May 5, 2021

Staph and Gamma

Two stories of surprisingly simple scientific discoveries one that seems straight out of sci-fi, and the other, directly from the past. 

First, we head to the lab of neuroscientist Li-Huei Tsai to discover the power of flashing lights on an Alzheimer’s-addled (mouse) brain. In this segment, Li-Huei tells us about her team’s latest research, which also includes flashing sound, and ways in which light and sound together might retrieve lost memories. This new science is not a cure, and is far from a treatment, but it’s a finding so … simple, you won’t be able to shake it. Come join us for a lab visit, where we’ll meet some mice, stare at some light, and come face-to-face with the mystery of memory. We can promise you: by the end, you’ll never think the same way about Christmas lights again. Or jingle bells.

Then, what happens when you combine an axe-wielding microbiologist and a disease-obsessed historian? A strange brew that's hard to resist, even for a modern day microbe. In the war on devilish microbes, our weapons are starting to fail us.  The antibiotics we once wielded like miraculous flaming swords seem more like lukewarm butter knives. But today we follow an odd couple to a storied land of elves and dragons. There, they uncover a 1000-year-old secret that makes us reconsider our most basic assumptions about human progress and wonder: What if the only way forward is backward?

 

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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 going to play a show that Molly Webster and Robert Krulwich did a few years back that at the time - this was 2016 - was breaking news, but it also includes some updates that came out in about 2020. So I'm going to let them take it from here.

(SOUNDBITE OF ARCHIVED BROADCAST)

ROBERT KRULWICH: Hi. I'm Robert Krulwich.

MOLLY WEBSTER: I'm Molly Webster.

ROBERT KRULWICH: This is RADIOLAB. And today...

(SOUNDBITE OF MUSIC)

MOLLY WEBSTER: We've got breaking news, Robert Krulwich.

ROBERT KRULWICH: On - break - this is something we've never done before.

MOLLY WEBSTER: Never done before.

ROBERT KRULWICH: Well, does anybody know about this yet?

MOLLY WEBSTER: Well, it is a new bit of research. It's being published today.

ROBERT KRULWICH: What's this thing about?

MOLLY WEBSTER: Oh, this is a discovery about Alzheimer's disease, which I think at this point is something that affects basically every family.

ROBERT KRULWICH: Affected my family, yeah.

MOLLY WEBSTER: 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...

ROBERT KRULWICH: Oh, yeah.

MOLLY WEBSTER: ...And poking at it in this super simple way and getting this bizarre result.

LI-HUEI TSAI: Hello?

MOLLY WEBSTER: Hello, hello.

LI-HUEI TSAI: Hi, Molly.

MOLLY WEBSTER: Hi.

LI-HUEI TSAI: Hi. How are you?

MOLLY WEBSTER: 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's pretty cool, though. We ended up deciding to sign a nondisclosure 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 the director of the Picower Institute for Learning and Memory at MIT.

MOLLY WEBSTER: Holy crap. You're the director. How do you have time to do all of that?

LI-HUEI TSAI: I know. That's a good question (laughter).

MOLLY WEBSTER: She is - like, a badass is what she is.

ROBERT KRULWICH: (Laughter).

LI-HUEI TSAI: But this is a piece of work I'm very proud of. So historically, people work on Alzheimer's really focus a lot on...

MOLLY WEBSTER: 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 WEBSTER: ...The genetics of the disease, so the genes that predispose you, maybe, to Alzheimer's.

LI-HUEI TSAI: ...Or...

MOLLY WEBSTER: The brain chemistry and how Alzheimer's affects the chemicals in the brain.

LI-HUEI TSAI: ...Molecular pathological features.

MOLLY WEBSTER: 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 WEBSTER: Her work all centers around something called...

LI-HUEI TSAI: The gamma frequency.

ROBERT KRULWICH: The gamma frequency?

LI-HUEI TSAI: Gamma.

MOLLY WEBSTER: And what is - I'm like - it feels like something from "Battlestar Galactica."

(LAUGHTER)

MOLLY WEBSTER: So I don't think it's that (laughter).

LI-HUEI TSAI: So this gamma - so-called gamma...

MOLLY WEBSTER: You could think of it as a particular beat...

(SOUNDBITE OF MUSIC)

MOLLY WEBSTER: ...In your brain.

ROBERT KRULWICH: A beat in the brain?

MOLLY WEBSTER: Yeah.

LI-HUEI TSAI: Yeah.

ROBERT KRULWICH: Which means what exactly?

MOLLY WEBSTER: Well, just to oversimplify one of the most complicated things in the known universe...

ROBERT KRULWICH: (Laughter) OK. Please do.

MOLLY WEBSTER: 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 WEBSTER: 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 WEBSTER: And the way they do that is they fire.

LI-HUEI TSAI: Yes.

MOLLY WEBSTER: An electrical signal will go through them, and it'll, like, zap another neuron, and it'll turn it on. And then it'll - like, 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 WEBSTER: All together on the same...

(SOUNDBITE OF MUSIC)

MOLLY WEBSTER: ...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 KRULWICH: What are they doing?

MOLLY WEBSTER: That I have no idea. I just...

ROBERT KRULWICH: And all this is going on in your head simultaneously?

MOLLY WEBSTER: 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.

(SOUNDBITE OF MUSIC)

ROBERT KRULWICH: Huh.

MOLLY WEBSTER: 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 WEBSTER: You're, like, trying to find your way home from the subway station or if you're in a new city, you know, 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 WEBSTER: 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 WEBSTER: 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, like, the power of gamma is reduced.

LI-HUEI TSAI: Not all the neurons can be recruited to oscillate at the gamma frequency.

MOLLY WEBSTER: It's still there. It's just quieter. It's like you turned the volume down.

LI-HUEI TSAI: Right.

ROBERT KRULWICH: 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 got Alzheimer's, kind of gets saggy or tired.

MOLLY WEBSTER: 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 KRULWICH: The stuff that gucks up your brain and makes it hard to think.

MOLLY WEBSTER: Yeah, yeah, yeah, totally. It's like cobwebs in the brain. And then the connections between neurons gets all muddied, and...

ROBERT KRULWICH: Yeah.

MOLLY WEBSTER: ...Immune cells get messed up. But Li-Huei Tsai was like, forget all that.

