Saturday Matinee: Daniel and Kelly’s Extraordinary Universe

Summary

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History Daily: Saturday Matinee — Daniel and Kelly’s Extraordinary Universe

Episode Title: The History and Mysteries of Anesthesia
Release Date: February 7, 2026

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Episode Overview

This special Saturday Matinee episode, handpicked by History Daily's host Lindsay Graham, features an episode from Daniel and Kelly’s Extraordinary Universe. Daniel (a particle physicist) and Kelly Wienersmith (biologist, space and parasite specialist) dive into the surprisingly recent, sometimes wild, often tragic, and still-mysterious story of anesthesia—how humans have tried to dull surgical pain, the pivotal discoveries and dramas that shaped modern medicine, and just what we do (and mostly don’t) know about how anesthesia works on the brain.

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Key Discussion Points & Insights

1. The Horrors of Surgery Before Anesthesia

[05:17] Kelly Wienersmith gives a vivid, sometimes gruesome account of what it was like to undergo surgery before the advent of anesthesia.

• Early surgical practices: Patients were held down, surgeons prized for speed rather than precision, surgeries done in minutes.
• Blood, pain, and aftermath: “Not only was it an absolutely miserable experience to be held down by surgeon assistants while you were cut into, but if that experience didn't kill you, subsequent infection often did.” (Kelly Wienersmith, 07:16)
• Memorable story: Dr. Robert Liston's ultrafast amputations, sometimes leading to horrific mistakes (e.g., a testicular amputation by accident).
• Physician James Simpson’s reaction: Fled a surgery in horror; would later pioneer anesthetics in childbirth.

2. Personal Anesthesia Anecdotes

[09:10]

• Daniel: Most terrifying experience was his son going under anesthesia: “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?” (Daniel, 09:34)
• Kelly: Shares post-anesthesia embarrassment: “After I came out of a procedure, I just kept asking, was I polite to everyone?...and then I threw up, but I didn't feel the procedure, which is great.” (Kelly Wienersmith, 10:21)

3. How Did People Manage Pain Before Modern Anesthesia?

[16:01]

• Ancient physicians tried various mixtures—inhaled drugs, alcohol, lost-to-history recipes.
• French surgeons literally knocked people out with mallets; hypnotism/mesmerism briefly attempted.
• Wild anecdote: “French surgeons...would knock people out not with drugs, but by putting a wooden bowl over someone's head and hitting it with a hammer.” (Kelly Wienersmith, 16:39)
• Humphry Davy (1799) realizes nitrous oxide could kill pain—instead, enjoys partying, moves on, and the insight lies dormant for decades.

4. The Ether & Nitrous Oxide “Party” Years

[21:45]

• “Ether frolics” and “laughing gas parties” popular amusements before anesthesia’s surgical potential was realized.
• Ether and nitrous oxide became recreational drugs, not medical miracles at first.
• When abused, ether and chloroform could drive users mad.

5. The Race for Credit: Four Pioneers and a Tragedy of Egos

[28:04–41:22]

Four Main Figures:

• Dr. Crawford Long: Observes painlessness at ether parties, first to use in surgery (1842), but doesn't publicize results, lives a quiet, long life.
• Horace Wells: Dentist, experiments on himself with nitrous oxide, fails a public demonstration (insufficient dose), is humiliated; later addicted to chloroform and dies tragically by suicide in jail.
• William Morton: Dentist and entrepreneur, tries to monetize “Letheon” (rebranded ether), public demo at Massachusetts General; obsessed with credit, dies of a stroke after controversy.
• Dr. Charles Jackson: Morton’s chemistry professor, claims credit, becomes an alcoholic, later institutionalized after being found yelling at Morton’s grave.

Notable Quote:
“Jackson gets told that he's getting the credit it, but he becomes an alcoholic and he's found screaming at Morton's gravestone.”
— Kelly Wienersmith [39:04]

Public Demonstration Gone Wrong

• Horace Wells’s failed demo: “He decides he's going to remove a tooth from a volunteer, but he doesn't give the volunteer enough nitrous oxide. And so now the patient is clearly feeling pain during this procedure. And it is very embarrassing…” (Kelly Wienersmith, 33:06)

A Happy Ending - Sort of

• Dr. Crawford Long never seeks the spotlight: "The first person...continues his medical practice, owns a pharmacy in Georgia, and has a happy life." (Kelly Wienersmith, 41:22)

Culture Shift: Queen Victoria, Childbirth, and “Chloroform an’ all that”

• Use of chloroform in childbirth (Scotland & UK), thanks to Queen Victoria’s public endorsement (administered by Jon Snow): “Queen Victoria is, like, awesome. Everyone should have access to this. And now it becomes super widespread.” (Kelly Wienersmith, 42:49)
• Overcoming religious and moral objections to pain relief in labor.

