Daniel and Kelly’s Extraordinary Universe - Going under: The history and mechanisms of general anesthesia

Episode Date: July 17, 2025

Daniel and Kelly explore the history of general anesthesia, and what we know (or don't know) about how it works.See omnystudio.com/listener for privacy information.

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Just a heads up that on today's episode, we're going to be talking about the history of anesthesia. We'll also be discussing medical procedures in the pre-anesthesia era. And we'll touch on triggering topics like mental health crises and suicides. Since one of my best friends is a physicist who likes to get philosophical from time to time, I sometimes find myself in discussions about time travel, which inevitably bring up the question of when in space and time I'd like to be alive if it were up to me. It would be amazing to see early human species create complex tools or communicate complicated ideas to each other for the first time, or sit at a table with Antoine von Leyenhook

and ask him how to pronounce his name correctly while looking through his microscope to see microscopic creatures swimming around in a drop of water, or to sit in the hall at the Royal Society when Charles Darwin and Alfred Russell Wallace's theory of natural selection is shared publicly for the first time. Any of those moments would be amazing to witness firsthand, but my answer is way more practical. I want to be alive in a time and place that has good sanitation, antibiotics, and critically, anesthesia. Dr. Lindsay Fitzherris is a medical historian and author, and the prologue to her book, The Butchering Art, makes it incredibly clear why living in the age of anesthesia is super awesome. Here, I'm going to recall a story from the beginning of her book.

It was December 21st, 1846, and the crowd of medical professionals and spectators were settling in to the operating theater at London's University College Hospital. In the middle of the room was a blood-soaked table. The floor was covered in sawdust to soak up the anticipated forthcoming pools of blood. Surgery on that day would be performed by the famous Dr. Robert Liston, who was well-known for completing surgeries in 30 seconds or less. And we know that it took 30 seconds or less because he often started his surgeries by proclaiming, Time me, gentlemen, time me.

Now, if you have a limb that needs to be amputated, you can be forgiven for wanting to get it done by the guy who does it in under a minute. But speed sometimes came at the cost of accuracy, as Liston once coupled a leg amputation with an accidental testicle ectomy. Most people avoided surgeries at all costs. Not only was it an absolutely miserable experience

to be held down by surgeon assistance while you were cut into, but if that experience didn't kill you, subsequent infection often did, as this was in the era before sterile technique and antibiotics. And it was gruesome to watch, too. Physician James Simpson once fled an operating theater because it was too much for him to watch a breast removal surgery. After escaping the theater, he proclaimed that he would instead study law. He did, however, go on to complete his medical training, and we'll hear more about his pioneering work on anesthetics for childbirth later in the episode. But anyway, on this day, in front of a crowded theater, Liston was trying the anesthetic ether for the first time.

A 36-year-old butcher who needed a leg amputation was laying on the bench, and the ether was administered, knocking them out. The leg was quickly sought off, the arteries tied off, and the flesh closed up. All this was completed in just a few minutes. When the groggy patient came to, he looked at Liston and asked, when would the surgery begin? Amazing. Welcome to Daniel and Kelly's Extraordinary Universe. Hi, I'm Daniel. I'm a particle physicist, and my most terrifying experience with anesthesia was having my 10-year-old son go under. Oh, hi, I'm Kelly Wienersmith. I study space and parasites, and thus far, none of my kids, have had to go under anesthesia. I've had anesthesia make me vomit and embarrass myself many times,

but I've never been scared about it. What was so scary about your kid going under? The fact that nobody knows what they're doing or how it works, and they're like, there's a pretty good chance he'll wake up. And we're like, what? But Daniel, it's more than just a pretty good chance. Like, we've got a lot of experience with this by now. Yeah, we have played a restroom with this many, many times, and mostly people survive. And that all is fine scientifically, but when it's your kid going under, it's an emotional decision and probabilities and statistics are irrelevant. Yeah. It's just terrifying.

Yep. Have you ever said anything particularly stupid coming out of anesthesia? That assumes I don't say stupid things when I'm not under anesthesia. So I think my distribution of intelligence and stupid doesn't change. How about you? Have you said absurd stuff coming out of anesthesia? I don't remember. But Zach told me that after I came out of a procedure, I just kept asking, was I polite to everyone?

Was I polite to everyone? And I just kept asking, I was really panicking about whether or not I was polite to everyone. And Zach said I was fine. And then I threw up. But I didn't feel the procedure, which is great. Well, I'm sure you're always polite, really when you're in pain or when you're out of it. Thanks. Yeah.

Apparently, I really worry about that. And I'm sure that today you're going to give us a. a very painless tour of the history of anesthesia, what we know about it, how we've discovered it, and how many humans have suffered unnecessarily through history. Yes, well, I am attempting today to politely answer a wonderful question from our listener, Eric, and let's go ahead and hear that question now. Hey, there's a whole lot of important stuff that we don't fully understand,

tangents, as part of the plane episode, was my favorite part. I think I remember reading once that we don't really know how anesthesia works. Is that true? Seems like a cool episode idea. History of anesthesia, back when getting someone really drunk was the best we could do, to what we do now and if we actually understand it, to the differences between anesthesia and sleep. Thanks. Oh my gosh, there are so many cool topics in that question. I got to go down so many amazing rabbit holes. And if you would like to submit a question about whatever it is that keeps you up at night, please send us those questions at questions at Daniel and Kelly.org. This question makes me wonder how much we do and don't know about why things work in medicine. I actually asked Katrina about this when I read this question, and she was like, you should be less surprised. We don't know how Tylenol works.

