Staph Retreat

Introduction to Radio Lab

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0:20Hey, it's Lulu. This week, I want to bring back an episode about scientists who look in the most unexpected place to find a brand new drug to treat a very tricky bug. The bug is MRSA, that really nasty infection people sometimes get in hospitals, and I don't want to give away the drug because that's sort of all the fun. So I'm going to just pass you off to Jad, Robert, and little baby Latif from about a decade ago. Here we go. Wait, you're listening.

0:50Okay. All right. Okay. All right. You're listening to Radiolab. Radiolab. From WNYC.

1:05Rewind.

Alexander Fleming Story

1:08So the way the story goes, it starts in 1928. 1928. Alexander Fleming, the story goes, who knows if it's apocryphal or not, is growing staph, Staphylococcus, in his lab. That's Maren McKenna. She's a science writer. And staph is a bacterium. It lives on our skin, and it especially likes parts of the body that are warm and damp. So it likes to be just up our noses or... In our genitals or in our armpits, places like that.

1:39And 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... Staph goes from being this benign companion to being potentially deadly. Anyway, London, 1928. Fleming is growing staph in his lab. In these little Petri dishes. And he was a slob, basically. And he goes on a vacation, leaves his Petri dishes covered in bacteria just around, leaves

2:15his window open. And something blows across his lab plates. Some tiny little speck of a thing just floats in through the window and comes to a rest on one of those Petri dishes. And so a few weeks later... Fleming, finally, back from vacation. He needs to use those lab plates again, and he and his assistant go to clean them off. I mean, you'd imagine that he would see some real, lush, nice, furry lawn of staph just overflowing right out of the plate.

2:46Because it's been sitting there for so long. It's been a staph party. 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. Little patches where the staph is dead. Dead patches. So something blew through the window, landed in the dish, and starts killing the bacteria. 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...

3:17Tiny speck of natural mold. Of mold. And they realize that that mold is expressing a compound that is killing the staph around it. It's like emanating rays of death. What was the compound? That compound was called... Penicillin. The first true antibiotic. Infectious diseases that had been killing people for as long as we had been people suddenly could be stopped. And it just blew in through the window? That is the story that's always been told. However it got there, it was amazing.

3:50It was a miracle. It was called a miracle drug, right? I mean, it was just... It really was a moment when the world changed. When Fleming was put on the cover of Time magazine. This was 1944, height of World War II. It was a picture of his face, and the banner on the cover said, His penicillin will save more lives than war can spend. But, and this is, I had no idea about this.

Penicillin Resistance

4:23Virtually 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. Really? Yeah. This is happening while he's on the cover? Virtually the exact same moment. And it's the first sign that staph has responded to the penicillin in the world by developing resistance. It's almost like, uh... Set producer Soren Wheeler.

4:54The era of penicillin was over before it began. Almost before it began. Before it's even released to the general public. Wow. And that penicillin-resistant staph moves across the globe. And in 1957, in Cleveland, some scientists gather together. And they are in a panic. They have no idea why they've lost the antibiotic miracle so quickly. So scientists across the globe put their brains together and try to come up with a new drug. The next amazing thing. And in 1960, they get it.

5:25Methicillin. And it works. For about 11 months. 11 months? Wow. And so we started this arms race. There was a bug. And then there was a drug that took care of it. And then there was a better bug. Drug bug. Drug bug. Right, exactly. I actually found this list. Do you want to hear it? Yeah. Uh, okay, so streptomycin, 1943, resistance, 1948. Methicillin, 1960, resistance, 1961. Clindamycin, 1969, resistance, 1970.

5:57Wow. You can think of it as leapfrog, or you can think of it as a game of whack-a-mole. Ampicillin, 1961, then 1973. So that's a little. Carbenicillin, released 1964, resistance, 1974. They're getting better. They're getting better. There were always more drugs. You know, the drug development was doing really well for a really long time. Hyperacillin, introduced 1980, resistance, 1981. But after the year 2000, drug companies begin to realize it's not really in their best interest to make antibiotics anymore.

6:27And the end I have on this list is Linuzolid, which is introduced 2000, resistance 2002. Wow. There are a few more, but you get the idea. Antibiotic approvals, the entry of new drugs to the market, just kind of fell off a cliff. Why? Well, it takes 10 years and a billion dollars to get to the point where the drug is marketable. But as soon as you get the drug on the market... The resistance clock is running. So you probably won't make your money back. And as you've probably heard, we now have these situations...