6. What We Actually Know—and Don’t Know—About How Anesthesia Works

[43:49–55:36]

• Despite daily use in hospitals, the molecular mechanism remains elusive.
  • “Anesthetics are used every day in thousands of hospitals...Yet scientists and the doctors who administer these compounds lack a molecular understanding for their action.” (Kelly Wienersmith, quoting 2020 PNAS paper, 47:44)
• Role of GABA neurotransmitter:
  • Acts as an inhibitor—makes neurons less likely to fire, hence, dulling consciousness.
  • Analogy: Daniel draws parallels to artificial neural networks.
• Experiment evidence: Mice with manipulated GABA receptors react differently to anesthetics.
• The chemical structures of anesthetics are diverse and sometimes unpredictable; cases like xenon challenge the dominant models.
• The unpredictability and patient-to-patient variability are why modern monitoring is so crucial.

Daniel, on the discomforting unknowns:
"Doesn't that make it something of an art for every patient? You have to really monitor them. Maybe they're reacting differently, cause you can't always predict...how much anesthetic somebody's gonna need." (Daniel, 54:37)

7. Is Anesthesia the Same as Sleep?

[56:50]

• Clear answer: It is NOT sleep.
• Anesthesia is pharmacologically more like a reversible coma—no memory formation, no pain, no movement, very different brainwave patterns from regular sleep.
• “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...if somebody were to poke you, you would feel pain...when you are knocked out under general anesthesia, you don't make any memories.” (Kelly Wienersmith, 57:20)
• Michael Jackson’s case: Use of propofol for sleep cost him actual restorative sleep and likely contributed to his death.
• General anesthesia enables modern surgery, supports longer, more complicated procedures, and fundamentally changed survival and medicine.

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Notable Quotes & Memorable Moments

• On the early days of surgery:
  “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...he often started his surgeries by proclaiming 'time me, gentlemen. Time me now.’” (Kelly Wienersmith, 06:04)

• Daniel (on medical uncertainty):
  "I'm more terrified, I guess...our bodies are huge Rube Goldberg machines, and we don't know how they work." (Daniel, 11:50)

• Kelly (on ether frolics):
  “They’d get together, huff ether and appreciate how awesome it made you feel.” (21:45)

• On the drama of discovery:
  "Morton realizes he's not going to make a ton of money...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?" (Kelly Wienersmith, 36:27)

• Kelly, summing up:
  “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.” (Kelly Wienersmith, 59:00)

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Timestamps for Important Segments

• 05:17 – The horrors of surgery before anesthesia; Dr. Liston's "time me" approach
• 09:10 – Daniel & Kelly’s personal anesthesia stories
• 11:08 – Listener question launches the historical journey
• 16:39 – Knocking patients out with a mallet; early methods
• 17:44 – Humphry Davy and missed opportunity with nitrous oxide
• 21:45 – “Ether frolics” and recreational use
• 28:04 – 41:22 – The pioneers, the race for credit, and the tragedies that followed (Wells, Morton, Jackson, Long)
• 42:42 – Queen Victoria & the spread of chloroform in childbirth
• 46:19 – 55:36 – What we know (and don’t) about how anesthesia works: GABA, experiments, unpredictability
• 56:50 – Sleep vs. anesthesia, Michael Jackson anecdote
• 59:00 – The life-changing importance of anesthesia

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Tone & Style

Friendly, funny, and highly conversational—all while being deeply informative. Daniel and Kelly keep the tone engaging with anecdotes, banter, playful jabs at chemists, and relatable personal experiences.

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Final Thoughts

This episode provides a riveting look into the painful, messy origins of surgical anesthesia, explores the scientific mysteries that remain, and highlights the sometimes tragic human stories that propelled medicine forward.
As Kelly sums up: “Hurrah for living today.”

