[RADIOLAB INTRO]

JAD ABUMRAD: Batting first, producer Tim Howard.

TIM HOWARD: Cool. Wait, I'm just gonna get my level here. Da da bop be doo. It is such a beautiful day.

PATRICK PURDON: It's beautiful. I think it's got to be, like, 75 degrees out or something. Sunny.

TIM: This is Patrick Purdon. He's a professor in anesthesia at Harvard Medical School, and works at Mass General Hospital.

TIM: You want to just tell me where we are?

PATRICK PURDON: We're standing right now in front of the Bulfinch Building, which ...

TIM: And I went up to talk to him because in that building ...

PATRICK PURDON: Is ...

TIM: This is the one with the Ether Dome?

PATRICK PURDON: Ether Dome is inside this building.

TIM: ... is the story of the day that you could say humanity emerged from the Dark Ages.

JAD: [laughs]

TIM: Oh, you laugh now. Just wait.

PATRICK PURDON: Okay, here we go. It's on the fourth floor. It's on the fourth floor of this building.

TIM: We headed in. Up three flights of stairs into this room.

TIM: What a cool room! Oh, my God! It's just this, like—how would you describe it?

PATRICK PURDON: It's like a mini-amphitheater, right?

TIM: It's also got this awesome dome.

TIM: It's this beautiful, domed room with light streaming down from above.

TIM: [makes trilling noise] Like, the acoustics in here are crazy. It must have been terrifying though, if you actually heard somebody screaming.

PATRICK PURDON: I mean, it's so resonant in here, the screams would have been deafening, and absolutely would have been terrifying.

ROBERT KRULWICH: What is this place?

TIM: Well, this was an operating room.

JAD: Oh!

TIM: And back in the 1800s, when this room was really in use ...

JULIE FENSTER: Being in an operation was so painful, it was often permanently damaging to a patient's emotional state.

TIM: This is Julie.

JULIE FENSTER: I'm Julie Fenster. I write about American history.

TIM: She wrote a book called Ether Day, which goes into a lot of detail about the dark, dark days of surgery in the early 1800s. Back then, during surgery there were no painkillers, and patients were awake. Probably more awake than they'd ever been in their whole lives.

JULIE FENSTER: Some of the patients remembered the sound of their limb dropping to the ground, or the saw going through their sinew and bones. The smell of their own body being cut into. Usually, a surgeon would employ six burly men to hold a patient down. And instead of having an operation, some people committed suicide before they would face going into an operating room, which were usually located on the top floor of a hospital, in part because the hospital really didn't do itself a lot of good to have the screams heard by passers-by.

TIM: This is such a cool room.

PATRICK PURDON: Here we are at the top of the Ether Dome.

TIM: But then everything changes. October 16, 1846. It's a Friday morning.

TIM: I assume the room is full?

PATRICK PURDON: The room is absolutely full.

JULIE FENSTER: The students were all lined up to watch.

TIM: Crowded in the bleachers because they had heard something big was gonna go down. And right there in the middle of the room is ...

JULIE FENSTER: The most esteemed surgeon in America, Dr. John Warren.

TIM: About to do an operation. He brought in a patient who needed a tumor taken out of his neck, and he was just about to slice into the guy ...

PATRICK PURDON: Just about to start the surgery ...

TIM: When this mustachioed fellow bursts in. A dentist.

JULIE FENSTER: William T. G. Morton.

TIM: And he basically said to Warren something that must have sounded completely nuts. "I can erase that man's pain." He didn't actually use those words. He actually had an appointment with Warren. But according to Julie, he did have a bag.

JULIE FENSTER: He had a bag filled with gas.

TIM: A gas called ether.

JULIE FENSTER: And Dr. Warren, who had the scalpel raised ...

TIM: He puts it down.

JULIE FENSTER: ... stands aside and says with great sarcasm ...

PATRICK PURDON: "Well sir, your patient is ready."

JAD: Wait a second. Has he ever tested this?

TIM: He claimed to have tried it out on some dental patients and ...