(SOUNDBITE OF MUSIC)

MOLLY WEBSTER: What would happen if I just bring the gamma back?

LI-HUEI TSAI: Yeah. We decided to just manipulate gamma oscillations.

ROBERT KRULWICH: And how do you do that?

MOLLY WEBSTER: Well...

Hello, hello, hello, hello, hello, hello, hello, hello.

...Technology.

Hi, this is Molly. Hi, hi, hi.

Technology you can find at the Massachusetts Institute of Technology.

We're walking into the Picower Institute. It's a...

Wow.

...Big, shiny glass building.

LI-HUEI TSAI: Molly, hi. Nice to meet you.

MOLLY WEBSTER: 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 WEBSTER: And so Li-Huei led me down the hall to this tiny room.

LI-HUEI TSAI: OK. So...

MOLLY WEBSTER: So here's what they did. They get some ice.

LI-HUEI TSAI: We started off with a mouse model.

MOLLY WEBSTER: Mice that have an early stage of Alzheimer's disease.

LI-HUEI TSAI: With multiple notable defects.

ROBERT KRULWICH: Do they have the gunky plaque stuff in them yet, or is that later?

MOLLY WEBSTER: No, but they do have...

LI-HUEI TSAI: Elevated levels of beta amyloid peptides.

MOLLY WEBSTER: 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 WEBSTER: So to do that...

(SOUNDBITE OF MUSIC)

MOLLY WEBSTER: ...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 WEBSTER: At 40 beats per second.

LI-HUEI TSAI: Gamma frequency.

MOLLY WEBSTER: 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 WEBSTER: ...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 WEBSTER: And they would keep these cells firing at gamma.

LI-HUEI TSAI: For one hour.

MOLLY WEBSTER: Firing and firing and firing and firing and firing.

LI-HUEI TSAI: And then after one hour...

MOLLY WEBSTER: 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...

(SOUNDBITE OF MUSIC)

LI-HUEI TSAI: To our much surprise...

MOLLY WEBSTER: They were not expecting this at all.

LI-HUEI TSAI: We found...

MOLLY WEBSTER: 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 KRULWICH: A half of the...

MOLLY WEBSTER: Yeah.

ROBERT KRULWICH: Half?

MOLLY WEBSTER: Half of the stuff was just swept away.

LI-HUEI TSAI: Yes - 40 to 50% reduction of beta amyloid.

MOLLY WEBSTER: That just seems crazy.

LI-HUEI TSAI: This is crazy.

MOLLY WEBSTER: Yeah.

LI-HUEI TSAI: I mean, we were just so surprised.

ROBERT KRULWICH: Do they know why the flood of light would...

MOLLY WEBSTER: Yeah, yeah. So...

LI-HUEI TSAI: Turn out...

MOLLY WEBSTER: ...The pulsing light somehow triggered the brain's cleanup crew.

LI-HUEI TSAI: Microglia.

MOLLY WEBSTER: These cells in the brain that are called microglia.

LI-HUEI TSAI: You can say they're the janitors of the brain.

MOLLY WEBSTER: And in a normal brain, these janitor cells usually gobble up the gunk.

LI-HUEI TSAI: But in Alzheimer's disease, it's known that microglia - they don't sort of function normally anymore.

MOLLY WEBSTER: It's like these janitors just sort of...

LI-HUEI TSAI: Stop cleaning up.

MOLLY WEBSTER: And go on strike.

ANTHONY MARTORELL: There we go. OK. Cool.

MOLLY WEBSTER: OK, so we're looking at a screen that's now flat. It's not...

When I was at MIT, one of Li-Huei's grad students...

ANTHONY MARTORELL: My name is Anthony Martorell, second year.

MOLLY WEBSTER: ...Was showing me side-by-side comparisons of these mice brains on a screen.

ANTHONY MARTORELL: Can you guess what that is?

MOLLY WEBSTER: Which part?

ANTHONY MARTORELL: The green things.

MOLLY WEBSTER: Microglia.

ANTHONY MARTORELL: Microglia, yeah.

(LAUGHTER)

MOLLY WEBSTER: And you see...

LI-HUEI TSAI: After one hour of gamma...

MOLLY WEBSTER: Wow. So that...

LI-HUEI TSAI: ...The microglia, the cell, seems a lot bigger.

MOLLY WEBSTER: Clearly see these round bodies.

LI-HUEI TSAI: Yeah.

MOLLY WEBSTER: Yeah.

LI-HUEI TSAI: And also, their belly (ph) seems to have more amyloid.

MOLLY WEBSTER: Oh, like they're doing more eating.

LI-HUEI TSAI: Yes. They go back to eat more amyloid again.

MOLLY WEBSTER: It's like somehow making the neurons fire turned on the sanitation system in the brain.

LI-HUEI TSAI: But the most the wild results...

MOLLY WEBSTER: Wait. There's more wild?

LI-HUEI TSAI: Oh, my God. You got to hear this...

MOLLY WEBSTER: (Laughter) OK, OK.

LI-HUEI TSAI: ...Because what I'm about to tell you - you may say, no, I don't believe it. It's science fiction. OK.

MOLLY WEBSTER: So one of the things Li-Huei and her team were starting to think was that drilling in fiber-optic cable...

LI-HUEI TSAI: Is very invasive, right?

MOLLY WEBSTER: You'd never be able to do that on a human.

LI-HUEI TSAI: Exactly. So we started to say...

MOLLY WEBSTER: Well, what if we can get the light into the brain in a different way? Like, maybe we could go through the eyes.

ROBERT KRULWICH: So the hole in your head would be your eyes instead of a hole in your head?

MOLLY WEBSTER: Yes.

LI-HUEI TSAI: Yes.

MOLLY WEBSTER: So Li-Huei and her team created what I like to think of as the flicker room.

(SOUNDBITE OF MUSIC)

MOLLY WEBSTER: Wait. Is this the room?

LI-HUEI TSAI: This is the room.

MOLLY WEBSTER: (Laughter) OK.

It turns out, I learned upon my visit, it is just a storage closet.

You know, you have a - what is this? Just, like, a plastic table.

Very DIY.

ANTHONY MARTORELL: Yeah, it's a plastic table you can buy at Target.

