May 5, 2021
Transcript
[RADIOLAB INTRO]
JAD ABUMRAD: Hey, this is Radiolab. I'm Jad Abumrad. Today, some simple science. Two stories of incredibly simple scientific discoveries, one from modern times and the other right out of the past. To start, we're gonna play a show that Molly Webster and Robert Krulwich did a few years back. At the time, this was 2016, was breaking news. But it also includes some updates that came out in about 2020. So I'm gonna let them take it from here.
ROBERT KRULWICH: Hi, I'm Robert Krulwich.
MOLLY WEBSTER: I'm Molly Webster.
ROBERT: This is Radiolab and today ...
MOLLY: We've got breaking news, Robert Krulwich.
ROBERT: Well, great! This is something we've never done before.
MOLLY: Never done before.
ROBERT: Well, does anybody know about this yet?
MOLLY: Well, it is a new bit of research. It's being published today.
ROBERT: Uh-huh. What's this thing about?
MOLLY WEBSTER: This is a discovery about Alzheimer's disease.
ROBERT: Uh-huh.
MOLLY: Which I think at this point is something that affects basically every family.
ROBERT: Affected my family, yeah.
MOLLY: Yeah. And this is a discovery that is not a cure, but it's basically about looking at the brain, which is one of the most complicated things in the universe, I think, and poking at it in this super simple way, and getting this bizarre result.
LI-HUEI TSAI: Hello.
MOLLY: Hello, hello?
LI-HUEI TSAI: Hi, Molly.
MOLLY: Hi.
LI-HUEI TSAI: Hi, how are you?
MOLLY: All right, so last May I was talking to some folks over at the Brain Institute at MIT, and while I was on the phone with them, they started telling me about some research that hadn't been published yet, so it was all very hush hush. It was pretty cool, though. We ended up deciding to sign a non-disclosure agreement, and it was based on the work of this woman Li-Huei Tsai.
LI-HUEI TSAI: Li-Huei Tsai. I'm a professor and a director of the Picower Institute for Learning and Memory at MIT.
MOLLY: Holy crap. You're the director. How do you have time to do all that?
LI-HUEI TSAI: I know! That's a good question. [laughs]
MOLLY: She is like a badass, is what she is.
LI-HUEI TSAI: But this is the piece of work I'm very proud of. So historically, people work on Alzheimer's really focus a lot on ...
MOLLY: So I would say generally, when you talk to researchers about Alzheimer's disease, they either focus on ...
LI-HUEI TSAI: ... on individual genetic factors,
MOLLY: ... the genetics of the disease, so the genes that predispose you, maybe to Alzheimer's.
LI-HUEI TSAI: Or ...
MOLLY: The brain chemistry, and how Alzheimer's affects the chemicals of the brain.
LI-HUEI TSAI: Molecular pathological features.
MOLLY: But in my conversation with Li-Huei, she was talking about something totally different.
LI-HUEI TSAI: We sort of look at it from a different angle.
MOLLY: Her work all centers around something called ...
LI-HUEI TSAI: The gamma frequency.
ROBERT: The gamma frequency?
MOLLY: Mm-hmm.
LI-HUEI TSAI: Gamma.
MOLLY: And what is—I'm like, it feels like something from Battlestar Galactica.
LI-HUEI TSAI: [laughs]
MOLLY: So I don't think it's that.
LI-HUEI TSAI: So, this gamma ...
MOLLY: You could think of it as a particular beat in your brain.
ROBERT: A beat in the brain.
MOLLY: Yeah.
LI-HUEI TSAI: Yeah.
ROBERT: Which means what, exactly?
MOLLY: Well, just to oversimplify one of the most complicated things in the known universe ...
ROBERT: [laughs] Okay, please do.
MOLLY: You've got your brain. It's full of neurons, which are a certain type of brain cell.
LI-HUEI TSAI: We have billions of neurons in the brain.
MOLLY: They have these long tentacles that are reaching out towards other neurons.
LI-HUEI TSAI: And for the brain to function, neurons have to communicate with each other to process information.
MOLLY: And the way they do that is they fire.
LI-HUEI TSAI: Yes.
MOLLY: An electrical signal will go through them and it'll, like, zap another neuron, and it'll turn it on. And then an electrical signal will go through it and it'll zap another neuron, and it'll turn it on. But the cool thing is is that when your brain is doing things like making you move, or write a poem, or think great thoughts, groups of neurons ...
LI-HUEI TSAI: Fire in sync.
MOLLY: All together on the same beat. And there's a bunch of different beats that happen in the brain. Some of them are slow, like one beat per second, and that's when you're sleeping. If you're beating around 10 beats per second, like, maybe you're sitting next to a campfire in an Adirondack chair. Or on, like, the totally other end of the spectrum, like, some neurons fire at 600 beats per second.
ROBERT: What are they doing?
MOLLY: That I have no idea.
ROBERT: And all this is going on in your head simultaneously?
MOLLY: Yeah, yeah, yeah. No, that's the cool thing is that when all of these beats in your brain come together, that's when you're able to process the world and understand it as it exists as human beings.
ROBERT: Huh.
MOLLY: But getting back to our story, when your brain is doing something really tricky that requires super focused ...
LI-HUEI TSAI: Attention, working memory, and so on.
MOLLY: You're, like, trying to find your way home from the subway station, or if you're in a new city, navigate around it, there's a certain beat that sort of rises above them all, and that is ...
LI-HUEI TSAI: The so-called gamma frequency.
MOLLY: This range between 30 beats per second all the way up to 100 beats per second.
LI-HUEI TSAI: And this gamma frequency has been considered to be very important for the higher order cognitive function.
MOLLY: And the interesting thing is that when you look at an Alzheimer's brain, what you see is there's actually less gamma happening, or people say the power of gamma is reduced.
LI-HUEI TSAI: Not all the neurons can be recruited to oscillate at the gamma frequency.
MOLLY: It's still there, it's just quieter.
MOLLY: It's like you turn the volume down.
LI-HUEI TSAI: Right.
ROBERT: All right, so just to briefly sum up here, what we've got is a rhythm, which we call gamma, which is used when we have complicated or higher thoughts in the brain, which when you've got Alzheimer's, kind of gets saggy, or tired. It vanishes.
MOLLY: Yeah. Yeah, totally, and of course, obviously in an Alzheimer's brain, there's a lot going on, and this is just one of the things, right? You've got the plaques that build up around the neurons.
ROBERT: The stuff that gucks up your brain, and makes it hard to think.
MOLLY: Yeah, yeah, yeah. Totally. It's like cobwebs in the brain. And then the connections between neurons gets all muddied, and immune cells get messed up. But Li-Huei Tsai was like, "Forget all that. What would happen if I just bring the gamma back?"
LI-HUEI TSAI: Yeah. We decided to just manipulate gamma oscillations.
ROBERT: And how do you—how do you do that?
MOLLY: Well ...
MOLLY: [blows into mic] Hello, hello, hello, hello, hello, hello, hello, hello?
MOLLY: ... technology ...
MOLLY: Hi, this is Molly. Hi, hi, hi.
MOLLY: ... technology you can find at the Massachusetts Institute of Technology.
MOLLY: We're walking into the Picower Institute.
MOLLY: It's a ...