I was like, I'm less surprised now, but I'm more terrified, I guess. That like basically our bodies are huge Rube Goldberg machines and we don't know how they work. But we have discovered if you press this button and pull this lever that this thing happens. and now we rely on that for all of modern medicine. I think my scariest example of this, and I think I've said this on the show before, so I'll keep it brief, is I was talking to someone about why deep brain stimulation works

where you essentially like stick an electrode in the center of someone's brains and shock it, which is usually to stop a seizure. And they were like, we don't know. I was like, wow, we're shocking the insides of people's brains and we're like, it works and that's great, but why? I know. I know. And the physicist, to me, wants to be like really reductionist,

be like, we have to understand how these things work if we're going to do them, right? Like, because who knows what other consequences there could be? And also it makes me wonder, like, how do we figure this stuff out? If we don't know how it works or what it was going to do, have we basically just been experimenting on ourselves, unethically on other people for millennia? Like, this is terrible. On the other hand, like, you know, you've got to make progress. It's going to be a long time before we have an understanding of the human body that would

satisfy a physicist. And we have kids who need anesthesia. when they go under. So yeah. Yeah. Well, and so that's actually a really nice transition into a book that I used to do a bunch of the research for this episode. It's Dr. Lawrence Altman's book, Who Goes First? And it's essentially trying to figure out who should we test this stuff out on first to make sure that it's safe. And this book is all about self-expermentation and medicine, basically doctors who decided, I am the right person to test it on first because I understand the risks

and I'm the one who has the idea. And so they tested it on themselves. And there's a lot of self-expermentation in the history of anesthesia. Is that sort of on the down low? I know that you're not allowed to experiment on people unless you have all sorts of ethical reviews, et cetera. But are there such reviews for experimenting on yourself? Can you basically do anything you want to your own body? Where should I start here?

So I got kind of interested in this question. And after World War II, and I promise I won't do like nearly 100 years of history on this question, but after World War II, there was the Nuremberg Code. And this was in response to the horrible experiments that not see doctors did on people in their concentration camps, and one of the things that they were encouraging was, like, if you're going to do a procedure on someone, you need to be willing or actually you need to do it on yourself. Because that is a way to show that, like, you think this is safe, you're invested, blah, blah, blah. And so for a while there, it was encouraged for people

to do it on themselves. Now you're not supposed to experiment on yourself unless you were included in the permits and protocols that you submitted to get permission. And so you can say, I need 100 subjects, and the first one is going to be me. But, yeah, you're not supposed to just willy-nilly experiment on yourself, though. I have heard of people who do that anyway. And I wonder if once you do that, if you break the rules, if that data is not allowed to be considered in future questions, you know, sort of like Dr. Mengele's data. Or if they're like, well, you have this data, you did it already. So let's use it.

You know, I've also come across a lot of examples where people have experimented on themselves. They got the answer they expected. And then they moved forward as though they knew what they needed to know. But it's turned out their sample size of one was completely misleading. And I've seen this in like trials for vaccines. Not anymore. These kinds of data would not fly anymore just to be clear. But in the past, people have like tried a vaccine on themselves, been like,

this worked great on me and then distributed it widely and turned out it works very different in different kinds of bodies. So you can learn something from a sample size of one. But then you need to follow it up with much better, much more broad. So let's zoom in and talk about today's topic, which is not how the whole human body works, but how we put parts of it to sleep. Yeah. Let's go all the way back to very early history. Like, what were people doing thousands of years ago when they needed to have surgery?

So I don't know many thousands of years ago, but something like one to two thousand years ago, we were just trying stuff out, which is maybe not so different than what we do now, but we've got better evidence now. But so there's evidence of Chinese and Arab physicians inhaling various kinds of drugs, mixing things in alcohol, and this apparently helped with surgery. But we've sort of lost the recipes. The physicians were doing drugs and that helped them with the surgery or the patients were getting the drugs. If I needed to amputate someone's limb, maybe I would want to be not completely present for that process. Like, past the pipe there, dude, when you're done with it. That's right. That's right.

But so we don't really have great data on what it was that they were doing, but we do have some fun stories from like French surgeons from a long time ago who would knock people out, not with drugs, but by putting a wooden bowl over someone's head and hitting it with a hammer to like literally knock you out. Oh, my gosh. And then for a while attempting to mesmerize patients, you know, like hypnotizing them was popular. But then it became clear that some people were saying this worked and they were actually just like tricking a bunch of people. So that fell out of favor. But then what is kind of frustrating is that around 1799, it was discovered that actually nitrous oxide does make it so that you don't feel pain. So Humphrey Davy, was he a physics guy? I don't know. I never heard of him. Oh, gosh.

I heard his name before, and I just assumed he was a physicist. Why did you assume he was a physicist? Because people don't care about old biologists. He sounds to me like a guy who would sit on a wall and then fall off and crack. Yep, yep. Oh, he's a chemist. Oh, God. All right. Yeah, knock him off that wall. That's right. That's right. So in 1799, Humphrey Davy had a job where he was experimenting on various things. And one of the things he was experimenting with was nitrous oxide, which is also called laughing gas.

And he was experimenting with his friends who included the poet Samuel Taylor Coolridge and Dr. Peter Rodget, who was the guy who compiled the the thesaurus. But anyway, they were sort of like knocking themselves out with nitrous oxide. And Humphrey Davy mentioned, oh, hey, when I take this, my headaches go away and my wisdom teeth don't hurt anymore. And so he noted it could be used for surgeries to remove pain. But then he goes on and does other stuff, like he gets knighted for inventing the minor safety lamp. And he never pursues this line of reasoning. So from as early as 1799, we could have been using things like nitrous oxide to knock people out in surgeries. but this just sort of like disappeared into the ether

and was an idea that didn't get followed up on. Chemists, oh my gosh, what are you doing? Keeping secrets of painless surgery from the masses. Well, I mean, no, he shared this result, like, in a report, but then he moved on to other things. But, you know, let's both agree that chemists could be doing better. So before 1799, before the discovery of nitrous oxide, people would just, like, grin and bear it.