MOLLY WEBSTER: There were some plastic shoebox-sized containers lined up on the table for the mice. And then...

LI-HUEI TSAI: Do you see this strip?

MOLLY WEBSTER: Around the edge of the table...

LI-HUEI TSAI: Basically, surrounding all the cages.

MOLLY WEBSTER: ...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 WEBSTER: 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 WEBSTER: Yeah.

And so we turn off the overhead light in the room so it's very black. And then...

(SOUNDBITE OF MUSIC)

MOLLY WEBSTER: Oh, wow.

The room was now glowing with this white LED light.

ANTHONY MARTORELL: OK, so the light is turning on and off 40 times a second.

MOLLY WEBSTER: It's - so there's - you don't see anything going, like, on or off. It just looks like something's on.

LI-HUEI TSAI: Exactly.

MOLLY WEBSTER: But it kind of feels like my eye is twitching.

LI-HUEI TSAI: Exactly.

MOLLY WEBSTER: And so it's blurring the light a little, just on the edges, though.

LI-HUEI TSAI: Yeah, just on the edges.

MOLLY WEBSTER: And so they put mice in this room for an hour and just let them kind of bathe in this glow.

LI-HUEI TSAI: And guess what?

MOLLY WEBSTER: What?

LI-HUEI TSAI: We look at the amyloid beta levels in the visual cortex, and we found there is a 50% reduction.

MOLLY WEBSTER: Fifty percent?

LI-HUEI TSAI: Fifty percent reduction.

MOLLY WEBSTER: Just from shining light in their eyeballs?

LI-HUEI TSAI: Yes.

ROBERT KRULWICH: Wait a second. They didn't do any drilling in their skulls or anything?

MOLLY WEBSTER: No, no, they didn't drill. They didn't tweak the mouse's brain cells to be sensitive to light. This is just...

ROBERT KRULWICH: They just filled the room with occasional LEDs flashing at a particular frequency?

MOLLY WEBSTER: For an hour.

LI-HUEI TSAI: Now, do you see? (Laughter) Are you going to doubt me? I don't believe it? It's science fiction?

(LAUGHTER)

MOLLY WEBSTER: 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. And 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, like, 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 KRULWICH: Wow.

MOLLY WEBSTER: Half.

ROBERT KRULWICH: Wow.

LI-HUEI TSAI: It's just flickering light in front of the mice.

MOLLY WEBSTER: That's the shock. I mean, that's the shocking thing.

LI-HUEI TSAI: Yeah (laughter).

MOLLY WEBSTER: 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: See - well, you know, that's really the most unexpected and exciting aspect of our study, which is something this simple, yet, you know, it has never been done before, you know? That...

MOLLY WEBSTER: 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.

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 ABUMRAD: So wait. Do we know what it sounds like?

MOLLY WEBSTER: I have it here (laughter).

JAD ABUMRAD: Oh.

MOLLY WEBSTER: So I'm going to hit play.

JAD ABUMRAD: OK.

MOLLY WEBSTER: Oh, my God. It's kind of a crazy sound. (Laughter) I almost don't want to hit play. OK. Three, two, one.

(SOUNDBITE OF GAMMA SOUND)

JAD ABUMRAD: Oh, God.

MOLLY WEBSTER: Yeah.

JAD ABUMRAD: Whoa.

MOLLY WEBSTER: Yeah.

JAD ABUMRAD: 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 WEBSTER: Right? I - the first time I heard it, I, like, ripped my headphones off my head. And then - I then really converted and found it super soothing.

JAD ABUMRAD: I'm not there yet.

MOLLY WEBSTER: OK.

(LAUGHTER)

MOLLY WEBSTER: 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...

JAD ABUMRAD: Yes.

MOLLY WEBSTER: ...In a way that they...

JAD ABUMRAD: Totally.

MOLLY WEBSTER: ...Are playing.

JAD ABUMRAD: And maybe we even want to take it a step further and say, do not use this sound (laughter).

MOLLY WEBSTER: 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 flicker room.

(SOUNDBITE OF ARCHIVED BROADCAST)

ROBERT KRULWICH: If the mouse no longer has quite as much junk in its head, does that mean that it can remember things that happened to it, that it gets mentally more acute?

MOLLY WEBSTER: Yeah. That is their big next research. That's...

ROBERT KRULWICH: So they don't know.

MOLLY WEBSTER: They don't know. That's what they're to - 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. 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 KRULWICH: Oh, really?

MOLLY WEBSTER: Yeah. And we'll get to them. But first, we have to go to a break.

ROBERT KRULWICH: (Laughter) OK.

(SOUNDBITE OF JUSTIN TIMBERLAKE SONG, "SEXYBACK")

JAD ABUMRAD: Hey. Jad, here. We are back, looking back at Molly Webster's piece from 2016, peppering in some updates as we go. We're going to keep rolling here with the original for a beat, and then we'll get more from 2020 Molly and me in a little bit.

(SOUNDBITE OF ARCHIVED BROADCAST)

ROBERT KRULWICH: I'm Robert Krulwich.

MOLLY WEBSTER: I'm Molly Webster.

ROBERT KRULWICH: This is RADIOLAB.

MOLLY WEBSTER: And we're back.

ROBERT KRULWICH: And just before the break, you said that there may be a way to bring a memory back from the Alzheimer's disease, to pull the memory back into place.

MOLLY WEBSTER: Yeah.

DHEERAJ ROY: Why are we so quick to jump to the conclusion that the information was somehow completely gone?

MOLLY WEBSTER: 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 WEBSTER: 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 WEBSTER: So they took some mice that were just starting to lose their ability to remember things. And they thought, OK, let's try to give them a memory.

DHEERAJ ROY: We put them in a box of has a particular smell, some sort of lighting and some texture on their feet.

MOLLY WEBSTER: A little mouse carpet or (laughter)...

DHEERAJ ROY: That's exactly what it is.

MOLLY WEBSTER: Wait. Really?

DHEERAJ ROY: Yeah.

MOLLY WEBSTER: OK.

DHEERAJ ROY: (Laughter).

MOLLY WEBSTER: Mice on carpets, got it.

The point is the box looks and feels and smells different than any other box they would hang out in.

DHEERAJ ROY: And then you give them a light electrical shock.