Transcript

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[History Daily Host]

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[Kelly Wienersmith]

Hello friends. 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 van Leeuwenhoek 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 Russel 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 Fitzharris 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 21, 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 assistants 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 him out. The leg was quickly sawed 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.

[Daniel]

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.

[Kelly Wienersmith]

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, never been scared about it. What, what was so scary about your kid going under?

[Daniel]

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?

[Kelly Wienersmith]

But Daniel, it's more than just a pretty good chance. Like, we've got a lot of experience with this by now.

[Daniel]

Yeah, we have played Russian roulette 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.

[Kelly Wienersmith]

Yep. Have you ever said anything particularly stupid coming out of anesthes?

[Daniel]

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?

[Kelly Wienersmith]

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. Zach said I was fine and then I threw up, but I didn't feel the procedure, which is great.

[Daniel]

Well, I'm sure you're always polite, Kelly, even when you're in pain or when you're out of it.

[Kelly Wienersmith]

Thanks. Yeah, Apparently, I really worry about that.

[Daniel]

And I'm sure that today you're going to give us 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.

[Kelly Wienersmith]

Yes. Well, I am attempting today to politely answer a wonderful question from our listener Eric. And let's go ahead and heat hear that question now.

[Listener Eric]

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.

[Kelly Wienersmith]

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 [e-mail] this question makes me.

[Daniel]

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 know, 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 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. Yeah.

[Kelly Wienersmith]

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 brain 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?

[Daniel]

I know, I know. And the physicist, to me, wants to be, like, really reductionist and be like, we have to understand how these things work if we're gonna 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 gonna do? Have we basically just been experimenting on ourselves unethically, on other people for millennia? Like, this is terrible. On the other hand, you 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.

[Kelly Wienersmith]

So. Yeah, yeah, well. And so that's actually a really nice transition into a book that I use 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 experimentation in 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 experimentation in the history of anesthesia.

[Daniel]

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?

[Kelly Wienersmith]

All right, 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 Nazi 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.

[Daniel]

Oh.

[Kelly Wienersmith]

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 a hundred subjects and the first one is gonna 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.

[Daniel]

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.

[Kelly Wienersmith]

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, you know, trials for vaccines. Yeah, not anymore. These kinds of data would not fly anymore, just to be clear. Okay, 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 1, but then you need to follow it up with much better, much more broad trials.

[Daniel]

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?

[Kelly Wienersmith]

So I don't know many thousands of years ago, but something like 1 to 2000 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.

[Daniel]

The physicians were doing drugs and that helped them with the surgery or the patients were getting the drugs?

[Kelly Wienersmith]

No, if I needed to amputate someone's limb, maybe I would want to be. Not completely present for that process, but.

[Daniel]

Like, pass the pipe there, dude, when you're done with it.

[Kelly Wienersmith]

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.

[Daniel]

Oh, my gosh.

[Kelly Wienersmith]

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 Humphry Davy, was he a physics guy?

[Daniel]

I don't know. I never heard of him.

[Kelly Wienersmith]

Oh, gosh, I heard his name before and I just assumed he was a physicist.

[Daniel]

Why did you assume he was a physicist?

[Kelly Wienersmith]

Because people don't care about old biologists.

[Daniel]

He sounds to me like a guy who would sit on a wall and then fall off and crack.

[Kelly Wienersmith]

Yep, yep. Oh, he's a chemist. Oh, God. All right.

[Daniel]

Yeah, knock him off that wall.

[Kelly Wienersmith]

That's right. That's right. So in 1799, Humph 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 Coolidge and Dr. Peter Roget, who was the guy who compiled 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, remove pain. But then he goes on and does other stuff, like he gets knighted for inventing the miner 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.

[Daniel]

Oh, my gosh. What are you doing keeping secrets of painless surgery from the masses?

[Kelly Wienersmith]

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.

[Daniel]

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, like, avoided necessary surgeries because they were just like, yeah, it's just not worth it.

[Kelly Wienersmith]

Yeah. So literally, you would be, you know, you 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 Fitzharris 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 and bonus, 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.

[Daniel]

Right. Maybe it's more of a last ditch option.

[Kelly Wienersmith]

Oh, God. Yeah, well.

[Daniel]

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?