You know, they would, like, drink whiskey or smoke cannabis or pull from the opium pipe, it must have meant that a lot of people avoided necessary surgeries because they were just like, yeah, it's just not worth it. Yeah, so literally you would be, you know, we'd take a couple shots of some alcohol.

A team of big dudes would be brought in to hold you down. And then the surgeon would try to do things as fast as they could. And so surgeons were often picked, not for their skill, but for their ability to saw through things really super fast. Lindsay Fitzherris has this great book called The Butchering Art

that included a bunch of stories of really horrible things like a surgeon who was trying to cut through a leg and did it really fast and also took half of a scrotum with the leg. Bonus. Yeah, I guess. Not for the guy who was under the knife. But yeah, so there were a lot of surgeries

that they wouldn't do. Like maybe they had an inkling that surgery would help in this case. But it was a procedure that just would have been too hard to hold someone down for. They might have lost too much blood. And so only the things that could be done fast were done and they were done by people who were moving quickly, perhaps at the expense of moving carefully. Right. Maybe it's more of a last-ditch option.

Oh, God, yeah. Well, but as a research nerd, I'm curious, how do we know these things about the earliest surgeries? Like, do we have written records from China or, you know, the Islamic world or what is the sort of earliest record we have of medicine and surgery? So the earliest record that I came across while doing the research was 200C.E where a Chinese physician was mixing alcohol with some other stuff. But the references that I read never included. And we learned this from an ancient scroll that was found in such and such tomb or something like that. So I don't know the history of how this information came to be known. But I do know that more recently, for example, some of the stuff I'm going to be talking about next was like in the news and in letters written from one physician. to another, but this was all much more recent. Fascinating. I wonder what they did in ancient Egypt, for example.

You know, those guys are pretty advanced, especially in surgery, right? They, like, took organs out and put them in weird vessels and stuff, so they knew their way around a body. Does it count as surgery if they're dead, though? Like, I mean, it didn't. I think they were also unimpressed with the brain, for example, and thought that, like, the heart is where most of the important stuff happened. So I don't know that I'd want an ancient Egyptian surgeon to be working on me. All right, so let's fast forward back to the president. You said Humphrey Davy missed his opportunity to save people from pain

and just enjoyed hanging out with his friends, Sam Coleridge and Peter Rajit. What happened next? When did we actually start to figure stuff out and use it to save people from suffering? Well, before we were saving people from suffering, we were allowing people to have a really stinking good time. And so in the early to mid-1800s, there were events called Etherfrollics or Jags, where essentially people would get together huff ether and appreciate how awesome it made you feel. And there was no like sort of surgical implication or plans to like understand how this would work in surgery.

It was just like, whoa, it's really fun when you huff ether or huff nitrous oxide. And let's have a biology physics disentanglement moment here because in physics, ether refers to this concept that space is filled with something for light to propagate through famously disproven by the Michelson-Morley experiment. late 1800s. That's not where people are snuffing at your biology parties, right? No. A chemist would tell you that ether is an organic compound. It's a mix of oxygen with alcohol groups, and we both know that I don't know much about chemistry. But no, it's not a made-up idea. It is an actual chemical compound. And what happens when you sniff it? You just like feel good or you pass out or what happens? Well, we'll go into more detail about what it's doing to the brain a little bit later. But for the purpose of these parties, it just sort of made you feel kind of silly and anything that hurt stopped hurting. And you'd laugh a lot more. And, you know, that all sounds fantastic. That sounds great. Why did it go out of fashion? Well, because it's also kind of dangerous. It can lead to vomiting and death. And if you do it too often, it can, like, impact your organs and it's, yeah, bad news. And we will encounter stories about some people who are thought to have maybe gone a little bit mad on account of all the ether and stuff they were taken. Probably chemists.

Yeah, I know, right? Almost certainly chemists. God, guys. All right. So let's take a break here. And when we get back from the break, we'll talk about the four men who brought anesthetics to the medical world and their downfall afterwards as they all fought for credit for being the first to come up with this idea. Oh, no. to Pretty Private with Ebeney, the podcast where silence is broken and stories are set free. I'm Ebeney, and every Tuesday I'll be sharing all new anonymous stories that would challenge your perceptions and give you new insight on the people around you. On Pretty Private, we'll explore the untold experiences of women of color who faced it all, childhood trauma, addiction, abuse, incarceration, grief, mental health struggles, and more. and found the stream to make it to the other side.

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We were talking about ether parties, which do sound fun, but I would not engage in an ether party because I'm a wimp. And you're so wholesome, Kelly. Yeah, I worked in this lab once where somebody said something to me to the effect of, you're really nice. And it was like in a condescending, I've never had anyone be like, you're nice and that kind of sucks. But like, anyway, so I have been told that I'm not fun. But that's fine. I'm not fun.

You're a lot of fun. But wait, let me ask you a more personal question, which is, what is your drug of choice? Are you an alcohol drinker? Do you chew on banana peels? How does Kelly unwind? Kelly does not enjoy chewing on banana peels at all. It makes Kelly feel really uncomfortable. Kelly enjoys a glass of red wine and caffeine. Kelly mostly lives a stimulant-free life. You know what, Kelly's favorite stimulant is the anti-anxiety medication she's on. That's how I roll. That's the modern day ether. What about you?

I'm a big believer in caffeine. as well, and I enjoy red wine. And for many years, I did also enjoy banana peels. It helped stimulate some creativity in my research, but no longer. Ah. Well, we all have had youthful indiscretions. All right. So now let's talk about the indiscretions of various men in history who brought us anesthesia.

