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 von Lewinhook 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 City 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.

Doctor 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 twenty first, eighteen forty six, 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 doctor Robert Liston, who was well known for completing surgeries in thirty seconds or less.

And we know that it took thirty 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 like 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 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 thirty six 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.

Hi.

I'm Daniel.

I'm a particle physicist, and my most terrifying experience with anesthesia was having my ten year old old son go under.

Oh.

Hi, I'm Kelly Waitersmith.

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 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.

Dan, you know 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 resturan 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.

Yeap, 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 to even 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 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 plain episode was my favorite part.

I think I remember ones 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 danieland Kelly dot 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 tailent all works.

I was like, I'm less surprised now, but I'm more terrified.

I guess all right, 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.

As 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 reductionists and 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 did 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 doctor 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.

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?

Why should I start here?

So I got kind of interested in this question and after World War Two, and I promise I won't do like nearly one hundred years of history on this question.

But after World War two 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, because that is a way to show that like you think this is safe, you're invested, blah blah blah.

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 one hundred subjects and the first one is going to be me.

But yeah, you're not supposed to just willing 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 did is not allowed to be considered in future questions, you know, sort of like doctor Mangela'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 a lot across a lot of examples where people have experimented on themselves.

They got the answer they expected, and then they moved forward as so 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 one, but then you need to follow it up with much better, much more broad trials.

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 positions inhaling very 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 are getting the truck.

If I needed to amputate someone's limb, maybe I would want to be not completely present for that process.

But it's like past the pipe there, dude, when you're done.

With this, 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 seventeen ninety nine it was discovered that actuallyitrous oxide does make it so that you don't feel pain.

So Humphrey Davy was he a physics guy?

I don't know, I've 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.

Uh.

He sounds to me like a guy who would sit on a wall and 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 seventeen ninety nine, 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 Cooleridge and doctor Peter Roget who was the guy who compiled with 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 minors safety lamp, and he never pursues this line of reasoning.

So from as early as seventeen ninety nine, 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 seventeen nine nine, before the discovery of nitrous oxide, people would just like Grin and Barrett, 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.

Yeah, So literally you would be you know, you'd take a couple shots of some alcohol.

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 no 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.

Right, maybe it's more of a last ditch option.

Oh god, yeah.

Well, But as a research and 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 two hundred 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 fascinating.

I wonder what they did in ancient Egypt, for example.

You know those guys are pretty advanced, especially in surgery, or are 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.

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 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 Rodgit.

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 eighteen hundreds, 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 sort of surgical implication or plans to 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 physics ether refers to this concept that space is filled with something for like to propagate through, famously disproven by the Michaelson Morley experiment in the late eighteen hundreds.

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 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.

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 heard stopped hurting and you'd laugh a lot more.

And you know that all sounds fantastic.

That sounds great.

Why did you 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 worries 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, all right, we're back.

We were talking about ether parties, which do sound fun, but I would not engage in an ether party because I'm.

A whimp and you're so wholesome, Kelly.

Yeah.

I work 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.

You're a lot of ways.

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 unwined?

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 like you know what.

Kelly's favorite stimulant is the anti anxiety medication.

She's hot.

That's how eye 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 peel.

It helped to 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 doctor 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 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 were sort of sitting in the same room.

So now, like you know, if you've watched Gray'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 guard there and make sure, you know, 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 uh, I wonder if they used to pass around raincoats the way they do it 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.

Uh 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 fundsies.

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.

What 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, yeah, Shakespeare's a couple hundred years before He's like early sixteen hundreds, late fifteen hundreds.

Oh all right, well, and 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 eighteen forty four, 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 he he would be so fun, and.

People would watch this and they're like, let's amputate your leg.

Sure, he he he he.

Well and so uh, 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 off 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, it's 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 here's how much you love him.

You're the best doctor, Cayton.

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 friends 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 we just like sacrifices a healthy molar to science.

Yes, amaz, yeah he does.

I like this dentist.

Yeah, no, me too.

He's willing to 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 Els does this on fifteen other patients, and he decides this is awesome, right, Yeah, So in eighteen forty five, 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 doctor 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 some.

Like emotional nitros oxide.

He needs some of that antidepressants.

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 doctor William Morton and his chemistry teacher, doctor 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 no, no, no, I do that all the time with my classes.

