[RADIOLAB INTRO]

LULU MILLER: This is Radiolab. I'm Lulu Miller.

LATIF NASSER: I'm Latif Nasser.

JENN: Oh, hello!

LULU: Along with reporter Jenn Brandel.

LATIF: Hi!

LULU: Latif, Jenn, have you guys met?

JENN: I have not.

LATIF: I don't think so.

JENN: No.

LULU: So Jenn is a radio reporter who I've known for a long time. But these days ...

JENN: I'm a little hard to explain. I have been a journalist. I'm a CEO of a tech company right now.

LATIF: Ooh!

JENN: I work between a few worlds, between entrepreneurship, democracy, media, blah blah blah.

LATIF: Hmm.

JENN: Yeah.

LATIF: Well!

JENN: "Hmm" is right. I'm an annoying person to talk to at a cocktail party because I can't really say it succinctly. I'm not like, "I'm an astronaut. I'm a firefighter."

LATIF: Right.

LULU: And that'll—that'll maybe come back. Okay, so—I don't know. Shall we just—shall we begin? Are you ready for ...

JENN: Yeah!

LULU: Are you ready for a journey?

LATIF: Yeah.

LULU: Okay, so we're gonna just kick it off ...

JENN: Caffeinated, bagels, ready to go.

LULU: We are gonna start inside a hospital on the fourth floor.

ELEVATOR: Fourth floor. Going up.

LULU: Jenn and I are walking around. It's NYU Hospital.

LATIF: Okay.

LULU: We're trailing some doctors. And we're in this part of the hospital I have never thought about that exists but it very much exists.

NEIL THEISE: So this is Lulu, this is Jenn.

JENN: Hi.

LULU: Hi.

NEIL THEISE: They have permission to be here.

LULU: So we walk into this room that looks a little bit like an industrial kitchen.

NEIL THEISE: We just can't mention any identifiers.

LULU: There are big metal counters and sinks. And anyway, these doctors, they're pulling out Tupperwares, and kind of one by one they are lifting the lids and pulling out ...

LULU: Whoa!

LULU: ... human organs.

LULU: Oh!

NEIL THEISE: So that's small intestine coming here.

LULU: Organs I've heard about but never seen before.

NEIL THEISE: And this is the pancreas.

LULU: They pulled out a whole stomach.

LULU: It's just like a big orangey-red chunk of meat.

LULU: And they pulled out ...

NEIL THEISE: Here's the dome of the uterus.

LULU: Oh, wow!

LULU: ... a uterus.

DOCTOR: This is your ovary.

LULU: Whoa!

JENN: Whoa!

LULU: And they pulled out ...

NEIL THEISE: Here's a large fatty red tissue, and that's the breast tissue.

LULU: ... a whole breast. They pulled out ...

LULU: Wow, okay.

LULU: ... a liver.

LULU: A brain?

NEIL THEISE: No, this is skin.

LULU: Just organ after organ.

LATIF: Are these organs for training, or ...?

JENN: No, no, no, no. These are fresh.

JENN: It looks like we're seeing ...

NEIL THEISE: This is your stomach juice.

JENN: ... blood, and ...

LULU: Some of them were dripping blood.

NEIL THEISE: Yeah, there's blood. The red stuff is blood.

LULU: Some were dripping bile.

JENN: These were organs that had come out of people that day.

NEIL THEISE: Oh, so are you on pancreas today?

LULU: And so what this room is is it's the pathology lab, where they are looking at anything that has been taken out of or off of a patient in the hospital.

NEIL THEISE: Coming down from the operating room all day, hundreds of specimens a day.

LULU: Because maybe that person's getting a transplant or maybe they had ...

JENN: And what is that?

NEIL THEISE: Uh, that's cancer.

LULU: ... a tumor removed.

NEIL THEISE: Yeah.

JENN: Wow, that's a big—that's like a tennis ball amount.

NEIL THEISE: Yeah. Now here's ...

LULU: It's, like, dizzying because it's these pieces of people that they hold these—you know someone, like, two floors above you is going through a huge day.

LATIF: Right.

LULU: But the reason why we were there that day was to see a body part.

LULU: Should we just go now?

NEIL THEISE: Yeah.

LULU: Oh, okay.

LULU: A sort of ...

NEIL THEISE: I am giving consent for this procedure.

JENN: I am giving consent ...

LULU: ... organ ...

LULU: I just tested the syringe. A couple drops came out. Here comes the big needle!

LULU: ... inside the human body ...

NEIL THEISE: Ready?

JENN: Mm-hmm.

LULU: ... that scientists had ...

LULU: Whoa!

NEIL THEISE: There it is.

LULU: ... completely missed.

LULU: Is that it? Are we looking at it right now?

NEIL THEISE: That's it.

LULU: Even though it had just been sitting there ...

LULU: Oh my gosh. I'm—wow!

LULU: ... all this time inside of all of us.

LATIF: An organ?

JENN: Yeah.

LULU: Yee—well, a body part.

JENN: A big deal body part.

LULU: A big deal body part.

LATIF: A big deal body part that we'd missed.

LULU: Until, like, five years ago.

LATIF: What?

JENN: [laughs]

LULU: Yeah, and so today ...

LATIF: How could that be?

LULU: Well, that's ...

JENN: Well ... [laughs]

LULU: ... the story we're gonna tell you. How we missed it.

LATIF: No, people have been looking at the human body for—like, since the beginning.

JENN: Yup, exactly. Which is why it's so bizarre that we missed it.

LATIF: I don't even know if I believe you.

JENN: [laughs]

LATIF: I'm, like, in disbelief here.

JENN: As were many.

LULU: Yeah, so we're gonna tell you the story of what this mysterious body part is, what its name is, what it might be doing, why we missed it, how knowing about it might change our lives, our health and maybe even, like, society a little bit.

LATIF: Really?

LULU: But I'm gonna pipe down because Jenn's gonna tell you the rest.

JENN: All right. Oh, great. Now I just had a Google meeting pop up. Let me just kill all these things. Stop it!

LATIF: Okay. Yeah.

LULU: From your 17 other jobs that you work.

JENN: Yeah, exactly. [laughs] Okay. All right, okay. So the story starts with this guy, Neil Theise.

NEIL THEISE: Hello!

JENN: Hey Neil, how are you doing?

JENN: Dr. Neil Theise.

NEIL THEISE: I'm good.

JENN: Okay, let me see ...

JENN: So Neil was actually one of the doctors ...

NEIL THEISE: So this is Lulu, this is Jenn.

JENN: ... who was showing us around the lab.

LATIF: Okay.

JENN: He's a kind of short, muscly fellow, he's got tattoos on his arms. And he's kind of an unlikely doctor because he studied computer science, and he thought he was gonna be a rabbi for part of his life.

NEIL THEISE: So I was sort of all over the map.

LULU: The classic rabbi programmer!

JENN: [laughs]

NEIL THEISE: No, exactly! Exactly. Yeah, yeah, yeah.

JENN: What about—why did you want to become a doctor in the first place?

NEIL THEISE: Hmm.

JENN: Sorry, I know this could be a long story, but quickly. Like, in summation.

NEIL THEISE: I was a freshman in college. I was gay and couldn't cope with it, and I thought—and I'm a child of holocaust survivors too, so my formula was I'm gonna get old, I'll never get married, I'm never gonna have kids and I'll be doing Hitler's job for him because of that. And—and I'm gonna grow old and die alone.