6:58A frightening new warning from the Centers for Disease Control about the spread of a string of germs... ...where literally nothing works. ...so-called superbugs are now turning up in hospitals... ...and the patient dies. There are now bugs that can resist all of our drugs. I have seen physicians break down weeping over this. It's not the way that medicine is supposed to fail anymore, but it does. I mean, I know that possibly the origin story of penicillin is apocryphal, so this is all a little suspect.

New Window of Opportunity

7:30But, you know, just to enjoy imaginings for a moment, like, it just seems like if that happened, let's just open up a bunch more windows. Something ought to blow in. But we could wait a long time, right? I mean, staff had been around for millennia before 1928.

7:47But, you know, the whole reason that I wanted to do this story is because kind of there is a new window. It's a different kind of window, though. Not a window next to some petri dishes? Not a window next to some petri dishes. Kind of a window next to some petri dishes, but a totally different kind of window. What kind of window is it? Well, I'm about to tell you that. Is something blowing to the window? Yeah, but it's not mold. It's way more fun than mold. It carries an axe. How about that? So it's a person. Maybe.

8:17I don't even know what I'm referring to anymore.

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9:44Or visit an AT&T store for details.

9:48This is Ira Glass of This American Life. Do you know our show? Okay. Well, either way, I'm going to tell you about it. We make stories. Old-fashioned stories that hopefully pull you in at the beginning with funny moments and feelings and people in surprising situations. And then you just want to find out what is going to happen and cannot stop listening. That's right. I'm talking about stories that make you miss appointments and ignore your loved ones. This American Life, every week, wherever you get your podcasts. Uh, part two?

10:21Yeah. Okay. Hey, I'm Jed Iboomrod. I'm Robert Krolwich. This is Radiolab. We're ready now for part two. Now, remember when part one ended, there was a window open and something was going to come through. We don't know what. We know it's not mold. Yeah, we know it's not mold. So whatever it is, whatever it was, whatever it will be, we will hear about it now from our reporter, Lattif Nasser.

Bald's Leech Book

10:40Well, 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 story about a friendship. Hey, everybody. Hello again. Hello again. It's a buddy film. It's a buddy. Yeah, it's a buddy movie. Okay, so yeah, maybe just walk us through it. Right. So, okay, so you have... Hello, I'm Dr. Christina Lee. Christina. And I'm an associate professor in Viking studies at the School of English at the University

11:16of Nottingham. She's a historian. And then you also have... Hi, I'm Freya Harrison. Freya. I'm a research fellow in the Center for Biomolecular Sciences at the University of Nottingham. And Freya's a microbiologist. She studies bacteria. We'll start with her. Okay. So most of my work is about sort of looking at how bacteria evolve during very, very long-lived infections. But my big hobby is Anglo-Saxon and Viking reenactment.

11:46So I had 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. Really? 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. Everything from swords, spears, axes. And we give each other a jolly good bashing and have a good time.

12:16I only mention this because it actually plays into the story. Well, it was a really nice sort of coincidence, really. 2012. A few years after finishing her doctorate, Freya goes off to work at the University of Nottingham. Nottingham's one of the places in the UK not only for microbiology, but for sort of Anglo-Saxon and Viking history. And she goes there to study microbes, but she figures, hey, why not, while I'm here, brush up on my old English?

12:49I'd studied some old English to a level where I could sort of read and speak a little bit.

12:56But she figured, hey, she could be better. And if she did, she would get deeper into the whole reenactment thing. So I rather cheekily emailed the School of English's old English reading group. That's where she met Christina. Yes. The historian. 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. I just kind of thought, I've found my kindred spirit here.

13:28Because 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. I've been interested in infectious disease for quite a long time, which I don't find any kind of friends in my department. She told me she's the kind of person who would, you know, watch Ebola coverage on the news and not be able to stop watching. So eventually they start talking about historical diseases. So, like, how would people back then have treated something like, you know, Ebola?

14:01Freya 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. It's known as Bald's Leech Book. So this is about 1100 years old. What's it called? Bald's what? Bald's Leech Book. It's nothing to do with no hair. Oh. Even though it is spelled. Bald, is it B-A-L-D?