JULIE FENSTER: On his dog, on himself and on his goldfish.

JAD: Nice.

TIM: So Morton gets to work.

PATRICK PURDON: Morton sets up his gear, fills up the inhaler ...

TIM: Puts it up to the guy's face.

PATRICK PURDON: And actually, because the valve system had just been constructed and he hadn't tested it, he actually literally had to manually operate the valves with every inhale and exhale of the patient. So he administers the ether using this inhaler. After about three or four minutes, the patient becomes unconscious. And just at that moment, Morton turns to Warren and says ...

JULIE FENSTER: "Your patient, sir."

TIM: Dr. Warren brings the scalpel down to the patient's neck and cuts. And really, for the first time in that room, you could hear the scalpel, you could hear the breathing.

JULIE FENSTER: The silence was far more deafening than all the screams that had ever been heard in that operating theater. No squirming, no moving, no bulging eyes, no clenched fists.

TIM: It must have felt like a miracle.

JULIE FENSTER: This—the news of the operation went around the world as fast as anything. News of, you know, war or peace didn't travel faster than this. By the end of the year, doctors in Europe were using surgical anesthetics.

TIM: In basically the blink of an eye, the most painful, horrible experience possibly imaginable became routine, even forgettable.

JAD: But also deeply peculiar, as was made clear to us when we talked a while back with one of our regulars.

ROBERT: Carl Zimmer.

CARL ZIMMER: Well, my wife and I, we were watching this movie one night. It was called Birth, starring Nicole Kidman.

JAD: Oh, did you like it?

CARL ZIMMER: I hated it.

JAD: No! It's one of my favorites.

CARL ZIMMER: Well, okay. I'm sitting there and I'm hating the movie.

JAD: You're hating this movie?

CARL ZIMMER: Well, I'm just wondering, like, why am I reacting so negatively to this movie? I'm just in such a bad mood. I'm feeling lousy, and I think it's the movie. And I stand up and I say, "Oh, wait a minute. My abdomen is in incredible pain."

JAD: Oh, so it's not the movie.

CARL ZIMMER: It's not the movie, it's me.

JAD: Appendix about to burst.

CARL ZIMMER: We go to the hospital, and maybe 4:00 in the morning, 5:00 in the morning, they're prepping me for surgery. They, you know, put an IV in me and then they're like, "Okay, now we're gonna be putting in the anesthetic, you know? So just relax and this will be taking effect."

JAD: But he says it didn't seem to be working.

CARL ZIMMER: So I start thinking about what they're going to be doing to me in half an hour. They're gonna, like, take these knives and they're gonna cut me open. They're gonna rip my intestines apart. They're gonna pull off this inflamed appendix. They're gonna sew up the intestines. They're gonna zip everything back up, and all this is gonna happen supposedly without me being aware of it. And I'm not having any part of it. [laughs] I just said—I just was, like, lying there saying, "I don't think this is working. I'm not feeling anything. You're gonna have to do something more. I just want you to know that I'm not [fingers snap]" And then I was in another room and there was no one else there. Where did they all go?

JAD: Huh.

CARL ZIMMER: Like, they had all left. And then—and then it occurred to me, like, "No. Oh. Oh! The whole surgery's already happened."

JAD: Wow, that is weird!

ROBERT: I've—it's happened to me. It's as if they spliced time, take the time that you were in and the time that you are in subsequently, and the middle is totally missing. No experience whatsoever.

CARL ZIMMER: It's not like sleep.

ROBERT: No.

CARL ZIMMER: There was no like, "Oh, I'm getting sleepy." I was arguing with my doctors that they didn't know how to do their job, and the next thing I'm in a hospital room with my appendix out and it's 10 hours later.

JAD: It sort of implies that it's like a switch.

CARL ZIMMER: It is, and that's what happens. I mean, when you raise the level of anesthesia in someone—and they've done studies on this—it isn't a gentle gradation down. You just—you raise it up, you raise it up and then foom! You are into this other state.