JENN: So when he graduated with degrees in computer science and Jewish studies, he was like, "What am I doing? What is my role in the world?" And then one day ...

NEIL THEISE: My mother called me up and said, "Oh, bad news."

JENN: The doctor that she had worked for and who had delivered him and his brother in his hometown in Connecticut ...

NEIL THEISE: Had died of a heart attack on the golf course that morning, and the funeral was gonna be the next day. So she called me after the funeral, and I said, "How was Dr. Robinson's funeral?" And she said, "It was just amazing. All of Hartford came out for his funeral." And I thought, oh, if you're a doctor, people come to your funeral.

JENN: Hmm.

NEIL THEISE: [laughs] So that's why I went to medical school.

LULU: Wait! Wait, so, like, most people go into medicine because they care about other people—or they say that—but you went because you wanted more people to care about you?

NEIL THEISE: [laughs] Yeah, basically. I was terrified of being alone, and I thought I won't be alone. I'll have meaningful relationships and I'll do good things in the world, and—and my life won't be meaningless.

JENN: So he goes off to med school.

NEIL THEISE: Discovered pathology in the middle of it, and was like, "Oh, I like this."

JENN: Which is funny because in pathology ...

NEIL THEISE: Opening up the small intestine ...

JENN: ... you're mostly dealing with ...

NEIL THEISE: I'm lifting up the lining of the stomach.

JENN: ... the parts of patients, not the actual people themselves.

NEIL THEISE: But I just really loved looking at beautiful puzzles.

JENN: Because a lot of what pathology is ...

NEIL THEISE: So I've got this big stack of slides here.

JENN: ... is taking an organ and making a tiny ...

NEIL THEISE: Cut off a very, very thin slice.

JENN: ... little sample of it, putting it on a slide, adding some stains to it to give it color ...

NEIL THEISE: And then we'll look at it under the microscope.

JENN: Where he'll see ...

NEIL THEISE: A pattern of colors.

LULU: Whoa!

NEIL THEISE: Shapes.

JENN: Oh my God!

NEIL THEISE: Relationships between the shapes.

LULU: Okay. Wow.

NEIL THEISE: So each cell has a particular shade. The magenta stain here is the blood vessel lining cells. Sort of like a stained glass. This is an artery and this is a vein. The teal or greenish color—these white spaces here, and this is fat. And so—see how that looks blue?

LULU: Yeah.

NEIL THEISE: I sit down at my microscope and I look at the slides—I know that's a bad sign—and I make diagnoses.

JENN: So he ends up becoming a liver pathologist, and like a world-renowned one at that. But he's also super accessible and, like, friendly. And even though he's not working directly with patients, he has a lot of meaningful relationships with people. And they go to him for things, like if they're seeing something they've never seen before, which is what happened in 2015.

NEIL THEISE: When I was at Beth Israel Medical Center in New York.

JENN: So he had a—this cush job at Beth Israel.

NEIL THEISE: It was very luxurious. I had my own room with a multi-headed microscope.

JENN: Removed from all the action so he could focus on his microscope all day long.

NEIL THEISE: And ...

JENN: A colleague walks in one day ...

NEIL THEISE: ... David Carr-Locke.

JENN: Um, Neil told us you are a scope jockey?

DAVID CARR-LOCKE: [laughs] He would say that. Do you know what that means?

JENN: Is that a term of art?

DAVID CARR-LOCKE: No, no. It's very, very derogatory.

LULU: Is it like a dig of someone who likes looking in microscopes?

DAVID CARR-LOCKE: No! No, no, no. An endoscope.

LULU: Oh, endoscope. Oh, okay.

DAVID CARR-LOCKE: Yeah.

LULU: They like to put it up the places and look around.

DAVID CARR-LOCKE: Yeah. Or down the places and look around.

JENN: Down and up. Through all the ends.

DAVID CARR-LOCKE: Yes. Very good. That's what I do.

JENN: He's a gastroenterologist.

DAVID CARR-LOCKE: Thank you.

JENN: And so he comes into Neil's office and he's like, "Hey man," No, he's probably more like "Excuse me, Dr. Theise."

DAVID CARR-LOCKE: We've got this new scope.

[ARCHIVE CLIP, advertisement: Until now, gastroenterologists were often in the dark.]

JENN: A very fancy endoscope.

DAVID CARR-LOCKE: It's basically a miniature microscope.

[ARCHIVE CLIP, advertisement: Enabling you to see what you've been missing so far.]

DAVID CARR-LOCKE: So you can see cells in a living person.

[ARCHIVE CLIP, advertisement: With real-time microscopic information critical to their decision-making process.]

DAVID CARR-LOCKE: And it was showing us something that we didn't understand.

LATIF: Hmm.

JENN: In particular, it was showing them something in ...

NEIL THEISE: Bile duct has arrived.

JENN: ... the bile duct.

NEIL THEISE: The bile duct.

JENN: So the bile duct is this tiny, tiny organ.

JENN: So it's like a—just a tube.

JENN: We looked at it with Neil.

JENN: I don't know, three inches long? Two-and-a-half, three inches long.

JENN: It's like a piece of spaghetti? Like a little piece of spaghetti.

LATIF: Oh, wow!

LULU: I'd call it more ziti.

JENN: A dried ziti. A little mini ziti.

LULU: Where—where is the bile duct?

NEIL THEISE: Yeah, it's sort of if you go about three or four inches above your belly button, straight in.

LATIF: And what does the bile duct do again?

JENN: So the bile duct takes bile that your body produces, and it sends it to your small intestine to help with things like digestion and to fight off toxins.

LATIF: Okay.

JENN: So a super important organ.

DAVID CARR-LOCKE: It's purely a passive tube, but it does a lot of important things.

JENN: So when patients come in and have something like abdominal pain or the whites of their eyes are yellow or maybe their skin is itchy ...

DAVID CARR-LOCKE: One of the causes of problems like that is a narrowing in the bile duct, which could be benign or it could be cancerous.

JENN: So the patient gets sent to David's OR.

DAVID CARR-LOCKE: And then we give the patient an injection of something called ...

DAVID CARR-LOCKE: This is fluorescein.

DAVID CARR-LOCKE: ... fluorescein.

JENN: This is actually what the microscope sees, this fluorescent liquid.

DAVID CARR-LOCKE: It will distribute itself through the blood system and fluid spaces within seconds.

JENN: It basically lights up wherever there's fluid in your body. And then after the shot, David grabs his fancy scope.

LULU: So it kind of just looks like a big black hose.

DAVID CARR-LOCKE: It's about as thick as your finger.

LULU: With a flashlight at the end.

JENN: And then ...

LULU: Ah. Bloo bloo bloo.

JENN: ... he threads the scope ...

DAVID CARR-LOCKE: Down the esophagus, past the stomach.

JENN: ... into the small intestine.

DAVID CARR-LOCKE: And into the bile duct.

JENN: So David and his colleague Petros Phineas, they're looking through this new, fancy microscope, and they're seeing something they had never seen before: the walls of the bile duct were glowing.

DAVID CARR-LOCKE: If you could imagine a sort of honeycomb appearance.

JENN: Where they'd always seen just like a dark wall, there now were these glowing holes where the fluorescein was showing, with these little dark fibers around them.

DAVID CARR-LOCKE: In this nice regular honeycomb shape.

LATIF: And this is in patients who have bile ducts that are diseased, or ...?

LULU: No, no, no.