MOLLY: Wow!
MOLLY: ... big shiny glass building.
LI-HUEI TSAI: Molly, hi! Nice to meet you.
MOLLY: Eventually, Li-Huei Tsai came striding into her office to meet me.
LI-HUEI TSAI: My understanding is that you want to see some of the experimental setup.
MOLLY: And so Li-Huei led me down the hall to this tiny room.
LI-HUEI TSAI: So ...
MOLLY: So here's what they did: they get some mice.
LI-HUEI TSAI: We started off with a mouse model.
MOLLY: Mice that have an early stage of Alzheimer's disease.
LI-HUEI TSAI: With multiple notable defects.
ROBERT: Do they have the gunky plaque stuff in them yet, or is that later?
MOLLY: No, but they do have ...
LI-HUEI TSAI: Elevated levels of beta-amyloid peptides.
MOLLY: Which is this protein that forms the plaques, so it's like basically pre-plaque gunk. But the important thing to Li-Huei Tsai and her team is that they have less gamma going on in their brains. If you remember, the whole plan here is to bring the gamma back.
LI-HUEI TSAI: Yes.
MOLLY: So to do that, they get what might be the world's tiniest drill, and they drill a small hole into the skull of the mouse, and then they take a really thin fiber-optic cable, they slide it through the hole into the brain. And then they get this laser of blue light ...
LI-HUEI TSAI: To flicker.
MOLLY: At 40 beats per second.
LI-HUEI TSAI: Gamma frequency.
MOLLY: And they turn that on, and the light travels down the fiber-optic cable, deep down into the brain, to this group of cells that they've modified ...
LI-HUEI TSAI: In the hippocampus.
MOLLY: ... to be sensitive to light. So when this pulsing light hit these cells, they actually began to fire at 40 beats per second.
LI-HUEI TSAI: At gamma frequency.
MOLLY: And they would keep these cells firing at gamma ...
LI-HUEI TSAI: For one hour.
MOLLY: Firing and firing and firing and firing and firing.
LI-HUEI TSAI: And then after one hour ...
MOLLY: They turn off the light, and then eventually they started looking at the brains of these mice, trying to figure out if anything was different after the light flashed. And they see ...
LI-HUEI TSAI: To our much surprise ...
MOLLY: They were not expecting this at all.
LI-HUEI TSAI: We found ...
MOLLY: After they shot this pulsing light into the brain, there was suddenly nearly half as much of that soon-to-be nasty plaque gunk stuff that was filling up their hippocampus.
ROBERT: A half of the ...
MOLLY: Yeah.
ROBERT: Half?
MOLLY: Half of the stuff was just swept away.
LI-HUEI TSAI: Yes. 40 to 50 percent reduction of beta amyloid.
MOLLY: That just seems crazy! [laughs]
LI-HUEI TSAI: This is crazy! I mean, we were just so surprised.
ROBERT: Do they know why the flood of light would ...
MOLLY: Yeah, yeah. So ...
LI-HUEI TSAI: Turn out ...
MOLLY: ... the pulsing light somehow triggered the brain's cleanup crew.
LI-HUEI TSAI: Microglia.
MOLLY: These cells in the brain that are called microglia.
LI-HUEI TSAI: You can say they're the janitors of the brain.
MOLLY: And in a normal brain, these janitor cells usually gobble up the gunk.
LI-HUEI TSAI: But in Alzheimer disease, it's known that microglia, they don't sort of function normally anymore.
MOLLY: It's like these janitors just sort of ...
LI-HUEI TSAI: Stop cleaning up.
MOLLY: And go on strike.
ANTHONY MARTORELL: There we go. Okay. Cool.
MOLLY: Okay, so we're looking at a screen that's now flat. It's not ...
MOLLY: When I was at MIT, one of Li-Huei's graduate students ...
ANTHONY MARTORELL: My name is Anthony Martorell. Second year.
MOLLY: ... was showing me side-by-side comparisons of these mice brains on a screen.
ANTHONY MARTORELL: Can you guess what that is?
MOLLY: Wait, wait. Which part?
ANTHONY MARTORELL: The green thing?
MOLLY: Microglia!
ANTHONY MARTORELL: Microglia, yeah. [laughs]
MOLLY: And you see ...
LI-HUEI TSAI: After one hour of gamma ...
MOLLY: Wow! So yeah, that part ...
LI-HUEI TSAI: ... the microglia, the cell, seems a lot bigger.
MOLLY: Can clearly see these round bodies.
LI-HUEI TSAI: Yeah.
MOLLY: Yep.
LI-HUEI TSAI: Yeah, and also, the belly seems to have more amyloid.
MOLLY: Oh, like they're doing more eating.
LI-HUEI TSAI: Yes, they go back to eat more amyloid again.
MOLLY: It's like somehow making the neurons fire turned on the sanitation system in the brain.
LI-HUEI TSAI: But—but the most wild result ...
MOLLY: Wait, there's more wild?
LI-HUEI TSAI: Oh my God! You've gotta hear this.
MOLLY: [laughs] Okay.
LI-HUEI TSAI: Because what I'm about to tell you, you may say, "No, I don't believe it. It's science fiction."
MOLLY: Okay, so one of the things Li-Huei and her team were starting to think was that drilling and fiber-optic cable ...
LI-HUEI TSAI: Is very invasive, right?
MOLLY: You'd never be able to do that on a human.
LI-HUEI TSAI: Exactly. So we started to say ...
MOLLY: "Well, what if we can get the light into the brain in a different way? Like, maybe we could go through the eyes."
ROBERT: So the hole in your head would be your eyes instead of a hole in your head?
MOLLY: Yeah. Yes.
ROBERT: Hmm.
MOLLY: So Li-Huei and her team created what I like to think of as the flicker room.
MOLLY: Wait, is this the room?
LI-HUEI TSAI: This is the room, and ...
MOLLY: Okay.
MOLLY: It turns out, I learned upon my visit, that it is just a storage closet.
MOLLY: You know, you have a—what is this, just a plastic table?
MOLLY: Very DIY.
ANTHONY MARTORELL: Yeah, it's a plastic table you can buy at Target.
MOLLY: There were some plastic shoebox-sized containers lined up on the table for the mice, and then ...
LI-HUEI TSAI: You see the strip?
MOLLY: ... around the edge of the table ...
LI-HUEI TSAI: Basically, surrounding all the cages.
MOLLY: ... are duct-taped strips of LED lights.
ANTHONY MARTORELL: And the reason why we use LEDs is because a regular light bulb, it can't flash fast enough.
MOLLY: And so the idea is: what if we just put the mice in this room, and just let the light flicker at 40 beats per second?
LI-HUEI TSAI: So you want to show Molly? Like, turn this on?
MOLLY: Yeah!
MOLLY: And so we turn off the overhead light in the room so it's very black, and then ...
MOLLY: Oh, wow!
MOLLY: ... the room was now glowing with this white LED light.
ANTHONY MARTORELL: Okay, so the light is turning on and off 40 times a second.
MOLLY: So you don't see anything going, like, on or off. It just looks like something's on, but it kind of feels like my eye is twitching.
LI-HUEI TSAI: Exactly.
MOLLY: And so it's blurring the light a little.
LI-HUEI TSAI: Correct.