[Kelly Wienersmith]

So the earliest record that I came across while doing the research was 200 CE 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.

[Daniel]

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.

[Kelly Wienersmith]

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 happens. So I don't know that I'd want an ancient Egyptian surgeon to be working on me.

[Daniel]

All right, so let's fast forward back to the present. You said Humphrey Davy missed his opportunity to save people from pain and just enjoyed hanging out with his friends Sam Coleridge and Peter Rajat. What happened next? When did we actually start to figure stuff out and use it to save people from suffering?

[Kelly Wienersmith]

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 ether frolics 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.

[Daniel]

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 in the late 1800s. That's not what people are snuffing at your biology parties, right?

[Kelly Wienersmith]

No. A chemist would tell you that ether is an organic compound. It's a mix of oxygen with alkyl groups. And, you know, we both know that. I don't know much about chemistry, but no, it's not a made up idea. It is. It's an actual chemical compound.

[Daniel]

And what happens when you sniff it? You just, like, feel good or you pass out or what happens?

[Kelly Wienersmith]

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 hurts stopped hurting. And you'd laugh a lot more and, you know, that all sounds fantastic.

[Daniel]

That sounds great. Why did it go out of fashion?

[Kelly Wienersmith]

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 taking.

[Daniel]

Probably chemists.

[Kelly Wienersmith]

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 to for credit for being the first to come up with this idea.

[Daniel]

Oh, no.

[History Daily Host]

History Daily is sponsored by quints. The difference between stuffing a closet and building a wardrobe is all about pieces that work together and hold up over time. That's what Quince does best. Premium materials, thoughtful design, and everyday staples that feel easy to wear and easy to rely on even as the weather shifts. And boy, can the weather shift Here in Dallas, we went from 50 to zero in just two days, so layers are important. Organic cotton sweaters, polos for every occasion, lighter jackets and thicker coats. Quint's has them all, working directly with top factories and cutting out the middlemen. So you're not paying for brand markup, just quality clothing like the pieces we outfitted our daughter with. A new hoodie, some wide leg, fleece pants, and even a bracelet that she's yet to take off. So refresh your wardrobe with Quince. Go to quince.comhistorydaily for free shipping on your order and three 365 day returns. Now available in Canada too. That's Q-U-I-N-C-E.com historydaily free shipping and 365 day returns. Quince.com historydaily if you're an H VAC.

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[Kelly Wienersmith]

All right, we're back. We were talking about aether parties which do sound fun, but I would not engage in an ether party because I'm.

[Daniel]

A wimp and you're so wholesome.

[Kelly Wienersmith]

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. But that's fine. I'm not fun.

[Daniel]

You're a lot of 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 Wienersmith]

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 rol.

[Daniel]

That's the modern day ether.

[Kelly Wienersmith]

What about you?

[Daniel]

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.

[Kelly Wienersmith]

Ah, well, we all have had youthful indiscretions.

[Daniel]

All right, so now let's talk about the indiscretions of various men in history who brought us anesthesia.

[Kelly Wienersmith]

So the first person we're gonna 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.

[Daniel]

Wow.

[Kelly Wienersmith]

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 were sort of sitting in the same room. So now, like, you know, if you've watched Grey's Anatomy, you know that there is, like, a elevated area, and you can be behind glass, and you can sort of peek in, like a splash.

[Daniel]

Guard there and make sure you don't get sprayed in the face.

[Kelly Wienersmith]

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.

[Daniel]

But I wonder if they used to pass around raincoats the way they do it, like SeaWorld in the first few rows, you know?

[Kelly Wienersmith]

Oh, so gross. I know. They used to put sawdust under the operating tables to absorb the blood. Oh, wow. 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. Which we don't do anymore.

[Daniel]

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 gonna do? This is before movies. Let's go see some legs get cut off.

[Kelly Wienersmith]

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 funsies.

[Daniel]

Yeah, that's what I was thinking.

[Kelly Wienersmith]

Yeah. And so I do think some people did come off the street 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?

[Daniel]

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.

[Kelly Wienersmith]

Oh, all right. Well, then maybe I would watch the amputation. You know, what else are you gonna do in London? So anyway, Long gets the ball rolling, but. 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. Hehehe. It would be so fun. And people would watch this and they're.

[Daniel]

Like, let's amputate your leg. Sure.