ROBERT: Do—do people who do this for a living know exactly why this happens?

CARL ZIMMER: You'd think that something that's been around since 1846 would be hammered out solid, but it's still almost a philosophical kind of mystery.

ROBERT: There's a term for this in physics. It's called a black box.

JAD: It refers to a system where you can see what goes in, you can see that something different comes out.

ROBERT: And you wonder, like, what happened there in the middle?

JAD: But you can't see it.

ROBERT: Yeah.

JAD: It's a mystery.

ROBERT: It's black and it's closed up. Therefore the box.

JAD: I mean, it might not literally be a box. But today we have three different attempts ...

ROBERT: ... to open three very different black boxes.

JAD: Starting with the box that's in front of us now. That gap that Carl talked about where you go [snaps fingers] boom!

ROBERT: You're gone.

JAD: And then [snaps fingers] suddenly you're back. What happens in that gap?

TIM: That's what's crazy. It's been almost 170 years since William Morton did his thing in front of those med students, and we've moved way beyond ether.

PATRICK PURDON: So here we got propofol. We got sevoflurane, dexmedetomidine, ketamine.

TIM: We've got all these new drugs, but we still don't know exactly how they work. Which for Patrick is a very practical problem.

PATRICK PURDON: It's very difficult actually to figure out when people, you know, aren't conscious, because they can always be internally conscious to some degree, right?

TIM: And in the 1950s and '60s he says, this became a real issue, because doctors started giving patients ...

PATRICK PURDON: Neuromuscular blocking agents.

TIM: That would paralyze their muscles during surgery so they wouldn't flop around, which is a good thing. But then you'd have these situations once in a blue moon where a patient would wake up in the middle of surgery ...

PATRICK PURDON: Literally trapped, unable to move.

TIM: Eyes closed, totally still.

PATRICK PURDON: You know, fully awake, but no one would be able to perceive it because they couldn't move.

TIM: And that's the nightmare that, you know, may even be worse than having six strong men hold you down.

JAD: Oof. Yeah, we don't have to dwell on that.

TIM: Well, I actually did find a bunch of these stories.

JAD: I don't want to hear them.

TIM: No, they're great. I mean, they're—they're—they're amazing. But, all right.

ROBERT: I'd like to hear about it.

JAD: No!

ROBERT: I'm just saying.

TIM: Here, I'll just play you one.

JAD: No! I— no!

TIM: All right, all right, all right. You are gonna regret it, but—well anyway, the larger point is that if you can't understand how and why anesthesia works, then you're not gonna be able to explain why every so often it just doesn't work.

JAD: Oh, really? How often is every so often?

TIM: I've heard different numbers. Anywhere between 1 in 10,000 to much more often, like 1 in 1,000.

JAD: Wow!

TIM: But luckily ...

PATRICK PURDON: Let's take a look at these brain signals.

TIM: In the last few decades, scientists have begun to shine a little pin light into this black box. And Patrick and his team in particular, have found something pretty cool.

PATRICK PURDON: This experiment that we did in the, I guess, late 2000s.

TIM: A couple years ago, they wanted to know what happens in the brain right when that—foom!—switch flips. So they got a bunch of volunteers ...

PATRICK PURDON: Healthy volunteers who ...

TIM: They hooked them up to an IV and started to very, very slowly give them propofol.

PATRICK PURDON: Slowly administer the drug ...

TIM: Which is a big anesthetic. And as they did, they told the subjects to click a button every time they heard a sound or a word ...

PATRICK PURDON: Chair. Library.

TIM: ... that they recognized.

PATRICK PURDON: Submarine. You know, something like that. In addition, we had the subject's name, too. Tim. Patrick.

TIM: So the subjects would just sit there and listen and click.

PATRICK PURDON: Chair. Library.

TIM: On and on.

PATRICK PURDON: Patrick.

TIM: And every 15 minutes, they gave them a little bit more propofol.

PATRICK PURDON: Submarine. Tim.

TIM: Until eventually ...