MOLLY: Just on the edges, though.
LI-HUEI TSAI: Yeah, just on the edges.
MOLLY: And so they put mice in this room for an hour, and just let them kind of bathe—bathe in this glow.
LI-HUEI TSAI: And guess what?
MOLLY: What?
LI-HUEI TSAI: We look at the amyloid beta levels in the visual cortex, and we found there is a 50 percent reduction.
MOLLY: [gasps] 50 percent?
LI-HUEI TSAI: 50 percent reduction.
MOLLY: Just from shining light in their eyeballs?
LI-HUEI TSAI: Yes!
ROBERT: Wait a second, they didn't do any drilling in their skulls or anything?
MOLLY: No! No, they didn't drill. They didn't tweak the mouses' brain cells to be sensitive to light. This is just ...
ROBERT: They just filled the room with occasional LEDs flashing at a particular frequency?
MOLLY: For an hour.
LI-HUEI TSAI: Now do you see? [laughs] Are you going to tell me, "I don't believe it. It's science fiction"?
MOLLY: And they followed this study up with another study which was done in the same way, so the same flicker room, light through the eyeballs. Only this time, they put the mice in there for one hour a day for seven days, and they took mice that had full-blown Alzheimer's. So this is cognitive decline, they're forgetting things, and they've got hardened plaques in their brain. And they see the same thing: nearly half of the stuff was cleared away.
ROBERT: Wow!
MOLLY: Half!
ROBERT: Wow!
LI-HUEI TSAI: It's just flickering light in front of the mice.
MOLLY: I mean, that's the shocking thing. The thing I didn't understand after talking to you about your study was, I was like, "Why hasn't everyone done this before?" Like, why didn't everyone go, "We should just shine light through eyes?"
LI-HUEI TSAI: Well, you know, that's really the most unexpected and exciting aspect of our study, which is something this simple, yet it has never been done before.
MOLLY: One of the things—one of the caveats here is that if you don't do the flicker-light room every 24 hours, the level of gunk in the brain starts going back up again. And so now they're trying to figure out how they can keep those levels down—maybe even for good.
MOLLY: So when we originally reported this in 2016, it was all breaking news, it was off the record. Since then, Li-Huei Tsai has gone on the record, and she and her team have expanded their experiments to include sound. So it's basically the exact same experiments, but with sound at the gamma frequency.
JAD: So wait, do we know what it sounds like?
MOLLY: I have it here.
JAD: Oh!
MOLLY: So I'm gonna hit play. Oh my God, it's kind of a crazy sound! [laughs] I almost don't want to hit play. Okay. Three, two, one.
[buzzing sound]
JAD: Oh, God!
MOLLY: Yeah.
JAD: Whoa.
MOLLY: Yeah.
JAD: It's like a little insect boring into my brain, and there's like a sub-bass in there that's making my stomach like—ugh!
MOLLY: Right? I—the first time I heard it, I ripped my headphones off my head, and then I—then really converted and found it super soothing.
JAD: I'm not there yet. [laughs]
MOLLY: Okay. I think we should probably also do the caveat of, like, there could be some way in which this comes through your headsets in a weird way. It depends on where the speaker is set. Yada, yada, yada. Where this is not the sound in a way that they are playing.
JAD: Yes, totally. And maybe we'd even want to take it a step further and say, "Do not use this sound." [laughs]
MOLLY: Yes, please do not use this sound at home to self treat. They were playing this for mice. And when they were playing it for mice, they were able to see very similar effects as when they did the flashing lights in the flickr room.
ROBERT: If the mouse no longer has quite as much junk in its head, does that mean that it can remember things that had happened to it? It gets mentally more acute?
MOLLY: Yeah. Yeah, that is their big next research. That's what they're ...
ROBERT: So they don't know.
MOLLY: They don't know. That's what they're—that is now the next step. But nobody really understands how plaques and the gunk buildup in the brain relates to memory and cognition, and the dogma in the field is that when you have Alzheimer's, you can't form new memories, and once you lose a memory, it's gone for good.
ROBERT: Huh. Okay.
MOLLY: But there is another group at MIT that is actually sort of challenging that assumption that you can never get a memory back.
DHEERAJ ROY: Because the patient could never tell us, we all assumed the information had to be gone.
ROBERT: Oh, really?
MOLLY: Yeah. And we'll get to them. But first we have to go to a break.
JAD: Hey, Jad here. We are back looking back at Molly Webster's piece from 2016, peppering in some updates as we go. We're gonna keep rolling here with the original for a beat and then we'll get more from 2020 Molly and me in a little bit.
ROBERT: I'm Robert Krulwich.
MOLLY: I'm Molly Webster.
ROBERT: This is Radiolab.
MOLLY: And we're back.
ROBERT: And just before the break, you said that there may be a way to bring a memory back from Alzheimer's disease.
MOLLY: Mm-hmm.
ROBERT: To pull the memory back into place.
MOLLY: Yeah.
DHEERAJ ROY: Why are we so quick to jump to the conclusion that the information was somehow completely gone?
MOLLY: And the person who said that to me is this guy.
DHEERAJ ROY: I'm Dheeraj Roy. I'm a fourth-year graduate student in the Susumu Tonegawa Lab.
MOLLY: Over at the Tonegawa Lab, they were thinking, "What if we could figure out exactly where the memory should be in the brain, and just give that spot a little bit of juice?"
DHEERAJ ROY: Right.
MOLLY: So they took some mice that were just starting to lose their ability to remember things, and they thought, "Okay, let's try to give them a memory."
DHEERAJ ROY: We put them in a box that has a particular smell, some sort of lighting, and some texture on their feet.
MOLLY: A little mouse carpet, or ... [laughs]
DHEERAJ ROY: That's exactly what it is.
MOLLY: Wait, really?
DHEERAJ ROY: Yeah. [laughs]
MOLLY: Okay, mice on carpets. Got it.
MOLLY: The point is the box looks and feels and smells different than any other box they would hang out in.
DHEERAJ ROY: And then we give them a light electrical shock.
MOLLY: And the mice, they just freeze.
DHEERAJ ROY: They don't move at all.
MOLLY: Which is a sign that they're afraid.
DHEERAJ ROY: They hate the box.
MOLLY: And for the rest of the afternoon—which is a very long time in mouse time—they go on hating the box, which means with the carpet and the light and the smell, if you put it back in there, it'll freeze because it remembers the shock.
DHEERAJ ROY: Yes.
MOLLY: But ...
DHEERAJ ROY: A day or a week later ...
MOLLY: When these same mice were put back into the same box ...
DHEERAJ ROY: Instead of being scared of the box, they would just continue investigating as if nothing happened. They could not remember.
MOLLY: So Dheeraj and his team did what Li-Huei did: they got some modified mice, and then they put a little hole in their head. They slid in a fiber-optic cable. They shined some light to trigger the neurons that they think hold this memory. And they were ...
ROBERT: In the fear section.
MOLLY: Near the fear section. So leading on the path to the fear section.
DHEERAJ ROY: So we do this ...
MOLLY: And then ...
DHEERAJ ROY: Put them back into the box.
MOLLY: The box with the particular lighting and smell and carpet.
DHEERAJ ROY: And ask is there any change in their behavior?
