The Interstitium
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It can seem like a privilege to have hope these days. Playwright Lynn Nottage and songwriter David Byrne say maybe we're not tapping the right sources. On the next Notes from America, finding optimism in unexpected places. Listen wherever you get your podcasts.

This is Radiolab. I'm Lulu Miller. I'm Latif Nasser. Oh, hello. Along with reporter Jen Brandel. Hi. Latif, Jen, have you guys met? I don't think so. No. So Jen is a radio reporter who I've known for a long time.

But these days... I'm a little hard to explain. I have been a journalist. I'm a CEO of a tech company right now. I work between a few worlds, between entrepreneurship, democracy, media, blah, blah, blah. Yeah. Well. It's 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. Right. And that'll maybe come back.

Okay, so I don't know. Shall we just, shall we begin? Are you ready for a journey? Yeah. Okay, so we're going to just to kick it off. Caffeinated, bageled, ready to go. We are going to start now.

Inside a hospital. We're fourth. On the fourth floor. Fourth floor. Going up. Jen and I are walking around. It's NYU Hospital. We're trailing some doctors. And we're in this part of the hospital I had never thought about that exists, but it very much exists. So this is Lulu. This is Jen. Hi. We have permission to be here. So we walk into this room that looks a little bit like an industrial kitchen. We just can't mention any identifiers. 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 human organs. So that's small intestine coming here. Organs I've heard about but never seen before. And this is the pancreas. They pulled out a whole stomach. Just like a big orangey red chunk of meat. And they pulled out. Here's the dome of the uterus. Wow. A uterus? This is your ovary. Whoa. Whoa.

And they pulled out. Here's a large fatty red tissue, and that's the breast tissue. A whole breast they pulled out. Wow, okay. A liver. Is this a brain? No, this is skin. Just organ after organ. Are these organs for training or? No, no, no, no. These are fresh. It looks like we're seeing blood. Some of them were dripping blood. Yeah, there's blood. The red stuff is blood. Some were dripping bile. These were organs that had come out of people that day.

And so what that room is, is it's a pathology lab where they are looking at anything that has been taken out of or off of a patient in the hospital. Because maybe that person's getting a transplant or maybe they had...

That's cancer. A tumor removed. Wow, that's a big, that's like a tennis ball amount. It's like dizzying because it's these pieces of people, but they hold these full, you know someone like two floors above you is going through a huge day. Right. But.

The reason why we were there that day was to see a body part. Should we just go now? Yeah. Oh, okay. A sort of... We're giving consent for this procedure, right? I am giving consent. Organ. Just tested the syringe. A couple drops came out. Here comes the big needle. Inside the human body that scientists had. Whoa, there it is.

Completely missed. Is that it? Are we looking at it right now? That's it. Even though it had just been sitting there. Oh my gosh. Wow. All this time inside of all of us. An organ? Yeah. A body part. A big deal body part. A big deal body part. A big deal body part that we'd missed. Until like five years ago. What? What?

Yeah. And so today we are going to bring you... How could that be? Well, that's the story we're going to tell you. How we missed it. People have been looking at the human body for like since the beginning. Yep. Exactly. Which is why it's so bizarre that we missed it.

I don't even know if I believe you. I'm like in disbelief here. As were many. Yeah, so we're going to tell you the story of what this mysterious body part is, what its name is, what it might be doing, why we miss it, how knowing about it might change our lives, our health, and maybe even like society a little bit. Really? But I'm going to pipe down because Jen's going to tell you the rest. All right. Oh, great. Now I just had a Google meeting pop up. Let me just kill all these things. Stop it. Okay. From your 17 other jobs that you work. Yeah, exactly. Yeah.

Okay. All right. Okay.

So the story starts with this guy, Neil Theis. Hello. Hey, Neil. How are you doing? Dr. Neil Theis. I'm good. Okay, let me. So Neil was actually one of the doctors. So this is Lulu. This is Jen. Hi, hi. Who is showing us around the lab. Okay. 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 going to be a rabbi for part of his life. So I was sort of all over the map. The class is over.

Classic rabbi programmer. No, exactly. Exactly. What about why did you want to become a doctor in the first place? Sorry, I know this could be a long story, but quickly, like in summation. 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 going to get old, I'll never get married, I'm never going to have kids, and I'll be doing Hitler's job for him because of that. And I'm going to grow old and die alone.

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... My mother called me up and said, oh, bad news. The doctor that she had worked for and who had delivered him and his brother in his hometown in Connecticut... Had died of a heart attack on the golf course that morning.

And the funeral was going to 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. So that's why I went to medical school. 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? 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 my life won't be meaningless. So he goes off to med school. Discovered pathology in the middle of it and was like, oh...