So the first person we're going to chat about is Dr. Crawford Long, and he was at one of these ether frolics, and he was really enjoying it. And he noted to himself that when he or others did things that should be painful, they didn't seem to feel the pain. And he was a physician. And this made him think, oh, you know, maybe this could be used in surgery. And so he was the first person to actually test it out. So he had a patient who needed two small cysts removed. And the patient was nervous about getting the surgery done because it was painful.

And he was like, look, this isn't critical. I don't want these things taken out. And the patient had also tried ether recreationally and really enjoyed it. And so Long was like, look, let's try it. I'm going to put you under the ether. You know that you don't feel as much pain under the ether. So let's see how it goes. And actually, it went great.

Wow. And Long started using this gas for other operations as well. But the big thing here is that he didn't share this information with the medical profession widely. So he didn't, like, write a paper or go to a surgery that was watched by a lot of other people. So at the time, surgeries were done in operating theaters where students of medicine, of medicine, we're sort of sitting in the same room. So now, like, you know, if you've watched Gray's Anatomy, you know that there's like an elevated area and you can be behind glass and you can sort of peek in.

Like a splash guard there and make sure you don't get sprayed in the face. I'm wondering if maybe they're protecting the patient more than anything. Like you're, you know, when you sneeze, they don't want the germs settling into the patient's abdomen. But I wonder if they used to pass around raincoats the way they do like SeaWorld in the first few rows, you know? Oh, so gross. I know they used to put sawdust under the operating tables to absorb.

the blood. Yeah, intense. And I don't think they always cleared the sawdust before the next person. And I read some stories where the guy would like take the saw where he had amputated a leg and he'd kind of like wipe it off on his apron and then get to the next guy, which we don't do anymore. And who would come to these things anyway? Is it just medical students or is this like, you know, an afternoon with the family? What are we going to do? This is before movies.

Let's go see some legs get cut off. I don't know if you bring little Susie with you, but like definitely the medical students. are there, and this isn't too far after people used to go to, like, public executions for funzies. Yeah, that's what I was thinking. Yeah, and so I do think some people did come off the streets just to kind of watch. That's probably not how I'd spend my day. When was Shakespeare around? Like, were the options to go to the globe and see a Shakespearean play or watch someone get their leg amputated? My timeline of history. Not a hard choice. I mean, geez. Shakespeare's a couple hundred years before, he's like early 1600s, late 1500s. Oh, all right. Well, then maybe I would watch

the amputation, you know? What else are you going to do in London? So anyway, Long gets the ball rolling but doesn't share with anyone, so it stops with him. But then in 1844, a dentist called Horace Wells goes to a nitrous oxide demonstration. So there were people who would travel around the country and they would essentially get up on a stage and they'd be like, this nitrous oxide stuff is great. Is there a volunteer from the audience who would like to feel, you know, what nitrous oxide feels like. So they'd have them inhale some nitrous oxide and then they'd be like, I feel

great, he-h-h-h-h-h-h-h-h-h. And people would watch this. And they're like, let's amputate your leg. Sure, he-h-h-h-h-h-h-h-h-l. And so Wells was watching this demonstration and one of the people who got sort of exposed to nitrous oxide got a pretty big laceration on their leg but clearly

didn't feel it while it was happening. And so Wells afterwards goes to the guy doing the demonstration and is like, Hey, I saw that someone got hurt and then they were totally fine. Wow. And I'm a dentist. So can you, like, come with me to my dentist office and we can try, like, knocking out my patients before doing the procedure? This is a dentist who cares, who doesn't want to cause his patient's pain.

That's right. Amazing. I miss. Oh, you, this is a joke about dentists in general. I didn't get it because I have an amazing dentist. I love him so much. I hope he listens to the pod and hears how much you love him. You're the best, Dr. Katyn.

Okay, so before he started using it on his patients, he decided he wanted to try it on himself. So this is an example of self-experimentation. So Wells calls over a dentist friend of his. The guy who did the nitrous oxide demonstration knocks Wells out. And the friend dentist who came over pulled out a molar, and Wells doesn't feel a thing. So he just, like, sacrifices a healthy molar to science. Yes. Yeah, he does.

I like this dentist. Yeah, no, me too. He's willing to, like, get his hands dirty for the arts. I appreciate that. All right. So far, I'm voting for Horace Wells to get credit for this. I like Wells, too. So Wells does this on 15 other patients, and he decides this is awesome, right? Yeah. So in 1845, he goes to Massachusetts General Hospital, and they're doing one of these big public surgeries. And he decides he's going to remove a tooth from a volunteer, but he doesn't give the volunteer enough nitrous oxide. Oh, no.

And so now we know that, you know, some people require. more nitrous oxide to get knocked out. Some require less. And this guy just didn't get the right amount for whatever reason. And so the patient is clearly feeling pain during this procedure. And it is very embarrassing to Dr. Wells because he's got this whole audience and it's clearly not working. And so this was sort of devastating for him. This is his big moment. Wow. This was his big moment. And we'll see that he doesn't actually emotionally recover from this. Oh, no. I know. I know. He needs some like emotional nitrous oxide. He needs some of that antidepressant. He does need some antidepressants, as we'll seem. So then the next group that gets in on this at around the same time is Dr. William Morton and his chemistry teacher, Dr. Charles Jackson. Morton starts experimenting with ether instead of nitrous oxide. And it turns out that ether sort of works a little bit better. And at the time, the professors and the students were playing with ether too. So they were doing these ether parties and you'd get together with your professors and like get high on ether. Times have changed.