MOLLY: Will they act afraid again?
DHEERAJ ROY: Do they show any more memory? And they did. They showed recovered memory.
MOLLY: Wow!
ROBERT: Whoa.
MOLLY: So that's like—bam, that memory's in there.
DHEERAJ ROY: Exactly. Voila, the behavior was back.
ROBERT: You can dig up the memory by shining light in the right place?
MOLLY: Yeah.
DHEERAJ ROY: Mm-hmm.
MOLLY: I was always under the impression that the memories were totally lost.
DHEERAJ ROY: Right. So I think that's not just you. I think that's essentially the entire field, what you described.
MOLLY: Oh, okay. Well, that's good.
DHEERAJ ROY: Just because the patient could never tell us, we all assumed the information had to be gone.
ROBERT: Huh.
MOLLY: So one of the things to say is that Dheraj did tell me that, you know, all the experiments they did are in mice that have early Alzheimer's. The thought is, though, is that once you get to the late stage of the disease, there's enough damage in the brain that you really wouldn't be able to get those memories back.
ROBERT: That might be right, that a memory loss is just loss. But when you have someone in your house and you live with this disease day in and day out, the disease just goes its own way.
MOLLY: Uh-huh.
ROBERT: And it can puzzle you or frighten you or suddenly declare something new that you didn't expect. So for example, my dad had it for about nine, ten years. It was a slow act of disappearing that he did. I mean, the last time my father came to was so far into the disease, he hadn't spoken for a year and a half. He was sitting at the table for the Passover Seder, and there's a song that you sing, and it goes [singing]. So it's just a chorus, and from out of nowhere, this being at the end of the table who I knew was my father, who hadn't spoken in a year and a half or two, and had not spoken coherently for three, suddenly flew into the song, and sang the song full-throatedly at the table, like the reappearance of some last figment of himself. And it was—it was both horrifying and extraordinary. Both.
DHEERAJ ROY: I mean, I think that's—the fact that maybe some information still persists, hopefully someday we could kind of—maybe there's something we could do. But yeah, this is all in my mind at the moment.
LI-HUEI TSAI: As long as we can figure out how to rebuild the pathway to retrieve the memory, then I think there is hope.
MOLLY: And then I want to jump in here with one more part of the sound update, which is that Li-Huei and her team in particular are thinking about it in regard to capturing memories. Because where this research probably gets even, like, more interesting is when you do the light flashing and that sound at the same time.
LI-HUEI TSAI: We eventually just decided why don't we, you know, put the two together and see how the animals respond?
MOLLY: This is becoming like a mice spa.
LI-HUEY TSAI: [laughs]
MOLLY: And when they did that, they saw this gamma beat in the brain, but not just in the auditory cortex or the visual cortex.
LI-HUEY TSAI: Not just in one particular brain region, now we are seeing across different brain regions.
MOLLY: So the hippocampus got involved and the prefrontal cortex got involved. And then there was the neocortex and maybe even the parietal lobes. So there was, like, activity, like, all across the brain.
JAD: Is it a little bit like a whole bunch of clocks coming into sync?
MOLLY: Yeah. Yeah. And imagine thinking it's only gonna affect one clock, but it actually somehow pulls them all into synchrony. Again, they saw the microglia doing their cleanup thing all across the brain, but they also saw almost like a rebuilding of neuronal circuitry. So, like, the synapses between neurons seemed to improve.
LI-HUEI TSAI: Then basically, this repaired the disrupted neurocircuitry, and I think this in turn, can lead to recovery of learning a memory.
MOLLY: Basically, in a way, she's done something very similar to what Dheeraj has done, but with her own light and sound technique, and the memories came back.
JAD: That's so interesting!
LI-HUEI TSAI: And the mice show very impressive improvement to their cognitive ability.
MOLLY: So it's almost like two things happening, which is you're seeing physiological effects in the brain, and then you're seeing the layer on top of that, which is then the memories that live in the physiology are also having some impact.
LI-HUEY TSAI: Yes.
MOLLY: So with all the stuff—super new, so I feel like it's caveat time.
LI-HUEI TSAI: You know, I personally think the most important question is whether humans respond similarly.
MOLLY: I mean, keep in mind that both Dheeraj's study and Li-Huei Tsai's are in mice, not humans.
LI-HUEI TSAI: Right, so I ...
MOLLY: And do you have a thought that why—like, is there a reason that a human neuron might react differently than a mouse?
LI-HUEI TSAI: The thing is, I think, you know, especially in Alzheimer's field, I mean, people got burned a lot.
MOLLY: You know, there's like a 99.6 percent failure rate in moving something that seemed to work in mice to humans in Alzheimer's.
ROBERT: 99.6?
MOLLY: Yeah. Yeah, that was a study that came out in 2012.
ROBERT: That's a horrible number.
LI-HUEI TSAI: So I just gotta be really conservative.
MOLLY: I'll dial it back. I'll dial it back.
LI-HUEI TSAI: You know, what we have in mice, it's just so exciting and so unexpected but, you know, I'm gonna keep my mind open when it comes to humans.
MOLLY: And so we have my final final update, which is that Li-Huei Tsai and her crew have started human trials.
LI-HUEI TSAI: So we indeed managed to get an RB approved for our first very small scale study in early stage Alzheimer's disease subjects.
MOLLY: They're doing a clinical trial with 15 Alzheimer's patients.
JAD: How far into the study are they?
LI-HUEI TSAI: So we have recruited 15 individual people. We basically installed our light and sound device in their home.
MOLLY: Really?
LI-HUEI TSAI: Yeah. So they themselves or their caregiver can turn on the device.
MOLLY: And then they sit there and they get the light flashed in their eyes, and they get the sound flashed at their ears. And they're doing it an hour a day for six to eight months, maybe six to nine months, and they're just collecting data and I guess we're gonna see.
LI-HUEI TSAI: We are talking about living human beings. It's not that we can just take out their brain and see their microglia or all this, but we are evaluating all of the subjects in terms of their cognitive ability, and we also do MRI scan to look at how active their brain activity is.
JAD: And do you have any intel on what they're seeing so far?
MOLLY: Nada. I wish.
LI-HUEI TSAI: I mean, every step of the way, to be quite honest, it's always a surprise. It's like, oh, Gamma can do this and Gamma can do that.
ROBERT: This is the glorious part of all this, this organ of ours, the brain, is so crazily complicated with, like, whatever, 100-trillion connections or whatever it is. There's so much chance there's gonna be a lot of surprise!
MOLLY: Yeah. It's like almost even if it doesn't lead to any treatment in humans or something super concrete, it's like we know this little secret about the brain now, and there's something that feels beautiful in that.
LI-HUEI TSAI: Yeah, I'm actually setting this up for my Christmas tree.
MOLLY: Are you really?
LI-HUEI TSAI: Yes. Yeah, we—I just bought the new LED lights, and they can flicker a different color, with different colors.
MOLLY: Oh, so each individual bulb can travel through colors, but while they're doing that, they're gonna be flickering at 40.
LI-HUEI TSAI: We're gonna have a very therapeutic Christmas. [laughs]
MOLLY: In the Li-Huei Tsai household? This is the tree in your home?
LI-HUEI TSAI: Yes. Yes.