[Kelly Wienersmith]

Hehe.

[Daniel]

He. Lol.

[Kelly Wienersmith]

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, whoa, hey, I saw that someone got hurt, and then they were totally fine. 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?

[Daniel]

This is a dentist who cares, who doesn't want to cause his patient's pain.

[Kelly Wienersmith]

That's right.

[Daniel]

Amazing.

[Kelly Wienersmith]

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.

[Daniel]

I hope he listens to the pod and hears how much you love him.

[Kelly Wienersmith]

You're the best, Dr. Caton. 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. 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.

[Daniel]

So he just like, sacrifices a healthy molar to science?

[Kelly Wienersmith]

Yes. Yeah, he does.

[Daniel]

I like this dentist.

[Kelly Wienersmith]

Yeah, no, me too. He's willing to, like, get his hands dirty for the art. I appreciate that.

[Daniel]

All right, so far I'm voting for Horace Wells to get credit for this.

[Kelly Wienersmith]

I like Wells too. So Wells does this on 15 other patients and he decides. This is awesome, right?

[Daniel]

Yeah.

[Kelly Wienersmith]

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.

[Daniel]

Oh, no.

[Kelly Wienersmith]

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.

[Daniel]

This is his big moment. Wow.

[Kelly Wienersmith]

This was his big Moment. And we'll see that he doesn't actually emotionally recover from this. Oh, no, I know, I know.

[Daniel]

Some, like, emotional nitrous oxide. He needs some of that antidepressant.

[Kelly Wienersmith]

He does need some antidepressants, as we'll see. 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 and so.

[Daniel]

No, no, no. I do that all the time in my classes. Yeah, yeah, absolutely.

[Kelly Wienersmith]

Oh, yeah, I don't. We're moving on.

[Daniel]

So if any administrators at UC Irvine are listening. That was a joke, of course.

[Listener Eric]

Good.

[Kelly Wienersmith]

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?

[Daniel]

You're getting drain brain age.

[Kelly Wienersmith]

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.

[Daniel]

You have to translate for me. Is that good? Humbug is bad. So no humbug is good.

[Kelly Wienersmith]

That's right. Yes. Yeah, the double negative threw you a bit.

[Daniel]

So if you're getting like comments from a reviewer in the 1800s, and a reviewer too is like, this paper Is no humbug then. That's good.

[Kelly Wienersmith]

That's good. Yeah. You probably got past reviewer 2. 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 Lethier, which is after the mythological river Lethe, I think it's pronounced, 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.

[Daniel]

Would you like to take a trip on the River Styx?

[Listener Eric]

Yeah.

[Daniel]

No, thank you.

[Kelly Wienersmith]

I'll pass. Can you just take this molar out, please?

[Daniel]

That's one big humbug for that idea.

[Kelly Wienersmith]

That's right. Amen. But Aether has a super distinction, 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?

[Daniel]

Here comes the dark side of science.

[Kelly Wienersmith]

That's right. Here we go. So. 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. He 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.

[Daniel]

Oh, no.

[Kelly Wienersmith]

So he goes to jail for throwing sulfuric acid on prostitutes.

[Daniel]

Oh, boy.

[Kelly Wienersmith]

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. So. 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.

[Daniel]

Oh, no. So that letter could have saved his life.

[Kelly Wienersmith]

Probably, yeah. It seems like he was super concerned about the credit anyway, so next up we'll talk about Morton.

[Daniel]

Well, that's a big humbug.

[Kelly Wienersmith]

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 cause other dentists are using this procedure. So now he's not even making money by having the most patients.

[Daniel]

In the meantime, a lot of people are now having surgeries and procedures without pain. So that's good.

[Kelly Wienersmith]

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.

[Daniel]

Oh my gosh. At 48, this whole area is like cursed.

[Kelly Wienersmith]

I know, it's horrible.

[Daniel]

Or maybe it's just the product of all this self experimentation with these crazy drugs.

[Kelly Wienersmith]

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 it, 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.

[Daniel]

I hope to never be found yelling at a gravestone. Yeah, like wow.

[Kelly Wienersmith]

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.

[Daniel]

On the other hand, gravestones are kind of there for you to like visit someone who's passed and talk to them and connect with them. And so if yelling's what you gotta do, I guess that is the place for it.