No, no, no, I do that all the time in my classes, yeah, absolutely. Oh, yeah, I don't, we're moving on. So if any administrators at UC Irvine are listening, that was a joke, of course. Good, yes, yes. So I think Morton had been aware of what Wells was doing, and he starts using ether instead of nitrous oxide. He talks to his chemistry professor. He's like, can you get me some ether? And to try out the ether, Morton wasn't willing to test on himself.

He extracted the tooth of one of his assistants. Oh. But the ether he was using wasn't pure enough, and it was painful for the assistant. So Morton's like, oh, shoot. So then he starts testing on himself because he can tinker with the doses and the purity. And apparently his wife is like super not excited that he's doing this because he's like, I set a timer and I knocked myself out for eight minutes. And she's like, no.

That's not good. That's not good. What are you doing? You're getting drain, brimage. Oh, God. So later he tries it out on a patient who has a toothache, and it works great. So he also goes to Massachusetts General Hospital in 1846, and there is a surgeon who is doing a procedure to excise a neck tumor.

At the time, Morton was a second-year Harvard medical student, and he gets permission to administer ether while the surgeon is removing the tumor. And the procedure goes so well that when it's done, the surgeon looks out at the audience and says, gentlemen, this is no humbug. Wait, you have to translate for me. is that good? Humbug is bad, so no humbug is good? That's right, yes. Yeah, the double negative threw you a bit.

So if you're getting comments from a reviewer in the 1800s, and a reviewer, too, is like, this paper is no humbug, then that's good. That's good, yeah. You probably got past reviewer, too. Good job. So it worked. But Morton at this point sees a cash cow, and so he doesn't want to tell anybody what it is. And so he names it Letheon, which is after the mythological river Lethie, I think it's pretty where the souls of the dead forget their earthly lives. I don't know if I'd want to be taking something that's usually associated with helping the dead forget things.

Like, I'd rather stay alive while I forget the procedure. Would you like to take a trip on the river sticks? Yeah, no, thank you. I'll pass. Can you just take this molar out, please? That's one big humbug for that idea. That's right, amen. But ether has a super distinct smell,

and so surgeons pretty quickly figured out what he was doing. And he tried to get money some other ways. He tried to make this like very particular device for administering the ether, but other people figured out better devices. And so anyway, eventually Morton realizes he's not going to make a ton of money. And everybody now transitions to trying to figure out who can get the most credit for it. So if you're not going to get rich, at least you can impress the whole world, right? Here comes the dark side of science. That's right.

Here we go. So Wells, who was the first to do a public demonstration of it. And if you remember, he's the one where he did the public demonstration, it didn't work. was super embarrassing. So Wells is interested in this, but he's trying out some other ways to maybe make it work better because it was embarrassing when he did the nitrous oxide thing. So he starts trying chloroform instead. But he gets addicted to the chloroform and it seems to have eventually like sort of messed with his mental health, messed with his mind. So he goes to jail for throwing sulfuric acid on prostitutes. Oh boy. Yeah. And while he's in prison,

he had apparently managed to smuggle some chloroform in, and he commits suicide using the chloroform and a razor blade in prison. And the worst, well, not the worst. The worst thing is he died. That's awful. But his wife, a few days later, gets a letter from the Paris Medical Society, and they have concluded that Wells is the one who should get credit for doing the first painless surgery under anesthesia.

Oh, no. So that letter could have saved his life. Probably, yeah. It seems like he was super concerned about the credit. Anyway, so next up we'll talk about Morton. Well, that's a big humbug. That is a huge humbug. Humbug of the year, maybe.

Yeah. Yeah, so Morton is the guy who was trying to make a bunch of money off of ether, and he had kind of worked with his chemistry professor, and he and his chemistry professor, it turns out, end up in this giant debate about who should get the credit. And Morton, as I mentioned, he had this device that people stopped using, and then he's frustrated because other dentists are using this procedure, so now he's not even making money by having the most patients.

In the meantime, a lot of people are now having surgeries and procedures without pain, so that's good. That should be huge, right? Yeah. But that's not doing it for him. And in 1868, a magazine article comes out saying that Morton's professor, Jackson, is the one who should get the credit. And that seems to drive Morton absolutely crazy. And he drives to New York to confront the editors and dies of a stroke in Central Park. Oh, my gosh.

At 48. This whole area is like cursed. I know. It's horrible. Or maybe it's just a problem. of all this self-experimentation with these crazy drugs? I mean, I do think that the fact that these drugs are a bit mind-altering and had been used maybe way too often and at way too high doses

could have had something to do with the mental health problems these people had. But anyway, Jackson, the chemistry professor, is backed by the Academy of Sciences of the Institute of France. So it looks like the medical communities in France are sort of divided on who they're going to back. Jackson gets told that he's getting the credit, but he becomes an alcoholic and he's found screaming at Morton's gravestone. Like, even after Morton dies, he's still angry enough to, like, go to his gravestone and yell at him.

He ends up in an asylum where he stays for 12 years and dies at 75. I hope to never be found yelling at a gravestone. Yeah. Like, wow. No, me too. That seems, that's pretty high end. Like, at the point where your enemy has passed on, I feel like you should move on. But I guess it's not always that easy.

On the other hand, gravestones are kind of there for you to, like, visit someone's who's past and talk to them and connect with them. And so if Yellen's what you got to do, I guess that is the place for it. Yeah, I guess, sure, sure. But maybe I'd want to, like, smoke some banana peels to chill me out before I get there. Yeah. But I'm also intrigued by this facet of history where, like, societies are deciding who gets credit for something. Yeah. You know, that's not the way we do things these days, at least not in physics.