MOLLY: I want to have an eggnog next to that tree.
ROBERT: Yeah.
JAD: Hey. I'm Jad Abumrad.
ROBERT: I'm Robert Krulwich.
JAD: This is Radiolab. And today ...
ROBERT: Well, today it's the story of an ax-wielding nun coming through a window to smack some staphylococcus, and take you back to the future.
JAD: [laughs] Exactly. This story comes ...
ROBERT: Does that make any sense? I don't know.
JAD: Well, it will.
ROBERT: Okay.
JAD: It will. This story comes in two parts, both from our producer Latif Nasser. And here's part one.
LATIF: So the way the story goes, it starts in 1928.
MARYN MCKENNA: 1928. Alexander Fleming, the story goes—who knows if it's apocryphal or not—is growing staph, staphylococcus, in his lab.
LATIF: That's Maryn McKenna. She's a science writer. And staph is a bacterium.
MARYN MCKENNA: It lives on our skin, and it especially likes parts of the body that are warm and damp.
LATIF: So it likes to be just up our noses, or ...
MARYN MCKENNA: On our genitals, or in our armpits. Places like that.
LATIF: And generally, it's no big deal. Doesn't really do us any harm. But if it gets into a scratch or a cut and makes its way inside our bodies ...
MARYN MCKENNA: Staph goes from being this benign companion to being potentially deadly.
LATIF: Anyway, London, 1928.
MARYN MCKENNA: Fleming is growing staph in his lab.
LATIF: In these little Petri dishes. And he was a slob, basically.
ROBERT: [laughs]
LATIF: And he goes on a vacation, leaves his Petri dishes covered in bacteria just around. Leaves his window open.
MARYN MCKENNA: And something blows across his lab plates.
LATIF: Some tiny little speck of a thing just floats in through the window and comes to a rest on one of those Petri dishes.
MARYN MCKENNA: And so a few weeks later ...
LATIF: Fleming, finally back from vacation ...
MARYN MCKENNA: He needs to use those lab plates again, and he and his assistant go to clean them off.
LATIF: I mean, you'd imagine that he would see some real lush, nice furry ...
ROBERT: [laughs]
LATIF: ... lawn of staph just overflowing.
JAD: Yeah!
LATIF: Right out of the plate.
JAD: Because it's been sitting there for so long.
LATIF: It's been a staph party.
MARYN MCKENNA: But on one of the plates that they pick up, they realize that it's almost polka dot. It's got little dead zones all over it.
LATIF: Little patches where the staph is dead.
ROBERT: Dead patches.
JAD: Dead zones.
ROBERT: So something blew through the window, landed in the dish, and starts killing the bacteria?
LATIF: Yeah. And so when Fleming looks down at his plate, he sees that at the center of these, you know, staph dead zones, there's a ...
MARYN MCKENNA: Tiny speck of natural mold.
JAD: Ooh.
ROBERT: Of mold.
MARYN MCKENNA: And they realize that that mold is expressing a compound that is killing the staph around it.
LATIF: It's, like, emanating rays of death.
JAD: What was the compound?
LATIF: That compound was called ...
MARYN MCKENNA: Penicillin.
LATIF: The first true antibiotic.
MARYN MCKENNA: Infectious diseases that had been killing people for as long as we had been people suddenly could be stopped.
JAD: And it just blew in through the window?
MARYN MCKENNA: That is the—that is the story that's always been told.
LATIF: However it got there, it was—it was amazing. It was a miracle.
ROBERT: It was called a miracle drug, right?
MARYN MCKENNA: I mean, it was just—it really was a moment when the world changed, when Fleming was put on the cover of TIME Magazine.
LATIF: This is 1944, height of World War II.
MARYN MCKENNA: It was a picture of his face, and the banner on the cover said, "His penicillin will save more lives than war can spend."
LATIF: But—and this is—I had no idea about this. Virtually at the exact same time when Fleming's face is on the cover of TIME Magazine, like two months later, this Stanford researcher publishes that he has found five different strains of staph that do not respond to penicillin.
JAD: Really?
LATIF: Yeah.
JAD: This is happening while he's on the cover?
LATIF: Virtually the exact same moment.
MARYN MCKENNA: And it's the first sign that staph has responded to the penicillin in the world by developing resistance.
SOREN WHEELER: It's almost like ...
JAD: That's our producer, Soren Wheeler.
SOREN: ... the era of penicillin was over before it began.
MARYN MCKENNA: Almost before it began.
LATIF: Before it's even released to the general public.
JAD: Wow!
MARYN MCKENNA: And that penicillin-resistant staph moves across the globe.
LATIF: And in 1957 in Cleveland, some scientists gather together ...
MARYN MCKENNA: And they are in a panic. They have no idea why they've lost the antibiotic miracle so quickly.
LATIF: So scientists across the globe put their brains together and try to come up with a new drug.
MARYN MCKENNA: The next amazing thing.
LATIF: And in 1960 they get it.
MARYN MCKENNA: Methicillin.
LATIF: And it works!
MARYN MCKENNA: For about 11 months.
SOREN: 11 months?
JAD: Whoa!
LATIF: And so we started this arms race.
MARYN MCKENNA: There was a bug, and then there was a drug that took care of it.
LATIF: [laughs]
MARYN MCKENNA: And then there was a better bug.
SOREN: Drug, bug, drug, bug.
MARYN MCKENNA: Right, exactly.
LATIF: I actually found this list. Do you wanna hear it?
JAD: Yeah.
LATIF: Okay. So streptomycin, 1943, resistance 1948. Methicillin, 1960, resistance 1961. Clindamycin, 1969, resistance 1970.
JAD: Wow!
MARYN MCKENNA: You can think of it as leapfrog, or you can think of it as a game of whack-a-mole.
LATIF: Ampicillin, 1961, then 1973. So that's a little—carbenicillin, released 1964, resistance 1974.
JAD: They're getting better. They're getting better.
MARYN MCKENNA: There were always more drugs. You know, the drug development was doing really well for a really long time.
LATIF: Piperacillin, introduced 1980, resistance 1981.
MARYN MCKENNA: But after the year 2000, drug companies begin to realize it's not really in their best interest to make antibiotics anymore.
LATIF: And the end I have on this list is linezolid, which is introduced 2000, resistance 2002.
JAD: Wow.
LATIF: And there are a few more, but you get the idea.
MARYN MCKENNA: Antibiotic approvals, the entry of new drugs to the market, just kind of fell off a cliff.
SOREN: Why?
MARYN MCKENNA: Well, it takes 10 years and a billion dollars to get to the point where the drug is marketable.
LATIF: But as soon as you get the drug on the market ...
MARYN MCKENNA: The resistance clock is running.
LATIF: So you probably won't make your money back. And as you've probably heard, we now have these situations ...
[NEWS CLIP: A frightening new warning from the Centers for Disease Control about the spread of a string of germs that are ...]
MARYN MCKENNA: Where literally nothing works.
[NEWS CLIP: ... so-called superbugs are now turning up in hospitals in 40 different states.]
MARYN MCKENNA: And the patient dies.
LATIF: There are now bugs that can resist all of our drugs.
MARYN MCKENNA: I've seen physicians break down weeping over this. It's not the way that medicine is supposed to fail anymore, but it does.