MOLLY WEBSTER: And the mice, they just freeze.

DHEERAJ ROY: They don't move at all.

MOLLY WEBSTER: ...Which is a sign that they're afraid.

DHEERAJ ROY: They hate the box.

MOLLY WEBSTER: 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 WEBSTER: But...

DHEERAJ ROY: A day or a week later...

MOLLY WEBSTER: When the 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 WEBSTER: 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 KRULWICH: In the fear section.

MOLLY WEBSTER: Near the fear section. So leading on the path to the fear section.

DHEERAJ ROY: So we do this.

MOLLY WEBSTER: And then...

DHEERAJ ROY: Put them back into the box...

MOLLY WEBSTER: The box with the particular lighting and smell and carpet...

DHEERAJ ROY: ...And ask, is there any change in their behavior?

MOLLY WEBSTER: Will they act afraid again?

DHEERAJ ROY: Do they show any more memory? And they did. They showed recovered memory.

MOLLY WEBSTER: Wow.

ROBERT KRULWICH: Whoa.

MOLLY WEBSTER: So that's like, bam, that memory is in there.

DHEERAJ ROY: Exactly. Voila. The behavior is back.

ROBERT KRULWICH: And you can dig up the memory by shining light in the right place?

MOLLY WEBSTER: Yeah.

DHEERAJ ROY: Mmm hmm.

MOLLY WEBSTER: 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...

MOLLY WEBSTER: Oh, OK (laughter).

DHEERAJ ROY: ...What you described.

MOLLY WEBSTER: (Laughter) Well...

DHEERAJ ROY: Just because...

MOLLY WEBSTER: ...That's good (laughter).

DHEERAJ ROY: Because the patient could never tell us, we all assumed the information had to be gone.

ROBERT KRULWICH: Huh.

MOLLY WEBSTER: So one of the things to say is that Dheeraj did tell me that, you know, all of 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 KRULWICH: That might be right, that a memory lost is just lost. But, you know, 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. 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, 10 years. It was a slow act of disappearing that he did where, 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) day - dayenu, day - dayenu, day - dayenu, dayenu, dayenu.

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 just last figment of himself. And it was both horrifying and extraordinary - both, you know.

DHEERAJ ROY: I mean, I think that's the fact that maybe some information still persists. Hopefully some day we could kind of - maybe there's something we could do. But yeah, this is all in my mind at the moment (laughter).

(SOUNDBITE OF MUSIC)

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 WEBSTER: 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 WEBSTER: This is becoming like a mice spa.

(LAUGHTER)

MOLLY WEBSTER: 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-HUEI TSAI: Not just in one particular brain region now - we are seeing across different brain regions.

MOLLY WEBSTER: 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 ABUMRAD: Is it a little bit like a whole bunch of, like, clocks coming into...

MOLLY WEBSTER: Yeah.

JAD ABUMRAD: ...Sync?

MOLLY WEBSTER: Yeah, yeah.

JAD ABUMRAD: Huh.

MOLLY WEBSTER: And imagine thinking it's only going to 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 neural circuitry. And I think this, in turn, can lead to recovery of learning and memory.

MOLLY WEBSTER: 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 ABUMRAD: That's so interesting.

LI-HUEI TSAI: And the mice show very impressive improvement to their cognitive ability.

MOLLY WEBSTER: 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-HUEI TSAI: Yes.

MOLLY WEBSTER: So with all this stuff - super new - so you feel like it's caveat time?

LI-HUEI TSAI: You know, I personally think the most important question is whether humans respond similarly.

MOLLY WEBSTER: 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 WEBSTER: And do you have a thought that, like, why - like, is there a reason that a human neuron might react differently than a mouse?

LI-HUEI TSAI: The thing is, I think especially, you know, in Alzheimer's field, I mean, people got burned a lot. There's so many...

MOLLY WEBSTER: You know, there's like a 99.6% failure rate in moving something that seemed to work in mice to humans in Alzheimer's.

ROBERT KRULWICH: Ninety-nine point six?

MOLLY WEBSTER: Yeah, yeah. That was a study that came out in 2012.

ROBERT KRULWICH: That's a horrible number.

LI-HUEI TSAI: So I just got to be really conservative here.

MOLLY WEBSTER: (Laughter) I'll dial it back. I'll dial it back.

LI-HUEI TSAI: You know, what we have...

MOLLY WEBSTER: Yeah.

LI-HUEI TSAI: ...In mice is just so exciting and so unexpected. But, you know, I'm going to keep my mind open when it comes to humans.

MOLLY WEBSTER: And so here 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 a IRB approved for our first very small-scale study in early-stage Alzheimer's disease subjects.

MOLLY WEBSTER: They're doing a clinical trial with 15 Alzheimer's patients.

JAD ABUMRAD: 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 WEBSTER: Really?

LI-HUEI TSAI: Yeah. So they themselves or their caregiver can turn on the device.

MOLLY WEBSTER: 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 going to see.

LI-HUEI TSAI: You know, we are talking about living, human being.

MOLLY WEBSTER: (Laughter).

LI-HUEI TSAI: It's not that we can just take out the brain and see the microglia or, you know, all of 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 ABUMRAD: And do you have any intel on what they're seeing so far?

MOLLY WEBSTER: Nada. I wish.

LI-HUEI TSAI: I mean, every step of the way, to be quiet honest, it's always a surprise. It's like, oh...

MOLLY WEBSTER: Yeah.

LI-HUEI TSAI: ...This can do - you know, gamma can do this, and gamma can do that.

ROBERT KRULWICH: 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.

MOLLY WEBSTER: (Laughter).

ROBERT KRULWICH: There's so much chance. There's going to be a lot of surprise.

MOLLY WEBSTER: 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, like, beautiful in that.

(SOUNDBITE OF MUSIC)

LI-HUEI TSAI: Yeah, I'm actually setting this up for my Christmas tree.

MOLLY WEBSTER: 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 WEBSTER: Oh, so each individual bulb can travel through colors. But while they're doing that, they're going to be flickering at 40.

LI-HUEI TSAI: Yeah. We're going to have a very therapeutic Christmas. (Laughter).

MOLLY WEBSTER: In the Li-Huei Tsai household, this is the tree in your home?

LI-HUEI TSAI: Yes, yes.