Like, if you make a discovery, you argue about the paper or you argue about who gets prizes. But it's never like the American Physical Society decides Daniel gets credit for this idea or Sally gets credit for that idea. I mean, I feel like the Nobel Prize has just, like, that is the ultimate arbiter of who gets credit for the idea. And maybe nobody else minds, I guess. Or nobody else feels like it's worth weighing in. I don't know. Yeah. Yeah, I guess this is all pre- Nobel Prize stuff.

So maybe that plays a role. Fascinating. All right. So, so far, three folks have tried to take credit for it and either died or gone mad. Who's up next? I saved the best for last. So remember the first, no, no, this is actually the best. So the first person who we talked about, who didn't share his results publicly and was just like, oh, this is great. I'm going to make sure that all of my patients are well taken care of from here on out. He continues his medical practice, owns a pharmacy in Georgia, and has a happy life.

Oh, my gosh. I was waiting for the disaster there, but I'm glad he lives happily ever after. Well, he dies at 62. He dies well prepping to give ether to a woman in labor, so that wasn't great for her. I'm sure she was like, no, at first give me the ether. That's not a good sign if your doctor drops dead during labor. No, no. But actually, before we go to a commercial, I want to real quick tell you this story about chloroform in the UK.

So the UK was more interested in chloroform. we were more interested in nitrous oxide and ether. And a very important time when you can use ether is during childbirth. So there was the Scottish obstetrician James Simpson. We talked about this guy in the intro. He ran out of the operating theater and thought about becoming a lawyer because it was so upsetting to watch surgeries without ether. But anyway, around 1847, he's experimenting with different gases, decides chloroform is best. But there was this idea at the time that women needed to actually go through the process of labor and that the pain was sort of

part of it and taking the pain away was unethical or like wasn't okay on religious grounds. Wow. And so he wasn't able to start administering it widely until John Snow and any epidemiology nerds out there are like John Snow with the with the cholera pump and the Broad Street pump. But anyway, so he helped figure out the cause of cholera. I think the pandemic was wrapping up by the time he figured it out. He in 1853 administers chloroform de Queen Victoria while she's giving birth to her eighth child. That's high stakes. That's super high stakes. But it goes great. Queen Victoria is like,

awesome. Everyone should have access to this. And now it becomes super widespread. It has since been sort of superseded by other methods because it is kind of nasty stuff. And if you use it for too long, it damages like the liver, kidney hearts. And eventually chloroform falls out of favor. But Queen Victoria and obstetrician James Simpson helped bring some pain relief to to women in childbirth. Hurrah. Harrah, James, and Green Victoria. It's amazing how these things are cultural, right? How, like, one person in one country can turn a whole society in one direction or another to use chloroform or nitrous oxide.

It's incredible how random history really is. Oh, my gosh. Yeah, it absolutely is. Agreed. All right. Well, let's take a break. And when we come back, we'll learn what we do and don't know about how anesthesia actually works. Welcome to Pretty Private with Ebeney, the podcast where silence is broken and stories are set free.

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And let's just clarify there's different kinds of anesthesia in this episode. We've been talking about general anesthesia where you breathe it in and it totally knocks you out. You feel no pain. We're going to go into a bit more detail about that. Well, you don't remember feeling pain, right? Isn't there still some debate about like, are you actually feeling pain? But then the experiences are wiped from your memory. And so it's like you didn't feel pain.

If you're taking a local anesthetic, you are awake. And so, like, when I got an epidural when I was giving birth to my second kiddo, I was awake, you know, but I didn't feel any pain. I felt very itchy, but I didn't feel any pain. And he was a 10-pounder. And so I don't think that my memory was wiped, because if so, I would have been feeling pain in the moment. Right, but general anesthesia you're not conscious of, right? So it's possible that you are aware of the pain, you just don't remember it, right? Because in general, I see, you don't remember the procedure.

Yeah, I think there is a subset of people who, like, will wake up sometimes, and they can't move. Yeah. But I don't think they feel pain. They're just like, this is a very disconcerting experience. Well, let's hope not. But it strikes me that, like, if I went through a very painful experience and then somebody came and deleted those memories, I wonder how that would be different from the experience of general anesthesia, right? Yeah, I don't know. Anyway, maybe that's more a philosophy question.

But tell us what we know about how this actually works medically and neurologically. Not a lot. So the proceedings of the National Academy of Sciences is a big prestigious group of scientists in the United States. And a 2020 paper started by saying, anesthetics are used every day in thousands of hospitals to induce loss of consciousness. Yet scientists and the doctors who administer these compounds lack a molecular understanding for their action. This is 2020. So we're not talking about ancient history anymore. This is basically today.

That's right. That's where we are. But another thing that was sort of interesting is that, they mentioned in 1846, William Morton demonstrated general anesthesia with inhaled anesthetic diethyl ether. So apparently they picked Team Morton. Like, I don't know if they, you know. They're waiting into this controversy. That's right.

That's right. But anyway, they're giving credit to him. Well, I hope that the descendants of these four gentlemen are not like still battling it out. I hope they get together and toast these guys and all their achievements and all get along. I think it would be much nicer to just appreciate the memory of. of people who took pain away for so many of us as opposed to like turning it into a nasty fight for credit. But anyway, okay, so I ended up reaching out

to two different anesthesiologists because it was really complicated working through the literature. And I couldn't tell if I was reading sort of fringe ideas or the main idea. And so I ended up talking to Dr. Shannon Stem and Dr. Ajoa Botan Evans. So the main mechanism that we think is important here is a neurotransmitter called GABA

Aminobutyric Acid or just GABA. Okay. Your neurons have receptors, and these receptors are responsible for tinkering with the electrical charge inside of the neuron. So let's talk about why that's important. So our neurons are connected to each other.