DAVID CARR-LOCKE: In a normal bile duct.

LULU: In a normal, healthy bile duct he was seeing again and again this honeycomb of lit-up holes in the wall.

DAVID CARR-LOCKE: Well, why haven't we seen this before?

JENN: And so David took some pictures of the honeycomb.

DAVID CARR-LOCKE: We went to Neil.

NEIL THEISE: And they show me the pictures.

DAVID CARR-LOCKE: And I said, "Look, what is this thing? What does this correspond to that you've been looking at for the last 30 years?"

NEIL THEISE: And I was like, "I don't know what the hell I'm looking at." [laughs] I just don't know what I'm looking at.

JENN: I mean, Neil says, like, you know, I've looked at the walls of a bile duct under the microscope an uncountable number of times, and ...

NEIL THEISE: There's no spaces there.

JENN: ... it's pretty much solid.

NEIL THEISE: Like a dense wall.

JENN: So he's looking at all these lit-up holes, thinking ...

NEIL THEISE: This doesn't make any sense. Really intense cognitive dissonance.

JENN: Hmm.

NEIL THEISE: Which is a lovely place to be scientifically. You know ...

LULU: For some people.

JENN: [laughs]

NEIL THEISE: Yeah. Well, you know there's some really important piece here that will make sense of it, just what is it and how do you find it out?

JENN: So Neil took these images of the honeycomb.

NEIL THEISE: I couldn't find them in any textbook.

JENN: And he would show them to colleagues on his lunch break.

NEIL THEISE: And people were making fun of me.

JENN: They were like, "Neil? He's just wild about bile."

NEIL THEISE: Right. [laughs]

JENN: People just didn't really care.

NEIL THEISE: Yeah. Yeah. So—so I don't know how long it took.

JENN: But eventually Neil was like, "Wait a second, when David uses his new scope ...

[ARCHIVE CLIP, advertisement: What you've been missing so far.]

JENN: "... he's looking at live tissue. But ...

NEIL THEISE: All the tissue I see is dead. So a specimen comes down from the operating room ...

JENN: So whenever an organ lands on the lab desk of a pathologist ...

NEIL THEISE: You drop it in formaldehyde.

JENN: ... you do all this stuff to it.

NEIL THEISE: And you wash it ...

JENN: Dip it in alcohol.

NEIL THEISE: Put it into wax, because you're mummifying it.

JENN: You're dehydrating it.

NEIL THEISE: You're turning it into a mummy of itself.

JENN: Then you shave off a super-thin slice of it ...

NEIL THEISE: And put it under the microscope.

JENN: Neil showed us a slide of the bile duct, and ...

NEIL THEISE: Now see all these cracks?

LULU: Yeah.

JENN: You see all these faint little cracks in the wall.

NEIL THEISE: We always thought they were cracks.

JENN: Now in medical school, Neil and everybody else was taught that those cracks were caused by the heating and drying process of just making the slide. So for 30 years, he had ignored these cracks, thinking they were just an artifact of the process.

NEIL THEISE: But they're not.

JENN: But after seeing David's pictures of the live tissue and then studying different samples that had been frozen rather than dried out, he realized those cracks ...

NEIL THEISE: They're the remnants of the living spaces.

JENN: They were what was left behind when the holes of this honeycomb dried out and would sort of collapse on itself.

LATIF: Huh!

JENN: It's sort of like have you seen those tiny little sponges that are dehydrated, and then you put them in water and then they go—foom!

LATIF: Like the ones that are shaped like a dinosaur or something?

LULU: The ones that are like a pellet, and then it's like boom, a stegosaurus!

LATIF: Right.

JENN: [laughs] Yeah. So you can think about the way that slides have been being made for, like, a hundred years like the pellet. That's what they've been looking at.

LATIF: Oh!

JENN: But with David's scope, they were seeing the pellet expanded into the sponge form, full of holes, which is how the walls around a real, living, bile duct actually look.

NEIL THEISE: And so we realized bile ducts are not like anything we thought they were.

LATIF: Huh!

LULU: Which, you know ...

NEIL THEISE: Who cares about the bile duct, right?

LULU: Who actually cares that the bile duct is encased in a spongy honeycomb wall?

NEIL THEISE: Big deal. [laughs]

JENN: But this is where it gets interesting.

NEIL THEISE: So within days ...

JENN: Neil is back to doing clinical work.

DAVID CARR-LOCKE: And he started to look at tissues that he sees every day, but now with a new eye.

JENN: So one day, he gets sent a breast.

NEIL THEISE: From a woman who had breast cancer and had to have her breast taken off. And the breast always comes with a portion of the skin.

JENN: So Neil did his thing.

NEIL THEISE: Formaldehyde and alcohol and wax.

JENN: Took some of the healthy skin, put it under the microscope and saw ...

NEIL THEISE: It had the same cracks.

JENN: Hmm.

NEIL THEISE: So that was exciting.

JENN: And it wasn't just the skin. He was seeing those cracks in the collagen around the stomach, around the colon.

NEIL THEISE: There are cracks.

JENN: Tiny little cracks in a dense wall.

NEIL THEISE: It's not just the bile duct. Okay, now that's more interesting. So I called the guys and I showed them and it was like, "Oh, this is really cool!"

DAVID CARR-LOCKE: And Neil, of course, being Neil ...

JENN: Said, "How about we use the fancy endoscope ...

DAVID CARR-LOCKE: On him.

JENN: "... to see if the places where you're usually seeing cracks might also—not dried out—have this network of fluid-filled holes?"

NEIL THEISE: "Do it on me."

DAVID CARR-LOCKE: Well, we have scopes that can go lots of interesting places.

LULU: [laughs]

JENN: David said that in order to do the stomach and the colon, you'd have to knock Neil out. But ...

NEIL THEISE: "Well, why don't we look at the skin?" So we injected my vein with the dye.

DAVID CARR-LOCKE: Fluorescein.

JENN: And David just took the scope ...

DAVID CARR-LOCKE: Just holding it.

JENN: ... ran it across Neil's skin.

DAVID CARR-LOCKE: Scanned his skin, and sure enough ...

LULU: Is that it? Are we looking at it right now?

NEIL THEISE: That's it. That's it. Yeah, yeah, yeah.

LULU: Wow!

DAVID CARR-LOCKE: There it was. The white spaces are fluorescein.

JENN: Like, the bright orbs ...

LULU: We actually went up to David's OR at New York Presbyterian Hospital so we could do this on Jenn.

JENN: Oh! [laughs] That's awesome!

LATIF: Really? They scoped you?

JENN: [laughs] Yeah, it was, like—it was the coolest thing.

LATIF: And they saw the honeycomb fluid thing?

JENN: Exactly. They could see it in me, like, right away.

LATIF: Wow!

JENN: Anyway, David and Neil had now seen these honeycomb holes in the walls around the bile duct and around the skin cells, and because they knew that all these other places had the same cracks, it seemed like this honeycomb was probably surrounding all of our organs. Which raised a pretty simple question ...

NEIL THEISE: You know, it's just, what is it?

JENN: What is this structure they'd never noticed before? So ...

BECKY WELLS: Okay, so ...

JENN: ... they phone a friend.

NEIL THEISE: Becky Wells.

BECKY WELLS: Professor of medicine at the University of Pennsylvania.

JENN: So Becky does a lot of research into how organs, like, hold their structure and their shape.

BECKY WELLS: So the body's made up of cells, but there has to be something in between cells and around cells to keep it all together.