14:32It is indeed. And leech, like a leech, like a little worm that grabs onto your blood? No, no, it comes from the old English word lecher, which is actually a healer or a doctor. So the little squiggly animals are called leeches because they're medicinal, not the other way around. Oh. So the doctor wasn't named for the leech, the leech was named for the doctor. Exactly, yeah. And Bald is a man, the guy who wrote the book? We think it's a guy, we think it's a guy's name. And what is this book? So it's kind of like this old healer's handbook. It's filled with these potions and cures.

15:03The original manuscript is in the British Library. Locked away. But 21st century, very kind people have digitized the original old English text and put it online. So Christina and Freya bring it up and they start going through all the remedies. And, you know, it describes to you remedies for stuff that is a little bit different. You know, things like... Thone devil. Thone manon. A possession by the devil. Which, according to this leech book, the remedy for someone who's possessed by the devil is you... Spew a drink. And lutre.

15:33Make this kind of like foul brew. You make them drink it and it'll make them vomit out the devil. And then there's another remedy for warts. Bishé ob wirt ek nua to somne. And all I'm going to say about that one is that it involves hound's urine and mouse blood. And then things like... Yif man seya torana. How should we say, make your husband more physically attentive? Or less physically attentive, whichever you, whichever direction you need to moderate it. Pig's blood, I hope.

16:04Or toad blood. Drink on neacht nestia. Actually, it's just you boil a plant in some water and give it to the guy. Oh. Yeah. Anyway. So Frey and Christina are going through this leech book, looking for some kind of wound. Something that was clearly an infection. Some pussy, uh, something. Something we could clearly say that's bacterial. And eventually they find an entry... Where at the end of the recipe, it says in Old English... Se besta lachedom. Se besta lachedom.

16:35The best medicine. The best medicine. Hmm. Yeah, move over laughter. Yeah. And we thought, how can we not try this one? What was the best medicine for? So it said it was for a lump in the eye. It's actually called wen in Old English. Yeah. These days if you get a... Of course that could be something like a wart, right? Mm-hmm. But there is a suggestion by archaeologists that eye infection was rife amongst the Anglo-Saxons because you lived in buildings where you had smoke going on, you lived cramped together.

17:08So it could also be a stye. What is a stye? It's an infection of an eyelash follicle. You rub it and it itches and then it gets swollen. Yeah, and it causes quite a nasty red lump. It's a stye in your eye. Stye in your eye. Now it just so happens that the bacteria that causes the stye in your eye is... Staphylococcus aureus. Staph. Oh, the same stuff as the Mr. Window Man, penicillin man. Exactly. And we just thought, wouldn't it be nice to have a bit of spare time and earn a couple of hundred quid to buy the ingredients and just give this a go?

17:38Yes! Let's give it a try. You know, why the hell not? And, matter of fact... Look at this place! We thought that too. Studio. Not bad at all. Recently, producer Matt Kielty and I went to my tiny apartment in the city and we tried to cook it up too. Are you ready to cook? Oh, I'm ready to cook. I've got this recipe here if you'd like it. Oh, awesome. Yeah, yeah, yeah. Please read it. Go for it. Okay. It goes like this.

18:08That's the first line of the recipe. And right off the bat, for Christina and Freya, there's a problem. That first ingredient... The word cropliach. Cropliach. Cropliach. Christina said it was quite difficult to translate. Nobody quite knows you know what it is. But luckily... Just a couple words over was a clue. And garliach. The second ingredient... Garlic, which is an allium species. And cropliach. We know this was another allium. That's what the Dictionary of Old English tells us. So they figured probably what they were dealing with was an onion or a leek. But we didn't know which one. So we thought, okay, we'll try one that has onion and one that has leek.

18:43Now, the recipe doesn't call for this, but we did it anyway. Peel the onion. Chop it up. The same for the garlic. And the recipe, it doesn't tell you how much. It does tell you equal amounts of. So you take out the measuring cups. You measure out equal amounts. Yeah, equal amounts. Into the pestle. And then after that... Okay, it says... A canoea well. Did it be? To somne. Pounded well together. Okay. But you have to be really pounded. And pounded Freya did.

19:14Yeah, yeah. So lots of time with a mortar and pestle. Muscles built up from wielding a sword for pounding the ingredients. Look, it's starting to be more of a mush. Third ingredient? The next one was definitely something you wouldn't have knocking around in your kitchen.