There's like this open area in between neurons called the synapse, and when chemicals are released into that synapse, one cell has talked to another and a message passes between the neurons. The way you get that message into the synapse is that your cell needs to pass a certain electrical charge to initiate what's called an action potential.

So usually your neuron has a little bit of a negative charge. And when it starts to accumulate a positive charge, at some point it'll pass a threshold, an electrical charge will pass through the neuron, the chemicals will get released into the synapse, and the conversation between neurons will happen. This is fascinating to hear about because I think about neurons all the time, but from the point of view, artificial neural network. I do a lot of machine learning and AI, and we use neural nets all the time. But we never think about them as neurons anymore.

But we use the same language. You know, our mathematical model is that a neuron is like a little blob and it has inputs. And if the inputs are high enough that they add up to a certain amount, then the neuron is activated and it sends a pulse to its output, which is linked to other neurons, of course. And my understanding of the brain, basically, is that it's this big network of neurons that are all firing and stimulating each other. And so you're talking about the bit between the neurons, the synaps, the connection, and whether that thing is allowed to fire or is inhibited from communicating with other neurons. Is that right? Yeah, pretty much. I mean, we're focusing on the neurons too. So what GABA does is it inhibits the action potential. So what essentially happens is that your neuron has all of these receptors on it. And it has three different kinds of GABA receptors. For two of them, when this chemical GABA binds, they open up and they let chloride ions in. And so these ions have a negative charge. And so the negative charge in the neuron gets more negative, which makes the cell less likely to hit that action potential point and talk to the next neuron.

I see. There is another kind of receptor that when GABA binds to it, it opens up and it lets potassium ions out. And these are positive charge. So the positive charge is fleeing. And so here again, the cell is getting more negative, but just through a slightly different mechanism. So in all of these cases, GABA. is making the cell more quiet, less likely to communicate with the next cell down the line. And it's just like a hypothesis or something we can observe by taking like a single neuron and

putting it an experiment and, you know, connecting it to electrodes? So I can't say that I am an expert in how we know this. One of the women that I talked to did mention that there was some experiments done in mice where they genetically tinkered with the mouse so that their GABA receptors were, We're kind of messed up. And when you do that, anesthesia doesn't work the same way in these mice. So that's pretty good evidence that GABA is somehow involved in anesthesia. But in terms of what we know about what these neurons are doing in our brains in response to GABA,

like I don't know that we've been able to observe that happening in real time. Yeah, although the system is so complicated, it's hard to draw conclusions, right? There's the famous example of the scientist who trains frogs to jump when he says jump. and then it cuts their legs off, and he says, jump, and they don't jump. And it's like, oh, see, they can't hear me. So therefore, they must hear with their legs. Yeah. Right.

Like, you can obviously draw the wrong conclusion when you're dealing with a complex system. Was that a ridiculous example? Yeah. What famous experiment is that? I've never... It was not a real experiment. It's a famous anecdote illustrating how you can draw the wrong conclusion from your data. Ah.

Even if it sounds reasonable, right? So in this case, you're saying, like, it interferes with a GABA, and the anesthetics don't work the same way. And that is suggestive, but I don't know how. conclusive it is. Yes, absolutely. I agree. And further highlighting the fact that we don't really know what's going on, we've looked at the structure of the chemicals that are used as general anesthetics. And based on the chemical structures, we've tried to predict other kinds of chemicals that should also act as anesthetics because we think we understand what's going on. And some cases

that works and other cases it doesn't. So there's something we don't understand. Also, Dr. Shannon Stem was telling me that xenon kind of has similar. characteristics when you give it to people, like it acts as an anesthetic, and xenon is a noble gas, so it's not supposed to be reacting with anything. So what the heck is happening there? We don't know. Maybe it just interferes, right? Zenon can also, like, kill you because you can breathe it in and it can interfere with you breathing oxygen, right? So maybe it just gets in the way. Yeah, yep. Maybe it does just get in the way. And then it also seems like the function of some of the different kinds of anesthetics that we try is making cells more excitatory, so more likely to

talk to each other. And so I saw what appeared to be a hypothesis where the idea was just that it messes up communication. So instead of having like a clear signal traveling from neuron to neuron, there's just all kinds of things communicating with each other at weird times. And it's more about like the pattern of communication getting thrown off. But anyway, I want to make clear that anything that I have gotten incorrect is my fault and not the fault of the anesthesiologists who very patiently tried to explain this all to me. And how terrified do you think they are by not really knowing how this works. Doesn't that make it something of an art for every patient?

You have to really monitor them. Maybe they're reacting differently because you can't always predict, right, how much anesthetic somebody's going to need. Yeah, so they both highlighted to me during our conversations how amazing the monitoring equipment is now. So, yes, you do need to be careful. Some people need more. Some people need less.

Some people have strong reactions. But they're monitored very carefully. And as long as the people know what they're doing, you know, and I'm sure hopefully all certified anesthesiologists do know what they're doing. You know, they felt like it would be good if we knew the mechanism. Maybe that would help us become even better at this stuff. But they felt like not knowing the mechanism didn't keep us from doing a good and safe job. And I feel like there's got to be all kinds of physics stuff that you apply, that even though you don't understand it at like atomic level or whatever, you can still form predictions and, you know,

do amazing new experiments. Oh, for sure. There's so many cases where we don't understand the microphysics, or it's too complicated for us to model, that we know generally how things behave. And so absolutely, you don't need to know all the details. I'm just super curious. And, you know, somebody's life is at stake here. And so it seems pretty important. You get a sense from them, like, what is the cutting edge? Are we going to, in 10 years, develop new amazing anesthetics that are better or safer or transcendently wonderful or something? What are people working on? I didn't get a clear answer on that. They did mention, in passing, again, how great great. We are getting at monitoring and how we're getting a better understanding of how people from different backgrounds respond differently to anesthesia so that we can try to make things even safer for everyone. My conversations with Shannon highlighted that they are trying to predict different compounds that would make good anesthetics and they're trying those out. So maybe we'll even have better tools in the future. But if they were here, they might give a much better answer.