Yeah.

Absolutely, Oh yeah, I don't.

Uh, we're moving on.

So if any administrators that you see or Vara listening, I.

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 put sid a timer and I knocked myself out for eight minutes, and she's.

Like, no, that's not good.

It's not good.

What are you doing.

You're getting drained 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 eighteen forty six and there is a surgeon who is doing a procedure to excize a neck tumor.

At the time, Morton was a second year Harvard medical student, and he gets permission to administer ether well.

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.

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 like comments from a reviewer in the eighteen hundreds, 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 Lethion, which is after the mythological river LETHI.

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.

Would you like to take a trip on the river sticks?

Yeah, no, thank you, I'll pass.

Can you just take this moler out please?

That's one big humbug for that idea.

That's right, amen.

But ether has a super distinct smell, and so Surgeon's 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 gonna 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.

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.

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.

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.

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.

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 eighteen sixty eight, 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 forty eight.

This whole area is like cursed.

I know, it's horrible.

Or maybe it's just the product 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 twelve years and dies at seventy five.

I hope to never be found yelling at gravestone.

Yeah, Like wow, you know, that seems that's pretty high end, Like at the point where your enemy has passed on, I feel like.

You can 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 who's passed and talk to them and connect with them.

And so if Yellen's what you gotta 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 on 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 I don't 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 m M, 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 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 no, I'm glad he lives happily.

Ever after he does well, he dies at sixty two.

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 either.

But 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 nitrosoxide 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 eighteen forty seven 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, 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 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 eighteen fifty three administers chloroform to Queen Victoria while she's giving We're 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 women in childbirth.

Hurrah, Hurrah James and Queen Victoria.

It's amazing how these things are cultural, right have, Like, yeah, one person in one country can turn a whole society in one direction or another to use chloroform and not just 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.

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.

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, right, but I didn't feel any pain.

And he was a ten 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 generalisty 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, oh from the experience of general anesthesia.

Right, yeah, I don't know.

Anyway, Maybe that's more 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 twenty twenty 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 am a lie secular understanding for their action.

This is twenty twenty twenty.

I'm 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 eighteen forty six 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.

We're wading into this controversy.

Yeah, that's right, that's right, but 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 of their achievements, and I'll get along.

I think it would be much nicer to just appreciate the memory of people who took pain away 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 idea or the main idea, And so I ended up talking to doctor Shannon Stem and doctor a Joa Botang Evans.

So, the main mechanism that we think is important here is a neurotransmitter called gabba aminobeic acid or just GABBA.

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 synaps, 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 the threshold, an electrical charge will pass through the neuron, the chemicals will get released into the synaps, 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 networks.

They 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.

Where 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 like 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 sydnaps, 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 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 price.

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 in 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 experiment 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, anesthesia doesn't work the same way in these mice.

So that's pretty good evidence that GABBA is somehow involved in anesthesia.

But in terms of what we know about what these neurons are doing in our brains in response to GABBA, 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 does that?

I've never heard it without 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, saying like it interferes with the gabba 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.

In some cases that works and other cases it doesn't, So there's something we don't understand.

Also, doctor 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.

Xenon can also like kill you because you can breathe it in and it can interfere with you breeding 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 some of the different kinds of anesthetics that we try is making sells 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 anaesiologists who very patiently tried to explain this all to me.

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 because you can't always predict how much anesthetics somebody is 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 a 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.

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 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 ten years develop new amazing anesthetics that are better or safer or transcendently wonderful or something.

I didn't get a clear answer on that.

They did mention in passing again how great we are getting it 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 going under anesthesia different than sleeping or is it the same?

And it's definitely different than sleeping.

So the anesthesiologists I talked to said that it's more like a drug induced reversible coma.

Whoa, yeah.

So the main criteria or 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 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.

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 doctor 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 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 sleep.

Because he has 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, 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.

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.

And you know, despite the fact that we don't really stand this at a mechanistic level, I am still on team anesthesia.

I would not want to live and 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, Yeah, anesthesia opened up much longer, much more complicated surgeries.

And it has, uh, i'd say, really changed our lives in a lot of great ways.

Yeah, and it's so recent right until Yeah, just a couple hundred years ago, surgery was horrible suffering.

M M.

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

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

Your brain 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 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 day.

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