JENN: For example, if you think about an organ like the bile duct ...

BECKY WELLS: You know, you can't just have a little layer of cells floating around in the middle of the abdominal cavity. It would—you know, things would leak out, it would be very unstable, it would be very fragile. So the bile duct actually has layers of collagen to keep—you know, to keep the bile duct together.

JENN: And you'll find this throughout the body, not just around the bile duct but, like, in the spaces around and between most of our organs, there's this sort of thick, woven mat of collagen fibers.

BECKY WELLS: Exactly. You know, a very dense layer of collagen that served as a barrier.

JENN: But now here Neil had these pictures of these holes in the barrier, and he was so excited he actually threw his slides into a backpack and hopped a train down to Philly to Becky's lab.

BECKY WELLS: He came down—yes, exactly.

JENN: And Becky has some really cool instruments at her lab, including a microscope that could take a set of flat slides and turn them into a 3D image of that specimen.

BECKY WELLS: And we sat at this microscope in this completely dark room.

JENN: They turned it on.

BECKY WELLS: And what we could see was—it was almost like waves of hair.

JENN: Which was the collagen, but now in 3D they could see it was actually like a network of tubes.

BECKY WELLS: And we just start, you know, yelling and high-fiving each other.

NEIL THEISE: Yeah, yeah.

LATIF: And why?

JENN: Well, because as far as Neil could tell ...

NEIL THEISE: That meant that every collagen layer in the entire body, the dermis, the wrappings of all your muscles and your bones, the collagen that wraps around every artery and every vein, the collagen that gives structure to every visceral organ—your lungs, your heart, your liver, your kidneys, your pancreas, your GI tract, fibrous coverings inside your skull around the brain, the fibrous coverings around the nerves coming into the brain and going out of the brain ...

JENN: All of these places throughout the body that they'd always thought were just solid structural stuff were actually shot through with little tubes and tunnels. And inside of those tunnels there was this ...

NEIL THEISE: Fluid.

JENN: Eventually, they got ahold of some of the fluid.

NEIL THEISE: It's clear, but a little yellowy.

JENN: Sort of like ...

NEIL THEISE: Egg whites.

BECKY WELLS: So we have a colleague of Neil's analyze it to see what's actually in it.

JENN: And they discover this fluid has ...

NEIL THEISE: Water.

BECKY WELLS: Glucose.

NEIL THEISE: Insulin.

JENN: Hormones.

NEIL THEISE: Proteins.

BECKY WELLS: And ...

[ARCHIVE CLIP, advertisement: Hyaluronic acid.]

JENN: HA, or hyaluronic acid.

LATIF: Never heard of that.

JENN: Well, if you're a woman, you probably have, because ...

[ARCHIVE CLIP, advertisement: It's the skin care ingredient that everyone is searching for.]

JENN: ... you've been marketed on Instagram that you should buy it because it'll plump up your skin.

[ARCHIVE CLIP, advertisement: And reduces wrinkles for younger-looking skin.]

BECKY WELLS: So when people get injections, you know, to plump up their cheeks or whatever ...

JENN: Yeah.

BECKY WELLS: ... a lot of times it's hyaluronic acid, because that, you know, sort of functions like a pillow under the skin, for example. But we realized that hyaluronic acid would be a fantastic marker ...

JENN: To map out where the fluid is going, if it's going anywhere.

NEIL THEISE: So here's hyaluronic acid.

JENN: So they used a stain that could show them where the hyaluronic acid was, which could show them where the fluid was moving.

NEIL THEISE: There were all these little brown lines ...

JENN: That have this sort of flow.

NEIL THEISE: That's the hyaluronic acid. Like little tiny tributaries ...

JENN: From tissue to tissue, from organ to organ.

NEIL THEISE: ... reaching bigger streams that come together in big rivers. It's this vast fluid highway through the body that travels between organs, from one organ to the other.

JENN: Connecting everything to everything else ...

NEIL THEISE: Throughout the body.

JENN: And they eventually figured out 25 percent of the fluids going through our body is this stuff.

LATIF: What?

JENN: Yeah. Twenty five percent of the liquid in our body is flowing through this, and they had no idea what it was, or that it existed.

LATIF: Wait, and what percent is blood?

JENN: So we don't know the exact number, but it's less than that.

LATIF: Less than that?

JENN: Like, way less than that.

LULU: So it's four times the amount of blood.

LATIF: Four times the amount of blood?

LULU: Four times.

JENN: Yeah, four times.

LATIF: And also—sorry, as you mention it like that, like—because the circulatory system has a heart, which is, like, pumping stuff through—like ...

LULU: Yeah.

LATIF: ... what's the mechanism of stuff getting ...

LULU: Right, for—and, like, what's the directionality, and what's the contents of this ...

LATIF: Yeah, and why wouldn't it just all settle in your feet or something? That kind of thing.

LULU: Yeah.

NEIL THEISE: What I think we're about to show—we're working on this—is that the spaces around the heart have fluid in them. We know that. So when the heart contracts to push blood out the left ventricle, the spaces surrounding the heart get relaxed and fluid flows into them.

LULU: And then when the heart relaxes, the spaces around the heart get a little tighter and the fluid flows out.

LATIF: Huh!

LULU: That is the thinking. And they think the same thing might be going on with the lungs, because the lungs also expand and contract, expand and contract.

LATIF: Yeah.

LULU: So anyway, just a very quick recap.

LATIF: Yeah.

LULU: This tissue that everyone thought was dense like a wall and totally passive is almost, like, alive. It has fluids, it has ...

JENN: It's bumpin'.

LATIF: Crazy. The walls are juicy is what you're saying.

LULU: They were—yes.

JENN: It's a juicy wall that's pumping everywhere that they didn't even know.

LULU: And it seems to be a system, like a unified, body-wide system, similar to the nervous system or the circulatory system, that they had totally missed.

BECKY WELLS: I started thinking that my understanding of anatomy was extremely incomplete.

NEIL THEISE: And so ...

LULU: They were like, "We gotta publish. We gotta publish."

NEIL THEISE: Now the question is, what do we call it?

JENN: And they call it the interstitium.

LATIF: The interstitium. Huh.

JENN: What comes to mind when you hear that word?

LATIF: Well I mean, if I'm being honest, that's—if I was making up a fake organ, like, maybe that's the thing I would call it.

JENN: [laughs] Okay, fair enough. But for me, like, I don't know. I think it's actually really evocative.

LATIF: Hmm.

JENN: Maybe because I'm someone who, like, lives my life professionally between many different worlds and ways of thinking.

LATIF: Yeah.

JENN: Like, I like how it evokes spaces that are unseen and in between. But there's still this overarching question: what the [bleep] is it doing?

[computer alert]

JENN: [bleep]! There's that noise, sorry, in my background. It was my—I had a calendar update come up again, so ...

LULU: And we will try to figure out what the interstitium is doing after this short break.

JENN: [laughs]

LULU: Radiolab. Lulu here with Jenn.

JENN: Hello, hello.

LULU: And Latif.

LATIF: Hello.

LULU: Okay, when we left off we had just learned about this secret inside the human body, this piece of anatomy, a system—a human body part that nobody had noticed until, like, five years ago.

JENN: Well, not nobody. Like …

LULU: Okay, it might not be nobody. Okay. Well, tell—tell that story.

JENN: Okay.

LULU: Explain that.

JENN: So ...