ROBERT KRULWICH: (Laughter).

MOLLY WEBSTER: I want to have an eggnog next to that tree.

ROBERT KRULWICH: Yeah.

JAD ABUMRAD: Hey, I'm Jad Abumrad.

ROBERT KRULWICH: I'm Robert Krulwich.

JAD ABUMRAD: This is RADIOLAB. And today...

ROBERT KRULWICH: Well, today...

JAD ABUMRAD: Yes.

ROBERT KRULWICH: ...The story of an axe-wielding nun coming through a window to smack some staphylococcus and take you back to the future.

JAD ABUMRAD: (Laughter) Exactly. The story comes...

ROBERT KRULWICH: Does that make any sense? I don't know.

JAD ABUMRAD: Well, it will.

ROBERT KRULWICH: OK, it will.

JAD ABUMRAD: It will. The story comes in two parts, both from our producer Latif Nasser. And here's Part 1.

LATIF NASSER: So the way the story goes, it starts in 1928.

(SOUNDBITE OF MUSIC)

MARYN MCKENNA: 1928, Alexander Fleming, the story goes - who knows if it's apocryphal or not - is growing staph, staphylococcus in his lab.

LATIF NASSER: 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 NASSER: So it likes to be just up our noses or...

MARYN MCKENNA: ...On our genitals or in our armpits, places like that.

LATIF NASSER: 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...

(SOUNDBITE OF MUSIC)

MARYN MCKENNA: ...Potentially deadly.

LATIF NASSER: Anyway, London, 1928...

(SOUNDBITE OF MUSIC)

MARYN MCKENNA: Fleming is growing staph in his lab...

LATIF NASSER: ...In these little petri dishes. And he was a slob, basically.

MARYN MCKENNA: (Laughter).

LATIF NASSER: 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 NASSER: 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 NASSER: ...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 NASSER: I mean, you'd imagine that he would cede some real lush, nice, furry...

JAD ABUMRAD: (Laughter).

LATIF NASSER: ...Lawn of staph just overflowing...

JAD ABUMRAD: Yeah.

LATIF NASSER: ...Right out of the plate.

JAD ABUMRAD: Because it's been sitting there for so long. 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 NASSER: Little patches where the staph is dead.

ROBERT KRULWICH: Dead patches.

JAD ABUMRAD: Dead zones.

ROBERT KRULWICH: So something blew through the window, landed in the dish and starts killing the bacteria.

LATIF NASSER: 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 ABUMRAD: Oh.

ROBERT KRULWICH: Of mold.

MARYN MCKENNA: And they realize that that mold is expressing a compound that is killing the staph around it.

LATIF NASSER: It's, like, emanating rays of death.

JAD ABUMRAD: What was the compound?

LATIF NASSER: That compound was called...

(SOUNDBITE OF CHOIR SINGING)

MARYN MCKENNA: Penicillin.

LATIF NASSER: 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 ABUMRAD: And it just blew in through the window?

MARYN MCKENNA: That is the story that's always been told.

LATIF NASSER: However it got there, it was amazing. It was a miracle.

ROBERT KRULWICH: It was called a miracle drug, right?

MARYN MCKENNA: I mean, it was just - it was - it really was a moment when the world changed. When Fleming was put on the cover of Time magazine...

LATIF NASSER: This was 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.

(SOUNDBITE OF CHOIR SINGING)

LATIF NASSER: But - and this is - I had no idea about this. Virtually at the exact same time when Flemming'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 ABUMRAD: Really?

LATIF NASSER: Yeah.

JAD ABUMRAD: This is happening while he's on the cover?

LATIF NASSER: 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: So almost like...

JAD ABUMRAD: This is our producer Soren Wheeler.

SOREN WHEELER: ...The era of penicillin was over before it began.

MARYN MCKENNA: Almost before it began.

LATIF NASSER: Before it's even released to the general public.

SOREN WHEELER: Wow.

MARYN MCKENNA: And that penicillin-resistant staph moves across the globe.

(SOUNDBITE OF MUSIC)

LATIF NASSER: And in 1957, in Cleveland, some scientists gathered together...

MARYN MCKENNA: ...And they are in a panic. They have no idea why they've lost the antibiotic miracle so quickly.

LATIF NASSER: 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 NASSER: And in 1960, they get it.

MARYN MCKENNA: Methicillin.

(SOUNDBITE OF CHOIR SINGING)

LATIF NASSER: And it works...

MARYN MCKENNA: ...For about 11 months.

SOREN WHEELER: Eleven months?

JAD ABUMRAD: Whoa.

LATIF NASSER: And so we started this arms race.

MARYN MCKENNA: There was a bug, and then there was a drug that took care of it. And then there was a better bug.

SOREN WHEELER: Drug bug, drug bug.

MARYN MCKENNA: Right, exactly.

LATIF NASSER: I actually found this list. Do you want to hear it?

JAD ABUMRAD: Yeah.

LATIF NASSER: OK, so streptomycin - 1943. Resistance - 1948. Methicillin - 1960, resistance - 1961. Clindamycin - 1969, resistance - 1970.

SOREN WHEELER: Wow.

MARYN MCKENNA: You can think of it as leapfrog, or you can think of it as a game of whack-a-mole.

LATIF NASSER: Ampicillin - 1961, then 1973 so that's a little. Carbenicillin - released 1964, resistance - 1974.

JAD ABUMRAD: 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 NASSER: 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 NASSER: And the - and I have on this list is linezolid, which is introduced 2000, resistance 2002.

SOREN WHEELER: Wow.

LATIF NASSER: 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 WHEELER: Why?

MARYN MCKENNA: Well, it takes 10 years and a billion dollars to get to the point where the drug is marketable.

LATIF NASSER: But as soon as you get the drug on the market...

MARYN MCKENNA: ...The resistance clock is running.

LATIF NASSER: So you probably won't make your money back. And as you've probably heard, we now have these situations...

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED REPORTER: A frightening new warning from the Centers for Disease Control about the spread of a string of germs...

MARYN MCKENNA: ...Where literally nothing works...

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED REPORTER: So-called superbugs are now turning up in hospitals.

MARYN MCKENNA: ...And the patient dies.

LATIF NASSER: There are now bugs that can resist all of our drugs.