[Kelly Wienersmith]

Yeah, I guess. Sure, sure. But maybe I'd wanna, like, smoke some banana peels to chill me out before I get there.

[Daniel]

Yeah. But I'm also intrigued by this facet of history where, like, societies are deciding who gets credit for something.

[Kelly Wienersmith]

Yeah.

[Daniel]

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.

[Kelly Wienersmith]

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.

[Daniel]

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?

[Kelly Wienersmith]

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 gonna 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.

[Daniel]

Oh, my gosh. I was waiting for the disaster there. But I'm glad he lives happily ever after.

[Kelly Wienersmith]

He does. Well, he dies at 62. He dies while 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.

[Daniel]

But that's not a good sign if your doctor drops dead during labor.

[Kelly Wienersmith]

No, no. But actually, before we go to a commercial, I wanna 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 the it. And taking the pain away was unethical or, like, wasn't okay on religious grounds.

[Listener Eric]

Wow.

[Kelly Wienersmith]

And so he wasn't able to start administering it widely until Jon Snow. And any epidemiology nerds out there are, like, Jon 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 to Queen Victoria while she's giving birth to her eighth child.

[Daniel]

That's high stakes.

[Kelly Wienersmith]

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.

[Daniel]

Hurrah, James and Queen Victoria. It's amazing how these things are cultural, right? How, like, one person in one country can turn a WHO society in one direction or another to use chloroform or nitrous oxide. It's incredible how random history really is.

[Kelly Wienersmith]

Oh, my gosh. Yeah, it absolutely is. Agreed.

[Daniel]

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.

[History Daily Host]

History Daily is sponsored by quintessential the difference between stuffing a closet and building a wardrobe is all about pieces that work together and hold up over time. That's what Quince does best. Premium materials, thoughtful design, and everyday staples that feel easy to wear and easy to rely on even as the weather shifts. And boy, can the weather shift. Here in Dallas, we went from 50 to zero in just two days, so layers are important. Organic cotton sweaters, polos for every occasion, lighter jackets, and thicker coats. Quince has them all, working directly with top factories and cutting out the middlemens. So you're not paying for brand markup, just quality clothing, like the pieces we outfitted our daughter with. A new hoodie, some wide leg, fleece pants, and even a bracelet that she's yet to take off. So refresh your wardrobe with Quint's. Go to Quint's.comhistorydaily for free shipping on your order. And 365 day returns now available in Canada, too. That's Q-U-I-N-C-E.comhistorydaily free shipping and 365 day returns. Quince.comhistorydaily if you're the purchasing manager at.

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[Kelly Wienersmith]

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[Kelly Wienersmith]

All right, so let's chat about what we know about how anesthesia works. 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.

[Daniel]

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.

[Kelly Wienersmith]

If you're taking a local anesthetic, you're 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 be feeling pain in the moment, right?

[Daniel]

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 generalistity, you don't remember the procedure.

[Kelly Wienersmith]

Yeah, I think there is a subset of People who, like, will wake up sometimes and they can't move, but I don't think they feel pain. They're just like, this is a very disconcerting experience.

[Daniel]

Well, let's hope not. But it strikes me that 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.

[Kelly Wienersmith]

Yeah. I don't know.

[Daniel]

Anyway, maybe that's more a philosophy question. But tell us what we know about how this actually works medically and neurologically.

[Kelly Wienersmith]

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.

[Daniel]

This is 20, 2020. We're not talking about ancient history anymore. This is basically today.

[Kelly Wienersmith]

That's right. That's where we are. But. But another thing that was sort of interesting is that they mentioned and 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.

[Daniel]

You know, they're wading into this controversy.

[Kelly Wienersmith]

That's right. That's right. But anyway, they're giving credit to him.

[Daniel]

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.

[Kelly Wienersmith]

I think it would be much nicer to just appreciate the memory of people who took pain away for. For so many of us, as opposed to, like, turning it into a nasty fight for credit. But, yeah, 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 Boateng Evans. So the main mechanism that we think is important here is a neurotransmitter called gaba, aminobuty acid, or just gaba.

[Listener Eric]

Okay.

[Kelly Wienersmith]

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, 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 the threshold. An electrical charge will pass through the neuron, the chemicals will get released into the synapse, and the conversation between neurons will happen.