SOREN: I mean, I know that—that possibly the origin story of penicillin is apocryphal, so this is all a little suspect but, you know, just to enjoy imagining for a moment, like, it just seems like if that happened, let's just open up a bunch more windows. Just something oughta blow in.
MARYN MCKENNA: But we could wait a long time, right? I mean, we had—staph had been around ...
LATIF: Right.
MARYN MCKENNA: ... for millennia before 1928.
LATIF: Well actually, there is this story about these two women who did open a window to an alien and distant land. And actually in a way it's a story about reimagining the past, but to me it's a—it's a story about a friendship. Okay, so you have ...
CHRISTINA LEE: Hello, I'm Dr. Christina Lee.
LATIF: ... Christina.
CHRISTINA LEE: And I'm an associate professor in Viking studies at the School of English at the University of Nottingham.
LATIF: She's a historian. And then you also have ...
FREYA HARRISON: Hi, I'm Freya Harrison.
LATIF: ... Freya.
FREYA HARRISON: I'm a research fellow in the Centre for Biomolecular Sciences at the University of Nottingham.
LATIF: And Freya? Freya's a microbiologist. She studies bacteria. We'll start with her.
FREYA HARRISON: Okay. So most of my work is about sort of looking at how bacteria evolved during very, very long-lived infections. But ...
[ARCHIVE CLIP, Viking re-enactment: Argh!]
FREYA HARRISON: My—my big hobby is Anglo Saxon and Viking reenactment.
[ARCHIVE CLIP, Viking re-enactment: Hold!]
FREYA HARRISON: So I have purely a sort of amateur interest in history, and mainly in dressing up as a warrior, and going to fight club every Wednesday night and learning to use the weapons.
ROBERT: Really? [laughs]
FREYA HARRISON: Yep.
LATIF: So this is actually not Freya's group. This is a group in New Jersey. But basically they do the same thing: hundreds of people go out into, you know, some field with some dulled weapons.
FREYA HARRISON: Everything from swords to spears, axes. And we give each other a jolly good bashing and have a good time! [laughs] Well it was—it was really a nice sort of coincidence, really.
LATIF: 2012. A few years after finishing her doctorate, Freya goes off to work at the University of Nottingham.
FREYA HARRISON: Nottingham's one of the places in the UK not only for microbiology, but for sort of Anglo-Saxon and Viking history.
LATIF: And she goes there to study microbes, but she figures, "Hey, why not while I'm here, brush up on my Old English?"
FREYA HARRISON: [speaking Old English] I'd studied some Old English to a level where I could sort of read and speak a little bit. [speaking Old English]
LATIF: But she figured hey, she could—she could be better. And if she did, she would get deeper into the whole reenactment thing.
FREYA HARRISON: So I rather cheekily emailed the School of English's Old English reading group.
LATIF: That's where she met Christina.
CHRISTINA LEE: Yes!
LATIF: The historian.
CHRISTINA LEE: And I thought Freya was ...
LATIF: At one point, Christina the historian asks Freya, like, "What do you do?" And Freya said, you know, "My day job is that I'm a microbiologist, but on evenings and weekends I'm a history nerd." And Christina said the moment she heard that ...
CHRISTINA LEE: I just kind of thought I've found my kindred spirit here.
LATIF: Because she was like, "Wow, I'm like your mirror image because I'm a historian by day, but by night I'm a microbiology nerd."
CHRISTINA LEE: I've been interested in infectious disease for quite a long time, which I don't—I don't find any kind of friends in my department.
LATIF: So eventually they start talking about historical diseases, so, like, how would people back then have treated something like, you know, Ebola? Freya is especially interested in this, because she, for her historical reenactment, is developing this nun character who goes off and heals people. But anyway, so they're talking back and forth, and then to cut a long story short, they find themselves both interested in this one particular book.
CHRISTINA LEE: It's known as Bald's Leechbook. So this is probably 1,100 years old.
ROBERT: Bal—is it B-A-L-D?
CHRISTINA LEE: It is, indeed.
ROBERT: And leech, like leech, like a—like a leech, like a little worm that grabs onto your—and sucks your blood?
CHRISTINA LEE: [laughs] No. No, it comes from the Old English word "lǣċe," which is actually a healer or a doctor.
FREYA HARRISON: So the little squiggly animals are called leeches because they're medicinal, not the other way around. [laughs]
ROBERT: Oh!
LATIF: So the doctor wasn't named for the leech, the leech was named for the doctor? [laughs]
FREYA HARRISON: Exactly, yeah.
JAD: And Bald is the—is a man? The guy who wrote the book?
FREYA HARRISON: We think it's a guy. We think it's a guy's name.
JAD: And what is this book?
LATIF: So it's kinda like this old healer's handbook. It's filled with these potions and cures.
CHRISTINA LEE: The original manuscript is in the British Library.
LATIF: Locked away.
FREYA HARRISON: But 21st century, very kind people have digitized the original Old English text and—and put it online.
LATIF: So Christina and Freya bring it up, and they start going through all the remedies.
CHRISTINA LEE: And, you know, it describes to you remedies for stuff that is a little bit different.
FREYA HARRISON: You know, things like possession by the devil.
LATIF: Which, according to this Leechbook, the remedy for someone who is possessed by the devil is you make this kind of like foul brew, you make them drink it, and it'll make them vomit out the devil.
CHRISTINA LEE: And then things like, how shall we say, make your husband more physically attentive?
LATIF: [laughs]
CHRISTINA LEE: Or less physically attentive? Whichever you—whichever direction you need to moderate it.
ROBERT: Pig's blood, I hope. Or toad blood.
LATIF: Actually, it's just you boil a plant in some water and give it to the guy.
ROBERT: Oh.
LATIF: Yeah. So Freya and Christina are going through this Leechbook looking for some kind of wound.
FREYA HARRISON: Something that was clearly an infection.
LATIF: Some pus-y something?
FREYA HARRISON: We could clearly say that's bacterial.
LATIF: And eventually, they find an entry ...
FREYA HARRISON: Where at the end of the recipe, it says in Old English ...
FREYA HARRISON: "Sé betst lǣċedōm." The best medicine.
LATIF: The best medicine.
ROBERT: Hmm.
LATIF: Yeah, move over laughter.
FREYA HARRISON: Yeah. And we thought, how can we not try this one? [laughs]
LATIF: What was the best medicine for?
FREYA HARRISON: So it said it was for a lump in the eye.
CHRISTINA LEE: It's actually called "wén" in Old English.
FREYA HARRISON: Yeah. These days if you get a—of course, that could be something like a wart, right?
LATIF: Hmm.
FREYA HARRISON: But there is a suggestion by archaeologists that eye infection was—was rife amongst the Anglo Saxons.
LATIF: Really?
FREYA HARRISON: Because you lived in buildings where you—you have smoke going on. You lived cramped together. So it could also be a sty.
LATIF: What is a sty?
FREYA HARRISON: It's an infection of an eyelash follicle.
ROBERT: You rub it and it itches, and then it gets swollen.
FREYA HARRISON: Yeah, and it causes quite a nasty red lump.
ROBERT: It's a sty in your eye.
LATIF: Sty in your eye. Now it just so happens that the bacteria that causes the sty in your eye is ...