No surprise. So the final question we got from the listener is, is going under anesthesia different than sleeping, or is it the same? And it's definitely different than sleeping. So the anesthesiologist I talked to said that it's more like a drug-induced reversible coma. Whoa. Yeah. So the main criteria are that you want the person to be unconscious, not feeling pain, not moving, and making no memories. So when you're sleeping, one, you move.

people sleepwalk sometimes. Right. Two, if somebody were to poke you, you would feel pain. Three, as I understand it, the main function of sleep is that it helps us consolidate memories and sometimes you even remember the dreams that you had, whereas when you are knocked out under general anesthesia, you don't make any memories. Wow. Additionally, when you are sleeping, when you do an EEG, you're looking at the activity in your

brain and you'll see that we alternate between two different kinds of brain waves. So when we're in rapid eye movement sleep, our brains are doing one thing. And when we get out of rapid eye movement sleep, our brains are doing something different. And we're going to probably go into a lot more detail about this in a future episode because we're getting Dr. Gina Poe on the show to tell us all about sleep and why we sleep. So more on that later. But the point is that when we're sleeping, our brains are sort of alternating between two modes. And when you go under anesthesia, you are staying in the same mode the whole time. And I believe it also just like creates different sort of electrical patterns all.

together. So there's really no way in which it's sleep. And this is, we can sort of end on a moderately interesting story, which is Michael Jackson used to take this drug called Propophal. And it's an anesthetic. It helped knock him out and it made him feel good. And so he was given it by his doctor at night to help him sleep. Because he had sleep problems, right? Okay. Yeah. But it's not actually sleep. So all of the important things that your body does while you're sleeping are not getting done, they're not getting done as well when you're knocked out by something like propofal. And so part of why it's thought that he ended up dying was because he was laying down, but he was actually over time being deprived of sleep.

Oh, my God. So it is different than sleep in a way that is very meaningful and important. It's amazing how vital and how crucial all these brain functions are, how little we understand them, and yet how much we rely on all these medical advances to manipulate them. Yeah, it's incredible. You know, despite the fact that we don't really understand this at a mechanistic level, I am still on team anesthesia. I would not want to live in any time that didn't have it. And, you know, in addition to not needing to be like literally pinned down and restrained while someone cuts into you for surgeries,

anesthesia opened up much longer, much more complicated surgeries. And it has, I'd say, really changed our lives in a lot of great ways. Yeah. And it's so recent, right? Until just a couple hundred years ago, surgery. was horrible suffering. Makes me wonder what medical advances in a few years or a few hundred years people will be unable to live without or imagine what it was like before we had them.

Yeah, no, it's incredible. I mean, I had to have my wisdom teeth out. I can't imagine someone just yanking those out with pliers without being knocked out. And clearly, that is one of the easier surgeries to do. I've never had someone to cut into my abdomen, for example. Right. So, hurrah for living today. All right.

Well, we hope that journey into the history of anesthesia didn't put you all to sleep or numb your brain. It couldn't have. It was fascinating. Some folks like to listen to the podcast to fall asleep. So we hope that they're now asleep pleasantly. Have a great night, everyone. Sleep tight. And let's end by hearing what Eric thought about our, hour-long episode on anesthesia.

Eric? That definitely answered my questions. I went to college in Atlanta, so I think I'm definitely going to have to be on Team Cross. Crawford Long in the great anesthesia wars, and I admit to a little disappointment that I was born too late for ether parties and too early to live in a city on Mars, but I do live in the golden age of podcasts. So thank you so much, and have a great day. Daniel and Kelly's Extraordinary Universe is produced by IHeart Radio. We would love to hear from you. We really would. We want to know what questions

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And we're best friends and journalists with a new podcast called No Such Thing, where we get to the bottom of questions like that. Why are you screaming? I can't expect what to do. Now, if the rule was the same, go off on me. I deserve it. You know, lock him up. Listen to No Such Thing on the IHeart Radio app,

Apple Podcasts, or wherever you get your podcast. No Such Thing. I'm Dr. Joy Harton-Bradford, host of the Therapy for Black Girls podcast. I know how overwhelming it can feel if flying makes you anxious. In session 418 of the Therapy for Black Girls podcast, Dr. Angela Nealbarnett and I discuss flight anxiety. What is not a norm is to allow it to prevent you from doing the things that you want to do, the things that you were meant to do. Listen to Therapy for Black Girls on the IHeart Radio app, Apple Podcasts, or wherever you get your podcast. Betrayal Weekly is back for season two with brand new stories.

The detective comes driving up fast and just like screeches right in the parking lot. I swear I'm not crazy, but I think he poisoned me. I feel trapped. My breathing changes. I realize, wow, like he is not a mentor. He's pretty much a monster. But these aren't just stories of destruction. They're stories of survival. I'm going to tell my story and I'm going to hold my head up.

Listen to Betrayal Weekly on the IHeart Radio app, Apple Podcasts, or wherever you get your podcasts. Hi, it's Gemma's Begg, host of the Psychology of Your 20s. This September at the Psychology of Your 20s, we're breaking down the very interesting ways psychology applies to real life, like why we crave external validation. I find it so interesting that we are so quick to believe others' judgments of us and not our own judgment of ourselves. So according to this study, not being liked actually creates similar pain levels as real life physical pain.

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