The accidental rise of Botox

The semester-by-tag lab-tabücher soft-behind the internet.

It's a master's real-time.

“I'm saying, you can say that you're a jerk.”

You're a master, right? But you don't understand. Egal, it's a failure for a job. Do you just do it with this story? And if you then work, you'll be able to do it.

- That's right? - Safe. This story is... - You're right. - Now you're a lawyer. In the entire European Union. For reference, like football, for young kids?

I don't know. 10,000 electrophacs, and it's worth ever more. Based on the plans for our free partner in the EU and Great Britain, within the 26th century. It's unexplainable.

I'm Sally Helm.

And a couple of months ago, I was up very early.

Walking down the street in Manhattan. I'm my lawyer. There's someone on a five-am run. Wow. 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 injected 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 got in 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 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 Carrothers. She knows the story because Botox will become very important in her career. 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 living nearby,

just dinosaur, and he is called in to investigate. Just dinosaur 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. 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, just dinosaur, he did his medical thesis on 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. They made sausages. And this sausages maybe weren't totally clean.

You know, maybe there was dirt in the sausages. 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 so the disease itself, this mysterious paralytic disease became known as bachelorsum. Because bachelors is Latin for sausage. OK, so just dinosaur. This polymath wine maker poet physician.

He describes these symptoms in detail. And he does one other surprising thing. He tried it himself. He put some of the fatty substance that they had ingested into his own mouth,

against the advice of his friends. What? And 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 salary cleanse. 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 just had a little taste.”

I think it 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 overact the muscle conditions. He saw the other side of the poisoning as a potential treatment. It was brilliant.

I have an instinct here to be like,

"That is poison just dinosaur, 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.

Paracelsis, 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.”

Counter-earth 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 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 Chance, is able to isolate the toxin from the bacterial sludge that it grows in.

After the war, he makes a whole batch of it and his lab in Wisconsin. 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, a hundred milligrams to Ellen Scott.”

Alan Scott is an ophthalmologist. And he has this idea that botulinum toxin could help cure extremists. 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 Carrathers enters the story. I was a pediatric hospitalologist at the University of British Columbia in Vancouver.

And I started reading about it and got really fascinating. So she gets herself a fellowship with Alan Scott. He's now investigating another use. Maybe botulinum toxin can treat the condition called blepharospasm.

These poor people, they can't count on their eyes opening. Their eyes spasm shot. 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.

Alan teaches Dean 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. And I apologize 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, untrubbled expression. Now, this is when the penny dropped.

Because I have the perfect husband. Jean's perfect husband, Alistair, is a dermatologist. And Jean's heard him complain about how difficult it is to treat those frown lines between the eyebrows. The elevenths.

A lot of people want them gone. But the best treatment at the time doesn't really work. He can even be dangerous.

She tells Alistair that she has this idea.

“Botulinum toxin could solve that problem.”

He frees 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.

That is not happening. Most people in the world were running a mile from it. They would know 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. 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. She is at there for four years.

Watching online 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 for her. And then Jean pulls a justine as corner. 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.

“But that's how I got 18 patients into our study.”

They would say, no, I'd suppose. And I would say, well, what do you think? And I'd show them my brown line picture from before. And my brown 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 of it.

Mark Twaim said wrinkles should merely indicate where smiles have been. He didn't know about Botox. Alan Scott had sold his initial patent to a farm company called Allergan, that mostly did eye care. The co-authors that sell them a patent to Botox, by the way,

is actually just one of the brand names for Botulinum toxin. It's like how we call all tissues clean acts. Now, Gene also makes money on this, including by doing research and consulting for the farm economy. And the old sausage poison goes totally mainstream.

It has a whole life that just minus kernor could never have foreseen.

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 shifted around the world. The stuff is still poisonous at large doses. Don't want that playing getting hijacked.

And things can very occasionally go wrong with cosmetic Botox, especially if you get it from a bad injector. But for Gene, obviously it's been a good thing. I mean, she doesn't frown since 1987. I've seen you called the godmother of Botox.

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

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. Oh, are they sweet? I apologize, Nia. Oh, that's not as if you ingest your lethal amount. If I have a patient that comes in, they're 18 years old.

They don't have any lines.

“I mean, why don't you wait a couple of 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 all of the conditions that Botox is used to treat? That would take probably much longer than we have time to do.

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. 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.

David himself first uses this toxin back in the early 90s,

so just a little while after Jean makes her wringled discovery. He is treating a patient with a traumatic brain injury who has what is called spasticity in one of his arms.

The elbow was flexed.

It was crunched up like a pretzel.

And he developed a large calcium deposit in the inner elbow. He needed surgery to fix this, but his surgeon couldn't get the arm to relax. So he goes to David. And he 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 if it'd done at that time. And so we got approval from the medical board for use. We injected it into this patient, and he responded nicely in the arm opened up. 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 hyperhydrosis or excessive sweating. They try it on overactive bladder. We have to peel it 50 times a day.

It helps those patients do. And meanwhile, the cosmetic use is picking up steam. And there's a plastic surgeon on Beverly Hills. Who was injecting individuals for their wrinkles, cosmeticly. And the individuals who was treating for wrinkles came back and said,

"You know, my migraines are less." Then that led to studies in my grain.

That ultimately received an FDA approval on widely used today.

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 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. One of the adages I often use to describe the indications is if it moves, butulinum toxin can stop it. And actually, we now extend that to if it hurts,

then butulinum toxin may help relieve the pain as well, because that's an emerging area of use.

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 effects 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 very used 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.

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 butchillum 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. 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. And 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, 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.

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

Axel Volmer 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 on those brown lines. It was a little bit painful. It's the pressure of 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 peflon covering. It just didn't bother me the way it sometimes does. And inject kind of resilience.

“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. And 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 brown lines. He calls them the grief muscles. People build on this idea and come up with something called the facial feedback hypothesis. If you're angry, you're frown.

And this frowning communicates your anger to others. But it also communicates this anger to yourself. And is this a proven idea? Or it's just... Yeah, it's a very old hypothesis.

And it has been proven so it is experimentally. Time to get 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. I could do you make it. So 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 look 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 the botox could work as an antidepressant. Then other researchers got in on this. There were several independent replications of all findings that uniformly confirm this effect.

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

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

He said first, they wanted 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 they're excessive sweating or their migraines really improved. This toxin has a lot of uses and we are still finding more.

Botulinum toxin and paint.

“For me, the cancer was the most fascinating new indication that wasn't the well of that.”

Yeah, some new works suggest that nerves might help tumors grow. So using Botox to block those signals might help tumors shrink. Botox to treat cancer. Not about journey for one of the deadliest poisons known to man.

“This episode was produced by me, Valley Home.”

It was edited by Joanna Solitarov with help from Julia Longoria, mixing and sound design from Christian Ayala, fact checking from Melissa Hirsch and Sarah Schweppi. Special thanks today to Ed Chapman, Eric Finsey and Peter McCollister. Meredith Hadnott runs the show.

“Jorge Just is our editorial director, Amy Padula and Nome Hassanfeld are not experimenting on themselves unlike many people in this story.”

And Bird Pinkerton kept thinking about what the doctor best 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 Resnick for co-creating the show along with Bird and Nome.

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