NEIL THEISE: So my real job—this is the fun stuff—is liver pathology. And ...

[NEWS CLIP: A group of scientists believes it's discovered a fluid-filled tissue that makes up a previously unknown organ.]

NEIL THEISE: ... our interstitium work broke.

JENN: And shortly after, Neil was in China …

NEIL THEISE: ... doing collaborative stuff about liver disease ...

JENN: ... and some of the scientists and doctors there were like, "Hey, can you present on this interstitium stuff?"

NEIL THEISE: And I said sure.

JENN: So he gets to the stage, he gives his presentation, and after he's done ...

NEIL THEISE: A very high-level physician in China ...

JENN: Trained in Western medicine and traditional Chinese medicine ...

NEIL THEISE: He was given the first question, and his first question was, "What has been the response to this work of yours?" And I said, "Well, blah blah blah ..."

[NEWS CLIP: Scientists have expressed skepticism that the interstitium is its own organ.]

JENN: Like, the science world was arguing about what to call this thing.

NEIL THEISE: Is it an organ? Is it a tissue? Is it a system?

JENN: But whatever it is ...

[NEWS CLIP: Med school anatomy books may soon include a new chapter.]

JENN: ... people are talking about this new, exciting thing.

NEIL THEISE: And he said, "Well, we've been talking about it for 4,000 years."

LULU: [laughs]

JENN: Because traditional Chinese medicine has been working with fluid and channels and energy and systems throughout the whole body for thousands of years.

INTERPRETER: [speaking Chinese]

QIUSHENG CHEN: [speaking Chinese]

JENN: Now we couldn't find that doctor at the conference, but we did find another doctor in China who also had a strong reaction to the interstitium.

QIUSHENG CHEN: [speaking Chinese]

INTERPRETER: Okay, wow.

JENN: His name is Qiusheng Chen.

INTERPRETER: So our professor, Professor Chen, is not a smartass, and he didn't have ...

LULU: [laughs]

INTERPRETER: ... a reaction to be like, "Duh."

JENN: So we talked to Qiusheng through the help of a translator.

INTERPRETER: Wow!

LULU: [laughs]

INTERPRETER: [laughs] I didn't even understand what it is—happening in Chinese. Like, I'm mind-blown.

JENN: So Qiusheng is a professor at a veterinary school in China.

QIUSHENG CHEN: [speaking Chinese]

JENN: And he does a lot of research on ...

INTERPRETER: The kidneys of camels.

JENN: ... animal tissue.

INTERPRETER: The ...

QIUSHENG CHEN: Lungs.

INTERPRETER: ... lungs of yaks, yes.

LULU: Huh!

JENN: And apparently female turtles that can store sperm in their tissue ...

INTERPRETER: For up to one year long ...

LULU: [laughs] What?

INTERPRETER: ... and they can still be fertilized.

LULU: Whoa, that's wild!

QIUSHENG CHEN: Yeah, yeah.

JENN: But anyway ...

QIUSHENG CHEN: [speaking Chinese]

JENN: ... in 2018, he's on an airplane flying somewhere for work, and he comes across the interstitium paper.

QIUSHENG CHEN: [speaking Chinese]

JENN: And he suddenly had this kind of memory of being a little boy. He grew up in a rural village in China.

INTERPRETER: One day he had something that give him food poison. And it was so bad that he was having breathing problems.

QIUSHENG CHEN: [speaking Chinese]

JENN: So his parents took him to go see a doctor, who gave him acupuncture. And he had been given, like, a few needles on his hands, on his legs, and then he kind of, like, instantly felt this relief. Like, he sort of blushed. He was like, "It was kind of like ..."

INTERPRETER: I just, like, farted and then, like, you know, I'm good.

JENN: Like, a fart, in the sense of—like, this instantaneous—like, the discomfort just went away.

LATIF: Yeah.

JENN: It wasn't actually a fart, but it was a feeling of, you know, like, total relief.

QIUSHENG CHEN: [speaking Chinese]

JENN: So he's on a plane reading about the interstitium, and he was just, like, "God!" Like, it resurfaced that question he'd been carrying in his body since he was that little boy, which was like, "How did that work?"

INTERPRETER: [speaking Chinese]

QIUSHENG CHEN: [speaking Chinese]

JENN: So he starts reading about meridians, which are ...

INTERPRETER: Basically the network of acupuncture.

JENN: ... the pathways in the body through which life energy known as "chi" flows.

INTERPRETER: That's according to this book called ...

QIUSHENG CHEN: Huangdi Neijing.

INTERPRETER: …Huangdi Neijing, from 2005 years ago.

JENN: So he picks this pathway, this meridian that is known to help with the gut. And he can't actually do the experiment on people because it wouldn't be ethical, so he has to do it on animals.

LATIF: Wait, wait, wait, is animal acupuncture a thing?

JENN: Oh, big time.

LULU: I didn't—well, I didn't know that until ...

LATIF: Really!

LULU: ... reading this paper. I had no idea.

JENN: Yeah. My 14-year-old dog, we just took her to the doctor and they were like, "You could take her to acupuncture."

LULU: No way!

JENN: Yeah, yeah.

LULU: Really?

LATIF: Really?

JENN: She's got arthritis in her hind legs.

LATIF: And the idea is, like, it's like the same networks and pathways?

JENN: Yeah, pretty much.

LATIF: Huh. Who knew? Okay.

LULU: [laughs]

JENN: But so ...

QIUSHENG CHEN: [speaking Chinese]

JENN: ... Qiusheng got some rabbits.

INTERPRETER: Twenty-four rabbits.

JENN: Then gave the rabbits ...

INTERPRETER: Colitis.

JENN: ... colitis.

QIUSHENG CHEN: Yeah, yeah.

JENN: It's this disease that affects the lining of the colon. So these rabbits, they're bleeding. You know, they're having, like, little ulcers, they're losing weight rapidly. They're not doing well. But then he takes these little tiny needles and puts them into, like, the joint around the rabbit's, like, leg—like its knee. And the acupuncture works. Like, the inflammation gets better, the bleeding reduces, they start gaining weight again. Like, they're better.

INTERPRETER: And some of them are just all good, brand as new.

LULU: Totally cured. Just returned to normal.

INTERPRETER: Yes.

LULU: Wow!

QIUSHENG CHEN: [speaking Chinese]

JENN: So then he uses the interstitium paper almost like a map ...

QIUSHENG CHEN: [speaking Chinese]

JENN: ... to see if he can find anything in the interstitium that's happening that could explain this. And he finds ...

QIUSHENG CHEN: Telocytes.

INTERPRETER: Telocytes?

QIUSHENG CHEN: Telocytes.

INTERPRETER: Telocytes.

JENN: ... these cells ...

JENN: Oh, telocytes.

QIUSHENG CHEN: Yeah.

JENN: Telocytes, yes.

JENN: ... called telocytes, which are a newly-discovered cell ...

INTERPRETER: That is just one of the residents that lives in interstitium.

JENN: People aren't quite sure what it does. It seems to have some role in immune response regulation, some role in, like, cell-to-cell communication or signaling. But what he saw was that in the rabbits who got acupuncture, their telocytes were, like, super-activated. They were, like, throwing off chemical signals, talking to each other. They were just more active.

LATIF: So the telocytes are always there in the interstitium, but at least in these rabbits when they got acupuncture, they're on hyperdrive?

LULU: Voom, voom, voom, yeah.

JENN: Yeah.