FREYA HARRISON: Staphylococcus aureus.
LATIF: Staph.
JAD: Oh, the same stuff as the Mr. Window Man. Penicillin man.
LATIF: Exactly.
FREYA HARRISON: And we just thought, wouldn't it be nice to have a bit of spare time and had a couple of hundred quid to buy the ingredients and just give this a go?
CHRISTINA LEE: Yes, let's give it a try.
FREYA HARRISON: You know, why the hell not?
LATIF: And a matter of fact ...
LATIF: Look at this place!
LATIF: ... we thought that too.
MATT KIELTY: Studio.
LATIF: Not bad at all.
LATIF: Recently, producer Matt Kielty and I went to my tiny apartment in the city, and ...
MATT: All right.
LATIF: ... we tried to cook it up too.
MATT: Are you ready to cook?
LATIF: Oh, I'm ready to cook. [laughs]
FREYA HARRISON: I've got this recipe here if you'd like it.
LATIF: Oh, awesome. Yeah. Yeah, yeah. Please read it. Go for it.
FREYA HARRISON: Okay. It goes like this ...
[ARCHIVE CLIP, speaking Old English]
LATIF: That's the first line of the recipe. And right off the bat for Christina and Freya, there's a problem. That first ingredient ...
FREYA HARRISON: The word, "cropléac."
CHRISTINA LEE: "Cropléac."
[ARCHIVE CLIP, [Cropléac.]]
FREYA HARRISON: Christina said was quite difficult to translate.
CHRISTINA LEE: Nobody quite knows, you know, what it is. But luckily ...
LATIF: Just a couple words over was a clue.
[ARCHIVE CLIP, [Gārlēac.]]
LATIF: A second ingredient.
FREYA HARRISON: Garlic, which is an allium species. And cropléac, we know this was another allium. That's what the dictionary of Old English tells us.
LATIF: So they figured probably what they were dealing with was an onion or a leek.
FREYA HARRISON: But we didn't know which one. So we thought okay, we'll try one that has onion and one that has leek.
LATIF: Now the recipe doesn't call for this, but we did it anyway.
LATIF: Peel the onion. Chop it up. The same with the garlic.
CHRISTINA LEE: And the recipe, it doesn't tell you how much. It just tells you equal amounts of.
LATIF: So you take out the measuring cups, you measure out equal amounts.
LATIF: Yeah, equal amounts into the pestle.
LATIF: And then after that ...
MATT: Okay.
LATIF: It says ...
[ARCHIVE CLIP: [speaking Old English]]
LATIF: ... "Pounded well together."
MATT: Okay.
CHRISTINA LEE: You have to really pound it, and pound it Freya did.
FREYA HARRISON: Yeah. Yeah, so lots of time with a mortar and pestle, muscles built up from wielding a sword for pounding the ingredients.
LATIF: Look, it's starting to be more of a mush.
LATIF: Third ingredient?
FREYA HARRISON: The next one was definitely something you wouldn't have knocking around in your kitchen.
[ARCHIVE CLIP: [speaking Old English]]
FREYA HARRISON: Ox gall.
LATIF: Ox gall.
FREYA HARRISON: Bovine bile from a—from a cow's gallbladder.
ROBERT: [laughs] What, do you have to kill the cow and then go reach ...
FREYA HARRISON: No, it's actually a very standard ingredient in microbiology labs.
MATT: Ox bile.
LATIF: You can but should not just buy it on the internet.
MATT: Here we go, here we go.
LATIF: And so you take the ox bile, add it to the onion and garlic ...
FREYA HARRISON: And then the fourth ingredient ...
[ARCHIVE CLIP: [speaking Old English]]
FREYA HARRISON: ... wine.
LATIF: It's wine time. Red wine? White wine? Like, what kind of wine are we talking about here?
FREYA HARRISON: Well, this is the thing. So we had quite a discussion about what type of wine should we use, and we don't know really, did they have red wine? Did they have white wine? What was the alcohol content? But I did a bit of—bit of detective work.
LATIF: And she figured out that the monastery where this Leechbook was written, well, they—she figured out where their vineyard was.
FREYA HARRISON: And just down the road, there's this modern organic vineyard.
LATIF: So they used that wine.
[ARCHIVE CLIP: [speaking Old English]]
LATIF: I just want to point out how difficult it is to find English wine. We had to use Italian. But ...
[ARCHIVE CLIP: [speaking Old English]]
LATIF: ... once you get all that stuff together, you're onto the final ingredient.
FREYA HARRISON: The fifth ingredient was actually the—you're specifically told that you have to mix these ingredients together in a brass or a bronze pot. I don't have one. [laughs] So we had to sort of add pieces of—you know, of copper that would've been available to people at the time.
LATIF: So they had to do some research, but they figured out that the copper of today that is most like the copper of a millennium ago was actually ...
FREYA HARRISON: Cartridge brass, which is what's used as standard in plumbing fittings.
LATIF: Dropped a few pennies in there.
LATIF: We actually used pennies.
MATT: Do I stir it? I think I stir it.
LATIF: This is like the world's worst cooking show.
MATT: [laughs]
FREYA HARRISON: And it looks and smells like quite a nice—quite a nice summer soup. [laughs]
LATIF: Oh!
MATT: Oh, it looks awful.
LATIF: Oh, that's so gross! Clearly, we botched this whole thing.
[ARCHIVE CLIP: [speaking Old English]]
LATIF: And finally ...
MATT: All right, so we're gonna cover it.
LATIF: Okay, we're covering it.
LATIF: ... the directions say we have to let the whole thing sit for a while.
FREYA HARRISON: It has to be stored for nine days and nights.
MATT: Okay. That's it.
ROBERT: One day goes by. Two days, three, four, five.
LATIF: Six, seven, eight, nine.
MATT: All right. Nine days later.
LATIF: All right. Here we go. You ready?
MATT: Mm-hmm.
LATIF: All right, here we go.
FREYA HARRISON: And ...
[ARCHIVE CLIP: [speaking Old English]]
FREYA HARRISON: Then you have to strain it through a cloth. The liquid that comes off, you apply to the person's eye.
MATT: Oh, the liquid!
[ARCHIVE CLIP: [speaking Old English]]
CHRISTINA LEE: Yeah, with a feather.
[ARCHIVE CLIP: [speaking Old English]]
FREYA HARRISON: With a feather.
LATIF: Now clearly, we didn't have any staph to try this out on, but Freya in her lab, she made these mock wounds.
FREYA HARRISON: With these little plugs of—of collagen, so it's a bit like jelly.
LATIF: Basically it's like a—like a goopy substance made to be kind of like a flesh wound.
FREYA HARRISON: And we infect these wounds with bacteria, with the staph.
LATIF: Then they put this thousand-year-old recipe that had been standing there for nine days, they put it on the bacteria that was in the fake wound.
FREYA HARRISON: We'd—obviously, we didn't think this was going to work.
CHRISTINA LEE: No.
FREYA HARRISON: We thought, you know, well given the ingredients, we might see some small killing effect on the bacteria, but it won't be anything to write home about.
LATIF: They thought maybe it'd kill 10 percent, 20 percent of the bacteria. But then when they came back the next day ...
FREYA HARRISON: It was a staph massacre.