I like this. Which is funny because in pathology... Opening up the small intestine. You're mostly dealing with... I'm lifting up the lining of the stomach. The parts of patients, not the actual people themselves. But I just really love looking at beautiful puzzles. Because a lot of what pathology is... So I've got this big stack of slides here. ...is taking an organ and making a tiny... Cut off a very, very thin slice. ...little sample of it, putting it on a slide, adding some stains to it to give it

color. And then we'll look at it under the microscope. Where he'll see... A pattern of colors. Whoa! Shapes. Oh my god. Relationships between the shapes. Okay. Wow. So each cell has a particular shape. 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...

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. When I was at Beth Israel Medical Center in New York. So he had this cush job at Beth Israel. It was very luxurious. I had my own room with a multi-headed microscope. Removed from all the action so he could focus on his microscope all day long. And a colleague walks in one day. David Carlock. Neil told us you are a scope jockey. He would say that.

Do you know what that means? Is that a term of art? No, no. It's very, very derogatory. Is it like a dig of someone who likes looking at microscopes? No, no, no, no. An endoscope. Oh, endoscope. Oh, okay. Yeah. They like to put it up the places and look around. Yeah, or down the places and look around. Down and up, through all the ends. Yes. Very good. That's what I do. He's a gastroenterologist. Thank you. And so he comes into Neil's office and he's like, hey, man, this is why I'm dressed like

No, it's probably more like, excuse me, Dr. Thies. We've got this new scope. Until now, gastroenterologists were often in the dark. A very fancy endoscope. Basically a miniature microscope. Enabling you to see what you've been missing so far. So you can see cells in a living person. With real-time microscopic information critical to their decision-making process. And it was showing us something that we didn't understand.

In particular, it was showing them something in... Bile duct has arrived. The bile duct. The bile duct. So the bile duct is this tiny, tiny organ. It looks like just a tube. We looked at it with Neil. I don't know, three inches long, two and a half, three inches long. It's like a piece of spaghetti. Oh, wow. Like a little piece of spaghetti. It's called...

More ziti. A dried ziti, little mini ziti. Where is the bile duct? Sort of if you go about three or four inches above your belly button, straight in. And what does the bile duct do again? 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.

Okay. So a super important organ. It's purely a passive tube, but it does a lot of important things. 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. One of the causes of problems like that is a narrowing in the bile duct, which could be benign or it could be cancerous.

So the patient gets sent to David's OR. And then we give the patient an injection of something called... This is fluorescein. Fluorescein. This is actually what the microscope sees, this fluorescent liquid. It will distribute itself through the blood system and fluid spaces within seconds. It basically lights up wherever there is fluid in your body. And then after the shot...

David grabs his fancy scope. So it kind of just looks like a big black hose. It's about as thick as your finger. With a flashlight at the end. And then, he threads the scope. Down the esophagus, past the stomach. Into the small intestine. And into the bile duct. So David and his colleague Petros Benias, 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. If you could imagine a sort of honeycomb appearance. Where they'd always seen just like a dark wall. There were now these glowing holes where the fluorescein was showing with these little dark fibers around them. And this nice regular honeycomb shape. And this is in patients who have bile ducts that are diseased or? No, no, no. In a normal bile duct. In a normal healthy bile duct he was seeing again and again this honeycomb of lit up holes in the wall. Well, why haven't we seen this before?

And so David took some pictures of the honeycomb. We went to Neil and they showed me the pictures and said, look, what is this thing? What does this correspond to that you've been looking at for the last 30 years? And I was like, I don't know what the hell I'm looking at. I just don't know what I'm looking at. 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. There's no spaces there. It's pretty much solid. Like a dense wall.

So he's looking at all these lit up holes thinking... This doesn't make any sense. Really intense cognitive dissonance, which is a lovely place to be scientifically. For some people. 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? So Neil took these images of the honeycomb. I couldn't find them in any textbook. And he would show them to colleagues on his lunch break. And people were making fun of me. They were like, Neil, he's just wild about bile. People just didn't really care. Yeah, yeah. So I don't know how long it took. But eventually Neil was like, wait a second. When David uses his new scope. What you've been missing so far.

He's looking at live tissue, but... All the tissue I see is dead.

So a specimen comes down from the operating room. So whenever an organ lands on the lab desk of a pathologist. You drop it in formaldehyde. You do all this stuff to it. And you wash it. Dip it in alcohol. Put it into wax. Because you're mummifying it. You're dehydrating it. You're turning it into a mummy of itself. Then you shave off a super thin slice of it. And put it under the microscope. Bill showed us his lie to the bile duct.

Now, see all these cracks? Yeah. You see all these faint little cracks in the wall? We always thought they were cracks. 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. But they're not.