MARYN MCKENNA: I have seen physicians break down weeping over this. It's not the way that medicine is supposed to fail anymore, but it does.

SOREN WHEELER: I mean, I know that possibly the origin story of penicillin is apocryphal. So this is all a little suspect. But, you know, just to enjoy imaginings for a moment, like, it just seems like if that happened, well, let's just open up a bunch more windows. Something ought to blow in.

MARYN MCKENNA: But we could wait a long time, right? I mean, we had - staph had been around...

LATIF NASSER: Right.

MARYN MCKENNA: ...For millennia before 1928.

LATIF NASSER: Well, actually, there is this story about these two women who did open a window...

(SOUNDBITE OF MUSIC)

LATIF NASSER: ...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 story about a friendship. OK, so you have...

CHRISTINA LEE: Hello. I'm Dr. Christina Lee.

LATIF NASSER: ...Christina.

CHRISTINA LEE: ...And I'm an associate professor in Viking studies at the School of English at the University of Nottingham.

LATIF NASSER: She's a historian. And then you also have...

FREYA HARRISON: Hi, I'm Freya Harrison.

LATIF NASSER: ...Freya.

FREYA HARRISON: I'm a research fellow in the Center for Biomolecular Sciences at the University of Nottingham.

LATIF NASSER: And Freya - Freya's a microbiologist. She studies bacteria. We'll start with her.

FREYA HARRISON: OK. So most of my work is about sort of looking at how bacteria evolve during very, very long-lived infections. But...

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED PERSON: (As Viking) Oh.

FREYA HARRISON: ...My big hobby is Anglo-Saxon Viking reenactment.

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED PERSON: (As Viking) Hold.

FREYA HARRISON: So I'm not purely sort of amateur interest in the history and mainly in dressing up as a warrior and going to fight club every Wednesday night and learning to use the weapons.

ROBERT KRULWICH: Really (laughter)?

FREYA HARRISON: Yeah.

LATIF NASSER: 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, spears, axes. And we give each other a jolly good bashing and have a good time (laughter).

Well, it was really a nice sort of coincidence, really. So I...

LATIF NASSER: So 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 U.K., not only for microbiology, but for Anglo-Saxon and Viking history.

LATIF NASSER: And she goes there to study microbes. But she figured, 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 NASSER: But she figured, hey, 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 is Old English reading group.

LATIF NASSER: That's where she met Christina...

CHRISTINA LEE: Yes.

LATIF NASSER: ...The historian.

CHRISTINA LEE: And I thought Freya was...

LATIF NASSER: At one point, Christine of 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 NASSER: 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 find any kind of friends in my department.

LATIF NASSER: 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 KRULWICH: Is it B-A-L-D?

CHRISTINA LEE: It is indeed.

ROBERT KRULWICH: And leech, like leech, like a leech, like a little worm that grabs onto your - and sucks your blood?

CHRISTINA LEE: No. No, it comes from the Old English word laece (ph), which is actually a healer or a doctor.

FREYA HARRISON: So it's that the little squiggly animals are called leeches because they're medicinal, not the other way around.

ROBERT KRULWICH: Oh.

LATIF NASSER: So the doctor wasn't named for the leech; the leech was named for the doctor.

FREYA HARRISON: Exactly, yeah.

JAD ABUMRAD: 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 ABUMRAD: And what is this book?

LATIF NASSER: So it's kind of 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 NASSER: Locked away.

FREYA HARRISON: But 21st century, very kind people have digitized the original Old English text and put it online.

LATIF NASSER: 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 staph that is a little bit different.

FREYA HARRISON: You know, things like...

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED PERSON: (Speaking Old English, reading).

FREYA HARRISON: ...Possession by the devil.

LATIF NASSER: Which according this leechbook, the remedy for someone who is possessed by the devil is you...

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED PERSON: (Speaking Old English, reading).

LATIF NASSER: ...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...

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED PERSON: (Speaking Old English, reading).

CHRISTINA LEE: How shall we say, make your husband more physically attentive...

LATIF NASSER: (Laughter).

CHRISTINA LEE: ...Or less physically attentive, whichever you - whichever direction you need to moderate it.

ROBERT KRULWICH: Pig's blood, I hope, or toad blood.

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED PERSON: (Speaking Old English, reading).

LATIF NASSER: Actually, it's just you boil a plant in some water and give it to the guy.

ROBERT KRULWICH: Oh.

LATIF NASSER: Yeah.

(SOUNDBITE OF MUSIC)

LATIF NASSER: So Freya and Christina are going through this leechbook looking for some kind of wound...

FREYA HARRISON: Something that was clearly an infection.

LATIF NASSER: ...Some pus-y (ph) something.

FREYA HARRISON: We could clearly say that's bacterial.

LATIF NASSER: And eventually, they find an entry...

FREYA HARRISON: Where at the end of the recipe, it says in Old English...

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED PERSON: (Old English spoken, reading).

FREYA HARRISON: (Speaking Old English) - the best medicine.

LATIF NASSER: The best medicine. Yeah, move over, laughter.

FREYA HARRISON: Yeah, and we thought how can we not try this one?

JAD ABUMRAD: 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 wen (ph) in Old English.

FREYA HARRISON: Yeah. Of course, that could be something like a wart, right? But there is a suggestion by archaeologists that eye infection was rife amongst the Anglo-Saxons...

LATIF NASSER: Really?

FREYA HARRISON: ...Because you lived in buildings where you had smoke going on. You lived crammed together. So it could also be a sty.

JAD ABUMRAD: What is a sty?

FREYA HARRISON: It's an infection of an eyelash follicle.

ROBERT KRULWICH: You rub it, and it itches, and then it gets...

FREYA HARRISON: Yeah.

ROBERT KRULWICH: ...Swollen.

FREYA HARRISON: And it causes quite a nasty red lump.

ROBERT KRULWICH: It's a sty in your eye.

LATIF NASSER: 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 NASSER: ...Staph.

JAD ABUMRAD: Oh, the same stuff is the Mr. Window Man, Penicillin man.

LATIF NASSER: Exactly.

FREYA HARRISON: And we just thought, wouldn't it be nice to have a bit of spare time and had a couple hundred quid to buy the ingredients and just give this a go?