[Daniel]

This is fascinating to hear about because I think about neurons all the time, but from the point of view of artificial neural networks, because I do a lot of machine learning and AI, and we use neural net, that's all the time, but we never think about them as neurons anymore. But we use the same language, you know, in 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 synapse, the connection, and whether that thing is allowed to fire or is inhibited from communicating with other neurons. Is that right?

[Kelly Wienersmith]

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 downwall.

[Daniel]

And is this like a hypothesis or something we can observe by taking, like, a single neuron and putting it in experiment and, you know, connecting it to electrodes?

[Kelly Wienersmith]

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 kind of messed up. And when you do that, 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.

[Daniel]

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 he cuts their legs off. 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.

[Kelly Wienersmith]

Yeah.

[Daniel]

Right. Like, you can obviously draw the wrong conclusion when you're dealing with a complex system. Was that a ridiculous example?

[Kelly Wienersmith]

Yeah. What famous experiment is that? I've never.

[Daniel]

It's not a real experiment. It's a famous anecdote illustrating how you can draw the wrong conclusion from your data, even if it sounds reasonable. Right. So in this case, you're saying, like, it interferes with the GABA and the anesthetics don't work the same way, and that is suggestive, but I don't know how conclusive.

[Kelly Wienersmith]

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. In 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.

[Daniel]

Maybe it just interferes. Right. Xenon 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.

[Kelly Wienersmith]

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 to 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.

[Daniel]

And how terrified 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. Cause you can't always predict. Right. How much anesthetic somebody's gonna need.

[Kelly Wienersmith]

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. 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 a, like, atomic level or whatever, you can still form predictions and, you know, do amazing new experiments. Experiments.

[Daniel]

Oh, for sure. There's so many cases where we don't understand the microphysics or it's too complicated for us to model. But we know generally how things behave. And so, absolutely, you don't need to know all the details. I'm just super curious. And. Oh, yeah, 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 gonna, in 10 years, develop new, amazing anesthetics that are better or safer or transcendently wonderful or something? What are people working?

[Kelly Wienersmith]

I didn't get a clear answer on that. They did mention in passing, again how 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, 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.

[Daniel]

Whoa.

[Kelly Wienersmith]

Yeah. So the. The main criteria are that you want the person to be unconscious, not feeling pain, not moving, and making no match memories. So when you're sleeping, one, you move. People sleepwalk sometimes. 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.

[Listener Eric]

Wow.

[Kelly Wienersmith]

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 brainwaves. 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 gonna 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 avoid are staying in the same mode the whole time. And I believe it also just like, creates different sort of electrical patterns altogether. 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 propofol. 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.

[Daniel]

Sleep because he had sleep problems. Right? Okay.

[Kelly Wienersmith]

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, or at least they're not getting done as well. When you're knocked out by something like propofol. 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.

[Daniel]

Oh, my God.

[Kelly Wienersmith]

So it is different than sleep in a way that is very meaningful and important.

[Daniel]

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.

[Kelly Wienersmith]

Yeah, it's incredible. And, 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.

[Daniel]

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.

[Kelly Wienersmith]

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. I've never had someone have to cut into my abdomen, for example. Example. So hurrah for living today.

[Daniel]

All right, well, we hope that journey into the history of anesthesia didn't put you all to sleep or numb your brain.

[Kelly Wienersmith]

It couldn't have. It was fascinating.

[Daniel]

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.

[Kelly Wienersmith]

Sleep tight. And let's end by hearing what Eric about our hour long episode on anesthesia.

[Listener Eric]

Eric, that definitely answered my questions. I went to college in Atlanta, so I think I'm definitely gonna have to be on Team 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.

[Kelly Wienersmith]

Daniel and Kelly's Extraordinary Universe is produced by iHeartradio. We would love to hear from you.

[Daniel]

We really would. We want to know what questions you have about this extraordinary universe.

[Kelly Wienersmith]

We want to know your thoughts on recent shows. Suggestions for future shows. If you contact us we will get back to you.

[Daniel]

We really mean it. We answer every message. Email [e-mail] or you can find us on social media.

[Kelly Wienersmith]

We have accounts on X Instagram, Blue sky and on all of those platforms. You can find us at D and Kuniverse.

[Daniel]

Don't be shy. Write to us.

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