LULU: So I was excited by it. Like, there are people in China who are really excited by it.

LULU: Does he feel like he has glimpsed the meridians that were proposed by Chinese medicine? Because this feels big. Like, this feels very big.

INTERPRETER: [speaking Chinese]

LULU: But his answer was basically ...

QIUSHENG CHEN: [speaking Chinese]

LULU: "All I can say is that we found what we found."

QIUSHENG CHEN: [speaking Chinese]

INTERPRETER: So I pushed again, asking if he thinks this is, you know, still a big thing. And he's like, "I cannot say that myself." So yeah.

LULU: Okay, point taken. So more to learn. He's excited by what he saw and he offers it to the world to learn more.

INTERPRETER: Mm-hmm.

LATIF: Yeah, because it's true. He hasn't found where they're going or coming from or if they—what they ...

JENN: Or exactly what they do.

LATIF: Yeah.

JENN: But ...

NEIL THEISE: When it comes to the body and modern approaches to health and healing ...

JENN: ... Neil says Western medicine has always had a difficult time talking about or understanding things like acupuncture.

NEIL THEISE: Because there was no Western-style anatomy to explain those clinical impressions, those personal experiences.

JENN: And Neil said even though we don't know how the interstitium might be a part of acupuncture, at the very least ...

NEIL THEISE: It provides a cultural bridge to allow people to have these discussions.

QIUSHENG CHEN: [speaking Chinese]

JENN: Which is kind of exactly what happened with Qiusheng, who said that, to him, when Neil and the team found the interstitium ...

QIUSHENG CHEN: [speaking Chinese]

INTERPRETER: They found the body, but they didn't find the soul.

JENN: ... they didn't find, like, the meaning, the reason why it's doing what it's doing, what animates it, what is its purpose. But they gave him a place to look and a place to bring these different ideas, these ancient, time-tested Eastern ideas together alongside modern Western medicine.

NEIL THEISE: And my hope is bit by bit, this community will be talking to people in the Chinese medicine community, and the Tibetan medicine community, and Ayurvedic medicine, because we're all talking about the same body.

LATIF: Okay. Okay, I get that. I get that, but can I just say—like, I don't know. Like, it feels like we're just learning. And I don't know, it's like—it feels like a jump to rope in this whole other ancient tradition of medicine. Like, maybe? Like, it looks like it has a resemblance, but it seems like it's way too early to go there. No?

LULU: Would you like something that's less of a maybe?

JENN: Yeah.

LATIF: Yeah!

JENN: Yeah. Okay, I'm excited about this. Go, Lulu.

LATIF: Okay, yeah.

LULU: Okay, so …

PETER FRIEDL: So how—how is everything? We should be ready to go.

LULU: Great!

LULU: At the very last minute, Jenn couldn't make this interview but I talked to this guy.

PETER FRIEDL: Yeah, my name is Peter Friedell. I am a medical doctor by training.

LULU: His name is Peter Friedell. For a long time he was a dermatologist.

PETER FRIEDL: But then discovered that maybe science is what I am best at.

LULU: Basically, he had seen so much skin cancer, melanoma, he'd seen so many people dying, and so he—he became a scientist. He kind of left practicing medicine behind and he became ...

LATIF: A cancer scientist?

LULU: Cancer scientist, yeah. And so he ...

PETER FRIEDL: At the end of the day, I switched from applying knowledge to generating knowledge.

LULU: And he was curious about, like, basically one of the most fundamental mysteries of cancer ...

PETER FRIEDL: Which is ...

LULU: How does it metastasize? Like, how does it show up in the skin?

PETER FRIEDL: And then at some point it shows up in lung or liver or the brain.

LULU: Like, how does it spread?

PETER FRIEDL: Yes, exactly.

LULU: All throughout the body.

PETER FRIEDL: Yes, so it was known ...

LULU: That obviously, once cancer gets into the blood ...

PETER FRIEDL: Or the lymphatic vessels ...

LULU: ... it spreads all over your body, and then you have to resort to chemo and things can get really, really bad. But what was not known was how exactly cancer goes from, like, your skin tissue to a blood vessel or a lymph vessel.

LATIF: That's hard? Like, it's harder than you would think?

LULU: Yeah, because even though that might be a tiny little journey ...

PETER FRIEDL: A couple of microns maybe, millimeters ...

LULU: ... from the point of view of a cancer cell, like, that journey is huge.

PETER FRIEDL: And a very tough one.

LULU: Because to a cancer cell, your body's tissue is like a thick, dense jungle. So basically, there was a hunch for a long time of how it worked.

PETER FRIEDL: It was thought that tumor cells ...

LULU: Come tearing through tissue with—he calls them ...

PETER FRIEDL: Bazookas.

LULU: ... bazookas or ...

PETER FRIEDL: Bush knives.

LULU: Like, machetes.

PETER FRIEDL: And scissors, all sorts of scissors.

LULU: To get through this tissue ...

PETER FRIEDL: ... in order to move ...

LULU: ... so that they can bushwhack their way to a vessel and then to the rest of your body.

PETER FRIEDL: So this was the premise.

LULU: And why was that the premise?

PETER FRIEDL: Well, we saw that cancer cells in the Petri dish, they cut everything into pieces.

LULU: He said, like, you can throw cancer cells and tissue cells into a Petri dish ...

PETER FRIEDL: And come back after the weekend ...

LULU: And the cancer will have ripped up that tissue.

PETER FRIEDL: And so all of big pharma were on it.

LULU: Peter says that's where millions of dollars of clinical trials of cancer research was focused in terms of, like—okay, that's how it moves through, so what do you need to do? You need to disarm the cancer cell.

PETER FRIEDL: But ...

LULU: Turned out even if you give medicine to people that takes away the bazookas, the bush knives ...

PETER FRIEDL: The tumor cells still invade perfectly.

LULU: Which was totally puzzling, because they knew these cancer cells have these weapons at their disposal, but it was like they didn't actually need them to spread. And discovering that was like ...

PETER FRIEDL: Hundreds of million dollars were burned.

LULU: ... devastating to the cancer research field. I mean, it was decades of drug development, of clinical trials, of hope poured into this type of treatment.

PETER FRIEDL: And people took a step back and wondered, "Okay, what did we get wrong?"

LULU: So early 2000s, Peter makes this jump into science. And he figures rather than studying what cancer does in a Petri dish, what he really wants to do is figure out a way to watch, in real time, how a cancer cell moves in the body. So what he does is he gets ...

PETER FRIEDL: Mice.

LULU: ... all these mice.

PETER FRIEDL: And then we ...

LULU: Take a mouse ...

PETER FRIEDL: Cut a little hole into it ...

LULU: … into the skin on its side ...

PETER FRIEDL: And build a frame out of plastic into this hole.

LULU: And then into that they put this little piece of glass.

PETER FRIEDL: The glass of an aquarium, so you can look through this glass into the living tissue.

LATIF: Wow!

LULU: Yeah! And then they take that mouse and give it ...

PETER FRIEDL: A skin tumor.

LULU: Melanoma, and a sleeping pill.

PETER FRIEDL: The mouse falls to sleep for three or four hours.

LULU: They put the mouse on its back underneath ...

PETER FRIEDL: Like a big, huge microscope.

LULU: A microscope so powerful it is the size of a room.

PETER FRIEDL: And then ...

LULU: They looked into the microscope, through the glass portal, into the mouse ...