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... They're the remnants of the living spaces. They were what was left behind when the holes of this honeycomb dried out and...

would sort of collapse on itself. It's sort of like, have you seen those tiny little sponges that are dehydrated? And then you put them in water and they go like, like the ones that are shaped like a dinosaur or something. The ones that are like a pellet. And then it's like, whoa, it's a dinosaur. Right. Yeah. So you can think about the way that slides have been being made for like 100 years, like the pellet. That's what they've been looking at. Oh. But with David's scope, they were seeing the pellet expanded into the sponge form full

Full of holes, which is how the walls around a real living bile duct actually look. And so we realized bile ducts are not like anything we thought they were. Huh. Which, you know. Who cares about the bile duct, right? Who actually cares that the bile duct is encased in a spongy honeycomb wall? Big deal. But this is where it gets interesting. So within days...

Neil is back to doing clinical work. And he started to look at tissues that he sees every day, but now with a new eye. So one day he gets sent a breast. 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. So Neil did his thing. Formaldehyde, alcohol, wax. Took some of the healthy skin, put it under the microscope and saw. It had the same cracks. So that was exciting. And it wasn't just the skin. He was seeing those cracks in the collagen around the stomach, around the

There are cracks. Tiny little cracks in a dense wall. 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. And Neil, of course, being Neil. Said, how about we use the fancy endoscope? On him. To see if the places where you're usually seeing cracks might also, not dried out, have this network of fluid-filled holes. ♪

Do it on me. Well, we have scopes that can go lots of interesting places. David said that in order to do the stomach and the colon, you'd have to knock Neil out, but... Well, why don't we look at the skin?

So we injected my vein with the dye, fluorescein. And David just took the scope. Just holding it. Ran it across Neil's skin. Scanned his skin. And sure enough. So is that it? Are we looking at it right now? That's it. Yeah. Wow. There it was. The white spaces are fluorescein. Like the bright orbs. We actually went up to David's OR at New York Presbyterian Hospital so we could do this on Jen. Oh, that's awesome. So we went.

Really? They scoped you? Yeah. It was like, it was the coolest thing. And they saw the honeycomb fluid thing? Exactly. They could see it in me, like right away. Wow. 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. You know, it's just...

What is it? What is this structure they'd never noticed before? So. Okay, so. They phone a friend. Becky Wells. Professor of medicine at the University of Pennsylvania. So Becky does a lot of research into how organs like hold their structure and their shape. 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. For example, if you think about an organ like the bile duct... 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. 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. Exactly. You know, a very dense layer of collagen that served as a barrier.

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 on a train down to Philly to Becky's lab. He came down, yes, exactly. And Becky has some really cool instruments in her lab.

including a microscope that could take a set of flat slides and turn them into a 3D image of that specimen. And we sat at this microscope in this completely dark room. They turned it on. And what we could see was, it was almost like waves of hair. Which was the collagen. But now, in 3D, they could see it was actually like a network of tubes. And we just start, you know, yelling and high-fiving each other. Yeah, yeah.

And, uh, why? Well, because as far as Neil could tell... 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. All of these places throughout the body that they'd always thought were just solid structural stuff

were actually shot through with little tubes in tunnels. And inside of those tunnels, there was this... Fluid.

Eventually, they got a hold of some of the fluid. It's clear, but a little yellowy. Sort of like egg whites. So we have a colleague of Neil's analyze it to see what's actually in it. And they discover this fluid has water, glucose, insulin, hormones, proteins, and hyaluronic acid. H-A or hyaluronic acid. Never heard of that. Well, if you're a woman, you probably have because it's the skincare ingredient that everyone is searching for.

You've been marketed on Instagram that you should buy it because it'll plump up your skin. And reduces wrinkles for younger looking skin. So when people get injections, you know, to plump up their cheeks or whatever. Yeah. 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. To map out where the fluid is going, if it's going anywhere. So here's hyaluronic acid. So they used a stain that could show them where the hyaluronic acid was, which could show them where the fluid was moving. There were all these little...

brown lines that have this sort of flow. That's the hyaluronic acid. Like little tiny tributaries from tissue to tissue, from organ to organ 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 connecting everything to everything else throughout the body.

And they eventually figured out 25% of the fluid going through our body is this stuff. What? Yeah. 25% of the liquid in our body is flowing through this. And they had no idea what it was or that it existed. Wait, and what percent is blood? So we don't know the exact number, but...