19:31Ox gall. Ox gall. Bovine bile from a cow's gallbladder. What, do you have to kill the cow and then go reach it? No, it's actually a very standard ingredient in microbiology labs. Ox bile. Today in 2015, you can but should not just buy it on the internet. Here we go, here we go. And so you take the ox bile, add it to the onion and garlic. And then the fourth ingredient? Wine.

19:52Wine time. Red wine, white wine. And what kind of wine are we talking about here? 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. And she figured out that the monastery where this leech book was written, well, she figured out where their vineyard was. And just down the road, there's this modern organic vineyard. So they used that wine. I just want to point out how difficult it is to find English wine. We had to use Italian.

20:23But once you get all that stuff together, you're under the final ingredient. The fifth ingredient was actually that you're specifically told that you have to mix these ingredients together in a brass or a bronze pot. I don't have one. So we had to sort of add pieces of copper that would have been available to people at the time. 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 cartridge brass,

20:53which is what's used as standard in plumbing fittings. Dropped a few pennies in there. We actually use pennies. Do I stir it? I think I'd stir it. It's like a world's worst cooking show. It looks and smells like quite a nice summer soup. Oh. Oh, that looks awful. Oh, that's so gross. Clearly we botched this whole thing. Let us stand the neon nicked on the other fatter. And finally... So we're going to cover it. Okay, we're covering it. The directions say we have to let the whole thing sit for a while. It has to be stored for nine days and nights.

21:25One day goes by two days, three, four, five, six, seven, eight, nine. All right. Nine days later. All right, here we go. You ready? Mm-hmm. All right, here we go.

21:44And... Then you have to strain it through a cloth. The liquid that comes off, you apply to the person's eye. Oh, the liquid. And um nicked, though, mid-feather. Yeah. With a feather. With a feather. Se bet's the latchet on. Now, clearly we didn't have any staff to try this out on, but Freya, in her lab, she made these mock wounds. With these little plugs of collagen, so it's a bit like jelly. Basically, it's like a goopy substance made to be kind of like a flesh wound.

22:16And we infect these wounds with bacteria, with the staff. 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. Obviously, we didn't think this was going to work. No. 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. They thought maybe it'd kill 10%, 20% of the bacteria. But then when they came back the next day... It was a staff massacre. It went on a rampage.

22:47It went on a staff rampage. It was killing, you know, 99.99999% of these bacterial cells. Yeah. First, we thought we'd made some sort of mistake, and this was some kind of fluke. You know, we'd accidentally mixed up our plates or mislabeled something. So, they run the entire experiment again. They grab the ingredients, mash them up, put them on some bacteria, and it happens again. Just absolutely wiped out the bacteria in these fake wounds. Then they tried a third time, and a fourth, and a fifth, and it works every time.

23:19And this is just something you really don't see in your career as a microbiologist. And eventually, they escalated from just regular staff to MRSA, to the methicillin-resistant staff. And this is one of the bad ones. The superbug. New government data estimate that about 2,000 people are dying of community-based MRSA every year. This one is very dangerous. So, Christina and Freya, they sent some of Bald's brew to one of their collaborators in the states.

23:52Our collaborator, Kendra Rumbaugh, in Lubbock, in Texas. Kendra took the stuff, put it on some MRSA bacteria, and then a week later sent Freya and Christina an email. And I think it was actually a three-word response. I think she just simply said, What the f**k? What the f**k?

24:10Bald's best medicine had just wreaked havoc on the MRSA. It killed 90% of them. This is beyond our wildest dreams. 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. So, absolutely do not do this at home. They don't even know if this is safe. 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. So, uh... We should not have done this.

24:42Matt 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 use it now and then it could work. Like, that...

25:12The time travel dimension of that is so weird to me.

25:20It kind of makes you think differently about... I don't know. Progress. So, without much further ado, Dr. Christina Lee and Dr. Freya Harrison, and they're going to talk to us about some ancient biotics. For example, just a few weeks ago, Freya and Christina got up in front of the Royal Society of Chemists. Thank you very much, and it is an absolute pleasure to be here. Large hotel conference room, 100 or so people.

25:50Freya actually got up on stage dressed as a nun. Okay, so this is one interpretation of what an Anglo-Saxon scientist may have looked like. And they presented the results. Next ingredient is particularly... 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... There are remedies which ask you, sing for Ave Maria's.

26:24And we would say, oh, that's so superstitious. This is all in their heads. 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. So maybe it's take this medicine and wait 20 minutes, and I know how to standardize 20 minutes, which is... Three Ave Maria's, four Ave Maria's may actually be time. That's fascinating. It may appear one way, and it, in fact, could be a totally different way.