(SOUNDBITE OF MUSIC)

CHRISTINA LEE: Yes, let's give it a try.

FREYA HARRISON: You know, why the hell not?

LATIF NASSER: And matter of fact...

Look at this place.

...We thought that, too.

MATT KIELTY: ...Studio.

LATIF NASSER: Recently, producer Matt Kielty and I went to my tiny apartment in the city, and...

MATT KIELTY: All right.

LATIF NASSER: ...We tried to cook it up, too.

MATT KIELTY: Are you ready to cook?

LATIF NASSER: Oh, I'm ready to cook.

FREYA HARRISON: I've got this recipe here if...

LATIF NASSER: Oh, awesome, yeah.

FREYA HARRISON: ...You'd like it.

LATIF NASSER: Yeah, yeah. Please read it. Go for it.

FREYA HARRISON: OK, it goes like this.

UNIDENTIFIED PERSON: (Speaking Old English, reading).

LATIF NASSER: 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 (speaking Old English) - Christina said it was quite difficult to translate.

CHRISTINA LEE: Nobody quite knows what it is. But luckily...

LATIF NASSER: Just a couple of words over was a clue...

UNIDENTIFIED PERSON: (Speaking Old English, reading).

LATIF NASSER: ...In a second ingredient.

FREYA HARRISON: Garlic.

CHRISTINA LEE: Which is an allium species. And (speaking Old English)...

FREYA HARRISON: We know this was another allium. That's what the Dictionary of Old English tells us.

LATIF NASSER: 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, OK, we'll try one that has onion and one that has leek.

UNIDENTIFIED PERSON: (Speaking Old English, reading).

LATIF NASSER: Now, the recipe doesn't cover this, but we did it anyway. Peel the onion. Chop it up. The same for the garlic.

CHRISTINA LEE: And the recipe, it doesn't tell you how much. It just tells you equal amounts of.

LATIF NASSER: So you take out the measuring cups. You measure out equal amounts.

MATT KIELTY: Yeah, equal amounts into the pestle.

LATIF NASSER: And then after that...

MATT KIELTY: OK, it says...

UNIDENTIFIED PERSON: (Speaking Old English, reading).

MATT KIELTY: ...Pounded well together. OK.

CHRISTINA LEE: You have to really pound it. And pound it, Freya did.

FREYA HARRISON: Yeah, yeah. So lots of time with the mortar and pestle and muscles built up from wielding a sword for pounding the ingredients.

MATT KIELTY: Look, it's starting to be more of a mush.

LATIF NASSER: Third ingredient.

FREYA HARRISON: The next one was definitely something you wouldn't have knocking around in your kitchen.

UNIDENTIFIED PERSON: (Speaking Old English, reading).

FREYA HARRISON: Ox gall.

LATIF NASSER: Ox gall.

FREYA HARRISON: Bovine bile from a cow's gall bladder.

ROBERT KRULWICH: What do you do? You have to kill the cow and then go reaching...

FREYA HARRISON: No, it's actually very standard ingredient in microbiology labs.

MATT KIELTY: Ox bile.

LATIF NASSER: You can but should not just buy it on the internet.

(SOUNDBITE OF MUSIC)

MATT KIELTY: Here we go. Here we go.

LATIF NASSER: And so you take the ox bile, add it to the onion and garlic...

FREYA HARRISON: And then the fourth ingredient...

UNIDENTIFIED PERSON: (Speaking Old English, reading).

FREYA HARRISON: Wine.

LATIF NASSER: It's wine time. Red wine? White wine? Like, what kind...

FREYA HARRISON: Well...

LATIF NASSER: ...Of wine are we talking about here?

FREYA HARRISON: 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 detective work.

LATIF NASSER: 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 NASSER: So they used that wine.

(Non-English language spoken).

MATT KIELTY: (Non-English language spoken).

LATIF NASSER: I just want to point out how difficult it is to find English wine. We had to use Italian. But...

UNIDENTIFIED PERSON: (Speaking Old English, reading).

LATIF NASSER: ...Once you get all that stuff together, you're on to 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 (laughter). So we have to sort of add pieces of - you know, of copper that would have been available to people at the time.

LATIF NASSER: 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 to standard in plumbing fittings.

MATT KIELTY: Dropped a few pennies in there.

LATIF NASSER: We actually used pennies.

MATT KIELTY: Do I stir it? I think I stir it. This is like the world's worst cooking show.

LATIF NASSER: (Laughter).

FREYA HARRISON: It looks and smells like quite a nice summer soup (laughter).

LATIF NASSER: Oh.

MATT KIELTY: Oh, it looks awful.

LATIF NASSER: Oh, that's so gross.

Clearly, we botched this whole thing.

UNIDENTIFIED PERSON: (Speaking Old English, reading).

LATIF NASSER: And finally...

MATT KIELTY: All right. So we're going to cover it.

LATIF NASSER: OK. We're covering it.

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.

(SOUNDBITE OF MUSIC)

MATT KIELTY: OK.

LATIF NASSER: OK. That's it.

ROBERT KRULWICH: One day goes by - two days, three, four, five.

MATT KIELTY: Six, seven, eight, nine.

All right. Nine days later.

LATIF NASSER: All right. Here we go. You ready?

MATT KIELTY: Mmm hmm.

LATIF NASSER: All right. Here we go.

FREYA HARRISON: And...

UNIDENTIFIED PERSON: (Speaking Old English, reading).

FREYA HARRISON: Then you have to strain it through a cloth. The liquid that comes off, you apply to the person's eye.

LATIF NASSER: Oh, the liquid.

UNIDENTIFIED REPORTER: (Speaking Old English, reading).

FREYA HARRISON: Yeah.

CHRISTINA LEE: With a feather, with a feather.

UNIDENTIFIED PERSON: (Speaking Old English, reading).

LATIF NASSER: 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 collagen, so it's a bit like jelly.

LATIF NASSER: Basically, it's 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 NASSER: Then they put this 1,000-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'd - we didn't think this was going to work.

CHRISTINA LEE: No.

FREYA HARRISON: We thought, you know, given the ingredients, we might see some small killing effect on the bacteria, but it won't be anything to write home about.

LATIF NASSER: They thought maybe it'd kill 10%, 20% of the bacteria. But then when they came back the next day...