LATIF: It went on a rampage! It went on a staph rampage.
FREYA HARRISON: It was killing, you know, 99.99999 percent of these bacterial cells.
LATIF: What?!
FREYA HARRISON: Yeah. First we thought we made some sort of mistake and this was some kind of fluke, you know? We'd accidentally mixed up our plates or mislabeled something.
LATIF: So they rerun the entire experiment again. They grab the ingredients, mash them up, put them on some bacteria, and it happens again!
FREYA HARRISON: Just absolutely wiped out the bacteria in these fake wounds.
CHRISTINA LEE: Killed them dead.
LATIF: Then they tried a third time, and a fourth, and a fifth, and it worked every time!
FREYA HARRISON: And this is—this is just something you really don't see in your career as a microbiologist. [laughs]
LATIF: And eventually, they escalated from just regular staph to MRSA. To the methicillin-resistant staph. And this is one of the bad ones.
[NEWS CLIP: A superbug. New government data estimate that about 2,000 people are dying of community-based MRSA every year.]
[NEWS CLIP: This one is very dangerous.]
LATIF: So Christina and Freya, they sent some of Bald's brew to one of their collaborators in the States.
FREYA HARRISON: Our collaborator Kendra Rumbaugh in Lubbock, in Texas.
LATIF: Kendra took the stuff, put it on some MRSA bacteria, and then a week later sent Freya and Christina an email.
FREYA HARRISON: And I think it was actually a three-word response. I think she just simply said ...
[ARCHIVE CLIP: [speaking Old English]]
FREYA HARRISON: What the [bleep]. [laughs]
LATIF: Bald's best medicine had just wreaked havoc on the MRSA. It killed 90 percent of them.
FREYA HARRISON: It's just—it's beyond our wildest dreams.
LATIF: Now Freya and Christina made very clear that this is not yet a miracle drug. I mean, it's not even being tested in humans.
CHRISTINA LEE: So absolutely do not do this at home.
LATIF: They don't even know if this is safe.
FREYA HARRISON: It might be that if you don't do it in exactly the way we did, nasty fungus could grow in it, give you a worse infection.
LATIF: So ...
LATIF: We should not have done this.
MATT: [laughs]
LATIF: Matt and I, we dumped ours down the drain. But the thing about this whole story that is so intriguing and so cool to me is this time travel thing, which is so strange. Like, it's like, the idea that something a thousand years ago, like a bullet forged a thousand years ago, we could—we could use it now and that it could work. That—the time travel dimension of that is so weird to me. It kind of makes you think differently about, I don't know, progress.
[ARCHIVE CLIP, presenter: So without much further ado, Dr. Christina Lee and Dr. Freya Harrison, and they're going to talk to us about some ancient biotics.]
[applause]
LATIF: For example, just a few weeks ago, Freya and Christina got up in front of the Royal Society of Chemists.
[ARCHIVE CLIP, Christina Lee: Thank you very much, and it is an absolute pleasure to be here.]
LATIF: Large hotel conference room, hundred or so people. Freya actually got up on stage dressed as a nun.
[ARCHIVE CLIP, Freya Harrison: Okay, so this is one interpretation of what an Anglo Saxon scientist may have looked like.]
LATIF: And they presented the results.
[ARCHIVE CLIP, Freya Harrison: Next ingredient is particularly ...]
LATIF: They did the cooking demo. And then at some point, Christina said something really interesting. She was like, "Okay sure, we want to write this off because it has demons and dragons and elves in it, but are we sure that we know what they meant by those words? Like, for example ...
[ARCHIVE CLIP, Christina Lee: There are remedies which ask you, "Sing four Ava Marias."]
LATIF: And we would say, "Oh, that's so superstitious. This is all in their heads."
[ARCHIVE CLIP, Christina Lee: But there again, we should also remember this is a period when people do not have watches. You do not have your nurse, you know, so they've got the watch. Everybody knows the Ava Maria. Everybody knows the length of an Ava Maria.]
LATIF: So maybe it's—maybe it's, take this medicine and wait 20 minutes. And I know how to standardize 20 minutes, which is ...
[ARCHIVE CLIP, Christina Lee: Three Ava Marias, four Ava Marias, may actually be time periods.]
LATIF: So it ...
ROBERT: Oh, that's fascinating.
LATIF: It may appear one way, and it's—it in fact could be a totally different way.
JAD: It suggests that in order to time travel, you have to somehow—God, it's like we don't even have the language to be able to understand what they were doing.
LATIF: There's a ...
JAD: And how effective it was.
LATIF: There's a phrase. "The past is a foreign country."
CHRISTINA LEE: We need to learn the language of the doctors of that time. We need to kind of be a little bit less dismissive, and learn a little bit more, you know, stuff from them. I learned a bit of humility this way.
LATIF: But here's the reason why this is so confusing to me.
FREYA HARRISON: Hmm.
LATIF: So 1,100 years is a crazy long time for humans, and for bacteria that's like a exponentially crazy long time.
FREYA HARRISON: Yeah.
LATIF: So how is it that something that this man Bald was doing to these bacteria then—like, it's not even the same bacteria.
FREYA HARRISON: Yeah.
LATIF: How could that even work?
FREYA HARRISON: That—that's an awesome question. So one thing we've got to think about is well, why did these medicines drop out of use? And maybe it's because when they were used, the bacteria evolved resistance. But now, a thousand years later, when these medicines have not been used, you would expect that resistance to be lost.
LATIF: This is something that Maryn McKenna mentioned to Soren and I, that sometimes when you take a drug out of circulation ...
MARYN MCKENNA: Sometimes resistance will decline. That doesn't always work, but sometimes resistance does decline. So if we had been using this compound through the ensuing thousand years, then maybe it wouldn't work.
ROBERT: So there's an interesting discovery there. Like, that what worked once, and then was resisted, you give it a rest, it can work again. And then it will be resisted, and you put it to rest. And if you had enough different—if you could go to different places and the different path—you could go to China, where they now got all these people studying Chinese cures and Arab cures, you could come up with a—with a rich historical cocktail of armamentarium that will work if you bring 'em in, take 'em out. Bring 'em in, take 'em out. And the whole world—the whole world of the past then becomes the fruit of your future, sort of.
SOREN: So it's also poss—like, now I have suddenly an image that it's possible that ...
JAD: This is Soren Wheeler, by the way, in conversation with Maryn McKenna and Latif.
SOREN: That a thousand years ago, these folks went through what we went through with penicillin, in that they—this guy wrote something in the book, and it's actually called the best medicine. He probably got on the cover of whatever their version of TIME was.
MARYN MCKENNA: He got their Nobel Prize. [laughs]
SOREN: And everybody celebrated. And then years later styes were coming back and the garlic wine didn't work anymore, and they stopped using it. And it got put away, and then here we are and we discover it, and it's been put away long enough that—like, and now I'm thinking about future—some future civilization digs up an old medical textbook that was in some dusty whatever and discovers penicillin. And it works. Did we—did I lose you on that, Maryn?
MARYN MCKENNA: No, no. I'm still with you. I'm just—I don't know how—it just seems like such a great hypothetical construction, I just didn't really know what I could add to it. Sorry. [laughs]
SOREN: [laughs] Sorry I took over.
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