26:55It 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 and how effective it was. There's a phrase, the past is a foreign country.

27:10We 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, still from them. I learned a bit of humility this way. But here's the reason why this is so confusing to me. So 1,100 years is a crazy long time for humans, and for bacteria, that's like an exponentially crazy long time.

27:41Yeah. So how is it that something that this man bald was doing to these bacteria then, like it's not even the same bacteria? Yeah. How could that even work? 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, 1,000 years later, when these medicines have not been used, you would expect that resistance to be lost.

28:13This is something that Maren McKenna mentioned to Soren and I, that sometimes when you take a drug out of circulation... 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. 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.

28:44And you put it to rest, and if you had enough different, if you could go to different places in the different paths, to 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 armamentariums that will work if you bring them in, take them out, bring them in, take them out. And the whole world, the whole world of the past then becomes the fruit of your future, sort of.

29:13So it's also possible, like now I have suddenly an image that it's possible that... This is Soren Wheeler, by the way, in conversation with Maren McKenna, Latif. That 1,000 years ago, these folks went through what we went through with penicillin, in that 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. He got their Nobel Prize. 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.

29:45And then here we are, and we discover it, and it's been put away long enough that... Like, now I'm thinking about some future civilization digs up an old medical textbook that was in some dusty whatever and discovers penicillin. And it works.

30:02Did I lose you on that, Maren? 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.

30:13Sorry I took over. Hey, Lulu again, with a quick update.

Update on Bald's Eye Salve

30:25It has been almost a decade since we first aired this episode, and since then, Christina and Freya have published several papers to show how this concoction works and why. Now, Bald's eye salve is not quite ready to hit the drugstore shelves yet, but in 2022, it made it over a big hurdle for new drugs, phase one safety trials. It was tested on healthy humans, so not already sick folks, and not in open wounds, and the results were overall successful. And Freya and her colleagues have a pretty good idea now of which chemicals in the medicine are the important ones so they can distill it down to its bacteria-fighting essence.

31:00It's potentially great news for all of us staying a little healthier using very old things. But all this, you know, it did leave me with one very important question for Christina, the Viking expert. If we get further in clinical trials, and this actually becomes, you know, a drug, who owns the patent? Is it Mr. Bald or whoever from like a thousand years ago? So we asked Christina, the Viking expert. I don't know.

31:31I've not, you know, I really don't know, but, you know, technically, Mr. Bald is having this manuscript written for him. It's in his possession, but that doesn't mean it's his work. So it becomes a really interesting question, you know, of who owns the IP on this. Anyway, Radiolab, here for you, the hard-hitting medical questions, the hard-hitting patent questions. Thanks so much for listening.

32:02We'll be back next week. Special thanks this hour to Steve Diggle. And to Alexandra Ryder and Justin Park, who came down from Yale to be our old English readers. To Gene Murrow from the Gotham Early music scene. And to Marsha Young on the Medieval Harp. Colin Monroe of Tadcaster. And the rest of the Barony of Iron Bog. Not totally sure what that is, but I know they helped us out. And I guess we should help ourselves out. Yes, very quickly. Or through the window. I'm Jed Iwumran. I'm Robert Krulwich. Thanks for listening.

32:41Hi, I'm Gabby. I'm from the Bay Area, California. And here are the staff credits. Radiolab is hosted by Lulu Miller and Latif Nasser. Soron Wheeler is our executive editor. Sarah Sandback is our executive director. Our managing editor is Pat Walters. Dylan Keefe is our director of sound design. Our staff includes Jeremy Bloom, W. Harry Fortuna, David Gable, Maria Paz Gutierrez, Sindhu Nainasambandan, Matt Kielty, Mona Mudgauker, Annie McKeown, Alex Neeson, Sarah Kari, Natalia Ramirez, Rebecca Rand, Anissa Vitsa, Arian Wack, Molly Webster, and Jessica Young.

33:22With help from Gabby Santis. Our fact checkers are Diane Kelly, Emily Krieger, Natalie Middleton, Anjali Mercado, and Sophie Samae. Leadership support for Radiolab's science programming is provided by the Simons Foundation and the John Templeton Foundation. Foundational support for Radiolab was provided by the Alfred P. Sloan Foundation. Radiolab is supported by Capital One.

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