PETER FRIEDL: And it was spectacularly colorful right from the beginning.

LULU: So ...

PETER FRIEDL: Imagine ...

LULU: All the skin tissue of the mouse ...

PETER FRIEDL: Was blue.

LULU: Like a blue jungle of skin tissue. And then the cancer cells, they were like these green little dots.

PETER FRIEDL: And the green dots were moving.

LULU: But what surprised Peter was that the cancer cells weren't moving like some wild horde, blowing up tissue wherever they could.

PETER FRIEDL: They were moving like a fluid, almost.

LULU: Instead, they were lining up ...

PETER FRIEDL: One after the other or neighbors even, together holding hands.

LULU: And streaming through ...

PETER FRIEDL: In extensive root-like fingers.

LULU: ... the mouse's skin. Basically, the cancer cells were finding little channels in the tissue where they could just zoom through it and get to a vessel.

PETER FRIEDL: In a way, it seemed to be like a highway-type system that the cells were exploiting.

LULU: And what were you thinking in that moment?

PETER FRIEDL: Oh, this is interesting. Let's—can we—can we observe it a little longer?

LULU: So you're just like—you're just like, fascinated?

PETER FRIEDL: Yeah, absolutely. It's like a child in a reef with all the fish and all the structures. It's like fascination—pure.

LULU: Because remember, he's seeing this a few years before Neil's and Becky and David's paper comes out.

LATIF: Yeah.

LULU: So he still, like, doesn't—this idea of a unified system, that isn't out in the world. But he is seeing the interstitium, like the channels of the interstitium.

LATIF: So what did—without that information, what did he think it—he thought that the cancer cells were making this channel?

LULU: No, no, no. He can tell that the channels are in there in the skin. So after the kind of transfixed awe wore off ...

PETER FRIEDL: We thought, holy shit, if every tissue has these channels ...

LULU: How are we ever gonna be able to stop the spread of cancer?

PETER FRIEDL: There are too many channels. This is—it's like it's—it's endless.

LULU: Like, there's just no way.

PETER FRIEDL: It's clear that we're not gonna stop them.

LULU: And so for years, Peter just sat staring at these cancer cells moving through these highways, feeling hopeless. Until one day, he was like, "What if we forget about the highways, trying to block them or stop them, and instead just go after the cancer cell?"

PETER FRIEDL: And kill it.

LULU: So what he does is he goes back to these mice and he just—poof!—blasts the cancer cells with radiation. And what he discovers is that the only cells that survive the blast ...

PETER FRIEDL: Are what we call the marathon runners.

LULU: ... are the cells that are running through the interstitium. So Peter starts pulling these cancer cells out of the mice.

PETER FRIEDL: To find what makes the marathon runner special, different from the rest.

LULU: And what he finds is that these marathon runners ...

PETER FRIEDL: They are smart, opportunistic creatures.

LULU: ... rather than deploying these bazookas to rip through tissue, they have these little claws that they use to get into the interstitium and move through it. And they can also use the claws to, like, fuel up in a way that makes them grow bigger and stronger and harder to kill.

PETER FRIEDL: That's already bad news, but it also is good news because if you now know what makes them special, you can take it away.

LULU: Fast forward, Peter develops these antibodies that basically declaw the cancer cells. And he gives these antibodies to the mice.

PETER FRIEDL: And you give radiation therapy at the same time. The marathon runners melt away and they die.

LULU: Hmm.

PETER FRIEDL: And we can cure the mice even in tumors that otherwise are not curable. So we could—and we also followed those mice up for half a year to check whether cells have made it out into the lungs or the liver or somewhere else, and nine out of ten mice were clean.

LULU: Whoa!

PETER FRIEDL: So that means we not only—we didn't need to block the roads, we bombarded the cars in a good way.

LULU: And he said the difference between that and chemo, where you just flood the body ...

LATIF: Right.

LULU: ... with everything ...

LATIF: Yeah.

LULU: ... is, like, a huge world of difference obviously, because, you know, you're not targeting the sick person's own immune system.

JENN: [sighs] I'm—I'm, like, finding myself getting—getting emotional about this.

LULU: Why?

JENN: Because my mom passed away from—from cancer, from lymphatic leukemia and lymphoma, which are system-wide. You know, that means they've gone through the whole—they're everywhere, you know? And she got chemo, and she had—she had too many white blood cells. And the chemo, they were too aggressive with it, and they knocked out so many white blood cells. You know, like you said, they just blast everything, that—then they couldn't—the white blood cell count couldn't get high enough to fight it anymore. Like, they over—overshot it.

LULU: Oh my God. Oh my God!

JENN: Yeah.

LULU: Is that—is that what—because I know she lived with it for a long time, right?

JENN: She did. It was a chronic lymphatic leukemia which, you know, is better than the acute, where people can pass very quickly. It's really aggressive. But it was really the chemo that ultimately killed her. And I think just hearing about Peter's work and—I don't know, it gives me, like, a little hope.

LULU: And I should say that Peter said this strategy of using antibodies and radiation ...

PETER FRIEDL: Whether then it is making it all the way into the clinics—as we know, one out of a thousand initially proposed strategies will make it to the patient. So we will—we will have to see.

LULU: It'll have to go through years of development, of trials in humans.

PETER FRIEDL: But at least proof of concept we made. We delivered.

LULU: And that's what feels big, because what Peter was finding in mice ...

NEIL THEISE: Tissues. So this is a slide of breast.

LULU: ... Neil and Becky are now seeing in humans.

NEIL THEISE: And here are cancer cells walking along through the interstitium like they've got a nice little path to follow through the woods.

LULU: Oh my God!

NEIL THEISE: Here they are just marching from the interstitium to get to the lymph nodes.

JENN: Yeah, so Neil and Becky, I kind of think of them as like, these cartographers, where they're essentially trying to make these maps ...

NEIL THEISE: Of every single organ.

JENN: ... of, like, where the interstitium is.

LULU: Where would it be in the womb?

NEIL THEISE: Uh ...

JENN: And where it isn't.

NEIL THEISE: There's very little, actually. It's interesting. This is one of the areas where you don't see a lot of interstitium.

JENN: And it's like they are publishing as fast as they can.

NEIL THEISE: We've got six papers that are heading their way towards publication.

JENN: And they're not claiming to know what the interstitium does or is doing throughout the body, they're just like, "Here are the maps. Now all these different fields, do with it what you will." So obviously, people who are interested in acupuncture have picked this up.

NEIL THEISE: But there's a lot of people who are focused on primarily Alzheimer's research.

JENN: They've been interested in the interstitium in the skull.

BECKY WELLS: Neil and I both participated in a conference at the National Institutes of Health in the spring on the interstitium as it relates to the kidney.

JENN: There's people looking at kidney function. There's people who hope the interstitium might help ...

BECKY WELLS: On understanding metabolic diseases like diabetes. Understanding bacteria in the body.

JENN: How infections might spread in places, even like your mouth.

BECKY WELLS: I gave a talk about this at the Pan Dental School. And, you know, there's a lot of bacteria in the mouth, right?

JENN: But ...

BECKY WELLS: We don't know. I mean, it's—it's sort of wide open right now.

LATIF: Huh. It's just sort of amazing to think, like, this little microscope goes into the body, and then opens up this whole new realm that we're just—you know, just beginning to learn about. Like, this is my favorite kind of technology story, where it unlocks a whole new part of our world, and literally a whole new part of ourselves that we just could not have seen otherwise.