(SOUNDBITE OF MUSIC)

FREYA HARRISON: It was a staph massacre.

LATIF NASSER: It went on a rampage. It went on a staph rampage.

FREYA HARRISON: It was killing, you know, 99.99999% of these bacterial cells.

LATIF NASSER: What?

FREYA HARRISON: Yeah. First, we thought we'd made some sort of mistake...

LATIF NASSER: (Laughter).

FREYA HARRISON: ...And this was some kind of fluke - you know, we'd accidentally mixed up our plates or mislabeled something.

LATIF NASSER: 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...

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED ACTOR: (As character) Killed them dead.

FREYA HARRISON: ...Wounds.

LATIF NASSER: Then they tried a third time and a fourth and a fifth, and it worked every time.

FREYA HARRISON: And this is just something you really don't see in your career (laughter) as a microbiologist.

LATIF NASSER: And eventually, they escalated from just regular staph to MRSA - to the methicillin-resistant staph. And this is one of the bad ones.

(SOUNDBITE OF MONTAGE)

UNIDENTIFIED REPORTER: A superbug. New government data estimate that about 2,000 people are dying of community-based MRSA every year.

UNIDENTIFIED REPORTER: This one is very dangerous.

LATIF NASSER: 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 NASSER: 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...

UNIDENTIFIED PERSON: (Speaking Old English)

FREYA HARRISON: What the [expletive].

(LAUGHTER)

LATIF NASSER: Bald's best medicine had just wreaked havoc on the MRSA. It killed 90% of them.

FREYA HARRISON: This is - it's beyond our wildest dreams.

LATIF NASSER: Now, Freya and Christina made very clear that this is not yet a miracle drug. I mean, it's not even been tested in humans.

CHRISTINA LEE: So absolutely do not do this at home.

LATIF NASSER: 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 NASSER: So...

MATT KIELTY: We should not have done this (laughter).

LATIF NASSER: Matt and I, we...

(SOUNDBITE OF LIQUID DRAINING)

LATIF NASSER: ...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 use it now, and then it could work. That - the time travel dimension of that is so weird to me.

(SOUNDBITE OF MUSIC)

LATIF NASSER: It kind of makes you think differently about - I don't know - progress.

(SOUNDBITE OF ARCHIVED RECORDING)

UNIDENTIFIED PERSON: So without much further ado, Dr. Christina Lee and Dr. Freya Harrison. And they're going to talk to us about some ancient biotics.

(SOUNDBITE OF APPLAUSE)

LATIF NASSER: For example, just a few weeks ago, Freya and Christina got up in front of the Royal Society of Chemists.

CHRISTINA LEE: Thank you very much, and it is an absolute pleasure to be here.

LATIF NASSER: Large hotel conference room, 100 or so people, Freya actually got up on stage dressed as a nun.

(SOUNDBITE OF ARCHIVED RECORDING)

FREYA HARRISON: OK. So this is one interpretation of what an Anglo-Saxon scientist may have looked like.

LATIF NASSER: And they presented the results.

(SOUNDBITE OF ARCHIVED RECORDING)

FREYA HARRISON: Next ingredient is particularly unpleasant.

LATIF NASSER: They did the cooking demo. And then at some point, Christina said something really interesting. She was like, OK. 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...

(SOUNDBITE OF ARCHIVED RECORDING)

CHRISTINA LEE: There are remedies which ask you, sing four "Ave Marias."

LATIF NASSER: And we would say, oh, that's so superstitious. This is all in their heads.

(SOUNDBITE OF ARCHIVED RECORDING)

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 that's got the watch. Everybody knows the "Ave Maria." Everybody knows the length of an "Ave Maria."

LATIF NASSER: So maybe it's take this medicine and wait 20 minutes. And I know how to standardize 20 minutes, which is...

(SOUNDBITE OF ARCHIVED RECORDING)

CHRISTINA LEE: Three Ave Marias, four Ave Marias.

LATIF NASSER: So in...

ROBERT KRULWICH: Oh, that's fascinating.

LATIF NASSER: It may appear one way. And it, in fact, could be a totally different way.

JAD ABUMRAD: It suggests that the - in order to time travel, you have to somehow - God, it's like we don't even have the language people to be able to understand what they were doing.

LATIF NASSER: There's...

JAD ABUMRAD: And how effective it...

LATIF NASSER: There's a phrase. The past is a foreign country.

(SOUNDBITE OF ARCHIVED RECORDING)

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 NASSER: But here's the reason why this is so confusing to me.

FREYA HARRISON: Mmm.

LATIF NASSER: 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 NASSER: 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 NASSER: How could that even work?

FREYA HARRISON: 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 NASSER: 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 1,000 years, then maybe it wouldn't work.

ROBERT KRULWICH: So there's an interesting discovery there - like, that what worked once and then was resisted, you give it a rest, and it can work again. And 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 paths - you could go to China where they now got all these people studying Chinese cures and Arab cures - you could come up with a rich historical cocktail of armamentarium that will work if you bring them in, take them out, bring them in, take them out. And the whole world of the past then becomes the food of your future, sort of.

SOREN WHEELER: So it's also - like, now I have suddenly an image that it's possible that...

JAD ABUMRAD: This is Soren Wheeler, by the way, in conversation with Maryn McKenna and Latif.

SOREN WHEELER: ...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.

LATIF NASSER: (Laughter).

SOREN WHEELER: And everybody celebrated. And then years later, sties 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, now I'm thinking about future - some future civilization digs up an old medical textbook that was in some dusty whatever and discovers penicillin.

(SOUNDBITE OF HANDEL'S MESSIAH "HALLELUJAH" CHORUS)

SOREN WHEELER: And it works.

(SOUNDBITE OF HANDEL'S MESSIAH "HALLELUJAH" CHORUS)

SOREN WHEELER: 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 seemed like such a great hypothetical construction. I just didn't really know what I could add to it. So...

(LAUGHTER)

SOREN WHEELER: (Laughter) Sorry I took over.

(SOUNDBITE OF HANDEL'S MESSIAH "HALLELUJAH" CHORUS)

UNIDENTIFIED CHOIR: (Singing) Hallelujah, hallelujah, hallelujah, hallelujah.

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