PATRICK PURDON: They just stopped responding altogether.

TIM: They were just out cold. Now throughout this whole time, Patrick and his team were measuring the brain waves of the subjects. That's the key. And he says what they saw right at the moment that that switch flipped ...

PATRICK PURDON: Right at the moment of loss of consciousness, there was just one really, really clear motif that appeared.

TIM: They saw this wave of electricity sweeping across the brain.

PATRICK PURDON: This really low frequency oscillation, about one cycle per second or less. And in addition to that, there was this higher frequency piece—an alpha wave that appeared at the front of the head at that loss of consciousness moment.

JAD: So when people went under, their brains just started to ring like a bell?

TIM: Basically.

JAD: And why would those—what are those waves doing, exactly?

TIM: It seems like those ways might be imposing a kind of deadly order on the brain. And this is the thing that's very counterintuitive. You think that consciousness is order and synchrony, but it turns out that it's kind of the opposite, that consciousness is actually chaotic and noisy. It's all of those different parts of the brain, you know, facial recognition, touch, sound, language, engaged in this crazily complicated, multi-layered conversation.

CARL ZIMMER: You know, it's one person talking, the other one talking back.

TIM: This is Carl Zimmer again, and he says one of the hallmarks of the conscious brain is that you see a—a kind of conversational logic. A back and forth between the different parts.

JAD: Yeah. My turn, your turn, my turn, your turn.

CARL ZIMMER: The things you're seeing create signals in the back of your head. They go to the front of your head. Back again. Forward and back and forward and back and forward and back and forward and back. And you can use this eavesdropping to calculate how connected the brain is. What they call connectivity. And when you're awake, you have a lot of connectivity. When you're dreaming, you also have a lot of connectivity. And then if someone gives you anesthesia—foop! like, in a matter of a second your connectivity just collapses.

JAD: Oh, maybe that's what happened to you. It just cut—your connectivity got cut.

CARL ZIMMER: It did.

TIM: And here is the weird part.

CARL ZIMMER: Scientists will, like, play a sound to somebody who's under with anesthesia, and they can see that actually the part of the brain that processes sound, the auditory cortex, is active.

JAD: Oh!

CARL ZIMMER: It takes in the sound. So your brain is hearing sounds ...

JAD: That's spooky!

CARL ZIMMER: Yeah.

TIM: So what could be happening is that when you're under anesthesia, all the different parts of your brain to some degree, they could be awake.

CARL ZIMMER: It's not—not your brain is just stopping.

TIM: No. All those parts of the brain are still talking, they're just not talking to each other ...

CARL ZIMMER: ... very well anymore.

TIM: And that somehow knocks you out.

JAD: So lots of chit-chat amongst the different parts of my brain make me conscious, and not so much chit-chat equals unconsciousness.

TIM: Yeah, that's the idea.

JAD: And how do the slow waves relate to that?

TIM: Well, Patrick thinks of it in—sort of in baseball terms.

PATRICK PURDON: Right. So actually, I was at a Red Sox game the other day. It was the last one that they had with the—with the Yankees at Fenway Park this year. And at some point the wave started. So some part of the stadium decided to go into the wave, and here you go, the wave's coming around and coming around and you're watching it, and it keeps coming around and coming around. And, you know, after a while it gets really tiresome. Because you're sitting there and you're just like, "Okay. I've gotta wait for the wave to come. Okay, here it is again. Okay, stand up, raise our arms." You sit back down, and—and just a moment later like, "Oh, my God. I gotta stand up again." And—and you're waiting. "Oh dude, it's back again." And—and the thing is that when the wave is going on in the stadium, you can't really carry on a normal conversation. You can't have a normal interaction. You may not even be able to have a normal thought because the thing is just coming by every couple seconds to interrupt you. That is sort of the rationale for how these oscillations disrupt brain activity.

JAD: I dig the analogy, but I'm not quite following.

TIM: It helps to—to zoom in on the brain and look at a smaller number of neurons.

JAD: Okay.