JENN: Well, about that. It turns out you didn't actually need the microscope.

LATIF: Wait. It's not naked-eye visible, is it? No, it is? Really?

JENN: So ...

NEIL THEISE: So now what I'm gonna show you, we have cut—as I said, we cut open the small intestine and the wall of the stomach.

JENN: Now this is kind of like the wildest part of the story for me. So when we were in the lab with Neil, at one point he takes a cross-section of the small intestine in his hand.

NEIL THEISE: And you see this ...

JENN: And he started pulling at this thin ...

NEIL THEISE: That looks kind of thready?

JENN: ... like, layer of almost, like, translucent threads encasing the intestine.

LULU: That—that is the interstitium?

NEIL THEISE: That's the interstitium.

LATIF: What?

LULU: Yeah.

JENN: But, like, that was it. Like, that is it.

LULU: Is it okay to get that—this close?

NEIL THEISE: Yeah. See, like here? When I pull it, you see little threads sort of getting tense inside there.

LULU: Yeah.

JENN: Yeah.

NEIL THEISE: That's the interstitium.

LULU: Wow!

NEIL THEISE: Yeah. So you see ...

LULU: Wow! I thought this was like a technology story.

NEIL THEISE: No. No, no, no. No, so ...

LULU: Like, you got a fancy scope ...

NEIL THEISE: Any new technology that allows you to see things you didn't see before or see them in a different way is gonna reveal things you hadn't noticed. Some of them may not have been available to your eye. In this case, they were available to our eye, but we had never put it together.

JENN: And what Neil said was like, no one had put it together because we had been told to discount it.

BECKY WELLS: You know, we all read the same textbooks and look at the same drawings by the same people to explain what is seen in the human body.

JENN: And all these people had decided that this thready stuff that we were seeing in the body, like, it just didn't matter. It didn't do anything important.

NEIL THEISE: Yeah, we were looking—we saw it.

JENN: Yeah.

NEIL THEISE: But it had no meaning.

JENN: Or even like Neil, who had been seeing cracks in tissue in slides—he'd been told since med school ...

NEIL THEISE: This is nothing we even have to pay attention to.

JENN: ... that the cracks in the tissue, that they don't matter. Like, don't worry about the cracks.

NEIL THEISE: And I taught people these were just cracks for 30 years.

LULU: But so it's like when Jenn brought this story to us, I originally understood it as like, a fancy new technology reveals this body part we've missed forever. But it sounds like you're, like, no—like, is this actually a story just about beliefs getting in the way?

NEIL THEISE: Yeah. Beliefs and training and dogma. It comes back to the—Shunryu Suzuki Roshi, who was the founder of San Francisco's Zen Center, said that in the mind of the beginner, there are many possibilities, in the mind of the expert there are few. [laughs] I get choked up.

LULU: Why does that choke you up?

NEIL THEISE: Because it's so profound. What had I been taught that got in the way? What am I missing now?

LULU: This story was brought to us and reported by Jennifer Brandel. And before we go, we should say that Jenn has one more kind of brain-busting chapter about the interstitium. She just published an essay about it for Orion Magazine—Orion Magazine. It's called "Invisible Landscapes." Go read it. But Jenn, could you just give, like, a Cliff's Notes?

JENN: Sure. Yeah. So I mean, truth be told, I'm most interested in the interstitium's metaphorical value. Like, if we've missed seeing this thing that connects so many organs in our bodies, might we be missing analogous things in society? Does that make sense? [laughs]

LULU: Not quite. Say one more beat, one more beat. What does that mean?

JENN: Okay.

LULU: An interstitium in society, what does that mean?

JENN: Yeah, like, so just briefly, like I mentioned at the top, I'm a person who operates between different organs in society, like—or as we call them, organizations, you know, between journalism, tech, government, democracy. And in learning about the interstitium, it was kind of like the skeleton key for me that made me realize that, like, there's this whole invisible thing that has been discounted: the people, the roles that do this connective work.

LULU: Like a kind of work, almost?

JENN: Yeah, it's like a kind of work. It's been ignored. It's like it doesn't have a job description. It's discounted. And, like, I think it's key to the health of the whole body, like the whole economy. And so in the essay I give some examples of what I mean.

LULU: Yeah, and I guess I just kind of want to hype you now. Like, you talk about work you did connecting the city of Chicago during COVID to hospitals, churches, hotels, to help people in need. It's very concrete stuff. It's really neat.

JENN: Yeah.

LULU: Yeah, it's really neat.

JENN: Oh, well thanks, Lulu. I mean, basically it's just making the interstitium-like people visible in society, and talking about how the more we value it, the more we notice, invest in it, it could have hopefully positive ramifications for the health of the economy and, I don't know, stuff like that.

LULU: Stuff like that. Go check it. Again, it is called, "Invisible Landscapes," and you can read it at OrionMagazine.org. And if you are interested in geeking out in more scientific ideas, Neil Theise—Dr. Neil Theise just published a book that is called Notes on Complexity: A Scientific Theory of Connection, Consciousness and Being. It is really profound and great. Go check that one out as well, Notes on Complexity by Dr. Neil Theise.

LULU: This episode was produced by Matthew Kielty, with production help from Ekedi Fausther-Keeys, mixing help from Arianne Wack, fact-checking by Natalie Middleton. It was edited by Alex Neason.

LULU: Big special thanks to Jessica Clark, Aaron Wickenden, Mahda Zepeda, Darryl Holliday, Dr. Amy Chang, Kate Sassoon, Guy Huntley, John Jacobson, the Village Zendo, Scotty G, and rest in peace to Mavis, the 14-year-old dog.

LULU: Oh, and before we go, I guess we should just sign off with what happened after Jenn was injected with fluorescent dye to get scoped. The doctors told her that if she went to a dance club she would glow under the black light. But instead, she just went home, drank some tea. And ...

JENN: Okay, I'm just getting back to the Airbnb I'm staying at in Brooklyn, and I have been told that the dye that was injected is gonna make my pee green. We're gonna see. I have not urinated since—well, for a while. Since the dye was injected. So all right, let's see. Here goes. Okay, let's take a look. Whoa! [laughs] Oh, wow! It's, like, highlighter yellow-green. It's really—yeah, it's like neon greeny yellow. Wild. Okay, I'm gonna take a photo. This is what we get to do for work. What a privilege. [laughs]

[LISTENER: Radiolab was created by Jad Abumrad and is edited by Soren Wheeler. Lulu Miller and Latif Nasser are our co-hosts. Dylan Keefe is our director of sound design. Our staff includes: Simon Adler, Jeremy Bloom, Becca Bressler, Ekedi Fausther-Keeys, W. Harry Fortuna, David Gebel, Maria Paz Gutiérrez, Sindhu Gnanasambandan, Matt Kielty, Annie McEwen, Alex Neason, Alyssa Jeong Perry, Sarah Qari, Sarah Sandbach, Arianne Wack, Pat Walters and Molly Webster, with help from Timmy Broderick. Our fact-checkers are Diane Kelly, Emily Krieger and Natalie Middleton.]

[LISTENER: Hi, my name's Michael Smith. I'm calling from Pennington, New Jersey. Leadership support for Radiolab's science programming is provided by the Gordon and Betty Moore Foundation, Science Sandbox, a Simons Foundation initiative, and the John Templeton Foundation. Foundational support for Radiolab was provided by the Alfred P. Sloan Foundation.]

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