Some new work suggests that nerves might help tumors grow. > — Sally Helm Sally Helm on emerging cancer research #### 📚 Transcript **Sally Helm:** 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 Wollmer:** So maybe you can inject it into your butt or into your thigh or whatever. You'll be so happy. Yeah. And of course, this is really intriguing. But on the other hand, we don't want to do this study because it leads us too far away from what we know is working. **Sally Helm:** He 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. For **Axel Wollmer:** me, cancer was the most fascinating new indication. I wasn't aware of that. **Sally Helm:** Yeah. Some new work suggests that nerves might help tumors grow. So using Botox to block those signals might help tumors shrink. ---