TIM: Which is what he did.

PATRICK PURDON: Now check this out. We conducted this study where we measured brain activity in individual neurons.

TIM: They got some patients, planted these tiny little electrodes deep into their brains so they could hear the individual neurons.

PATRICK PURDON: So let's imagine that we zoom in to, like, tens to hundreds of neurons firing. And ...

TIM: He says when they give that patient propofol, an anesthetic ...

PATRICK PURDON: What we notice is that right at the point of loss of consciousness ...

TIM: Sure enough, they see those big slow waves sweeping through. And just like in Fenway when the wave hits you, you have to stop your conversation. But what that wave is really doing is it's only allowing each little cluster of neurons to talk once in a while.

PATRICK PURDON: They can only fire at a particular moment in this slow oscillation.

TIM: Like, you know how the wave goes up and down and up and down, or round and round and round if you're in Fenway. It's only at this moment, say, that one group gets to talk. The problem is his buddy, he can only talk at this moment. And the neurons next door, they can only talk at this moment. The next group, same deal. Everybody gets a turn to talk, but they can't talk to each other because they're on slightly different schedules. When they're talking, the others can't listen. So there's still a lot of talking going on, but consciousness seems to be the brain talking and listening to itself. So when that slow wave rolls around ...

PATRICK PURDON: The neurons can't all fire at the same time and talk to one another. And in that state, it would be impossible to be conscious.

TIM: Is it—it might be early to say, but does it feel kind of like you cracked the code?

PATRICK PURDON: Well, I think we are in the process of cracking the code for anesthesia. You don't ever want to get, you know, too far out on a limb. But honestly, I mean I feel if we can educate people about these rhythms, you know, I'd be willing to say it. Sure, I think we have. I mean, I think this is gonna be huge. I'm not gonna lie to you. I think this is just gonna be absolutely huge. Yeah, I'll take the bait on that, sure. [laughs]

JAD: Crack the code? Really? That's—that's a little bold.

TIM: Well, what it means to Patrick is that in very practical terms, he can now peek into that black box of the brain.

EMERY BROWN: Okay, here I am. I'm wearing my scrubs.

TIM: For example, Patrick and his colleague, Emery Brown ...

EMERY BROWN: I'm an anesthesiologist here at Mass General.

TIM: ... they let me watch a couple surgeries. And I met a woman named Doris.

TIM: Good morning.

DORIS: Morning.

TIM: What kind of surgery are you having today?

DORIS: I'm having the repairing of a hernia.

TIM: It's a surgery that, you know, 170 years ago would have been unthinkable. But here she is.

DORIS: I feel comfortable.

TIM: Not too worried.

PATRICK PURDON: So they're about to give her the first anesthetic.

TIM: First anesthetic? Propofol?

PATRICK PURDON: That's right. Yep.

TIM: And as she starts to go under ...

EMERY BROWN: Deep breath Doris. In and out. Don't stop, Doris.

PATRICK PURDON: So I'm gonna just switch over the spectrogram display and see what it shows us.

EMERY BROWN: Deep breath, Doris.

TIM: On one of these monitors ...

PATRICK PURDON: Oh, look at that. Did you see that change?

TIM: Yeah.

TIM: It's a color display. You can actually see it happen.

PATRICK PURDON: You can see the slow waves, right? Now—now she's got some slow oscillation.

TIM: If you imagine the screen as, like, this field of blues and yellows and greens, suddenly these bands of red just extend right along the bottom. And considering that for the last 160 years, anytime somebody like Doris has been put on a table and cut open, the doctors basically couldn't be sure what was going on in their head. Are they awake? Are they okay? And so with that in mind, being there in the operating room and seeing that band of red appear on the screen and hearing Emery Brown declare without hesitation ...

EMERY BROWN: This patient is unconscious.

TIM: ... it's kind of cool.

TIM: And you say that with what percent confidence?

EMERY BROWN: Oh, 99.999999999.

[fingers snap]

TIM: And then I was in another room.

 

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