It's less than that. Less than that? It's like four. So it's four times the amount of blood. Four times the amount of blood. Yeah, four times. And also, sorry, as you mention it like that,

Like because the circulatory system has a heart, which is like pumping stuff through. Like what's the mechanism of stuff getting – Yeah, and like what's the directionality and what's the contents of this? Yeah, and like why wouldn't it just all settle in your feet or something, that kind of thing. Yeah. 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. And then when the heart relaxes, the spaces around the heart get a little tighter and the fluid flows out. That is the thinking. And I think the same thing might be going on with the lungs because the lungs also expand and contract, expand and contract. Yeah.

Anyway, just a very quick recap. Yeah. This tissue that everyone thought was dense like a wall and totally passive is almost like alive. It has fluids. It has a... It's bumping. Crazy. The walls are juicy is what you're saying. It's a juicy wall that's pumping everywhere that they didn't even know. 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. Yeah.

I started thinking that my understanding of anatomy was extremely incomplete. And so— They're like, we got to publish. We got to publish. Now the question is, what do we call it? And they call it the interstitium. The interstitium.

What comes to mind when you hear that word? 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. Okay, fair enough. But for me, like, I don't know. I think it's actually really evocative. Maybe because I'm someone who like lives my life professionally between many different worlds and ways of thinking. Like, I like how it evokes spaces that are unseen and in between. Yeah.

But there's still this overarching question. What the f*** is it doing? There's that noise. Sorry, in my background, it was mine. I had a calendar update come up again. And we will try to figure out what the interstitium is doing after this short break. Hi, Rebecca Murray here from Mount Vernon, Washington. I'm a member of Radiolab's exclusive membership program, The

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This week on the New Yorker Radio Hour, Bradley Cooper. In his new film about the conductor, Leonard Bernstein, Cooper had to conduct one of the world's top orchestras for real. Scariest thing I've ever done by far. I mean, not even close. Singing at the Oscars live, performing at Glastonbury, nothing even comes close.

Bradley Cooper on Maestro. That's the New Yorker Radio Hour from WNYC Studios. Listen wherever you get your podcasts. Radio Lab. Lulu here with Jen. Hello, hello. And Latif. Hello. 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. Well, not nobody. Okay, it might not be nobody. Okay, well, tell that story. Explain that. So my real job, this is the fun stuff, is liver pathology. A group of scientists believes it's discovered a fluid-filled tissue that makes up a previously unknown organ. Our interstitium work broke. And shortly after Neil was in China. Doing collaborative stuff about

liver disease. And some of the scientists and doctors there were like, "Hey, can you present on this interstitium stuff?" And I said, "Sure." So he gets to the stage, he gives his presentation, and after he's done — A very high-level physician in China. — trained in Western medicine and traditional Chinese medicine. 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. Scientists have expressed skepticism that the interstitium is its own organ. Like the science world was arguing about what to call this thing. Is it an organ? Is it a tissue? Is it a system? But whatever it is. Med school anatomy books may soon include a new chapter. People are talking about this new exciting thing. And he said, well, we've been talking about it for 4,000 years.

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

His name is Quxing Chen. So our professor, Professor Chen, is not a smart ass. And he didn't have...

The reaction be like, duh. So we talked to Qisheng through the help of a translator. Wow. I don't even understand what is happening in Chinese. Like, I'm mind blown. So Qisheng is a professor at a veterinary school in China. And he does a lot of research on... The kidneys of camels. Animal tissue. The...

Yaks. Lungs of yaks, yes. Huh. And apparently female turtles that can store sperm in their tissue? For up to one year long. What? And they can still be fertilized. Whoa, that's wild. Yeah, yeah. But anyway, in 2018, he's on an airplane flying somewhere for work and he comes across the interstitium paper. And he suddenly had this...

kind of memory of being a little boy. He grew up in a rural village in China. One day, he had something that gave him food poison, and it was so bad that he was having breathing problems. 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 that

This relief. Like, he sort of blushed. He was like, it was kind of like... I just, like, farted and then, like, you know, I'm good. Like a fart in that, the sense of, like, this instantaneous, like, the discomfort just went away. Yeah. It wasn't actually a fart, but it was a feeling of, you know, like, total relief. The circulation system and the nerve system

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? I found it very obvious that the TC of the 發病组

So he starts reading about meridians, which are... Basically, the network of acupuncture. The pathways in the body through which life energy, known as qi, flows. That's, according to this book...

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. Wait, wait, wait. Is animal acupuncture a thing? I didn't know.

didn't know that until reading this paper. I had no idea. My 14-year-old dog, we just took her to the doctor and they're like, you could take her to acupuncture. No way. Really? She's got arthritis in her hind legs. And the idea is like, it's like the same networks and pathways. Yeah, pretty much. Huh. Who knew? Okay.

But so, Qusheng got some rabbits. 24 rabbits? Then gave the rabbits. Colitis. Colitis. Yes, yes. 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 getting weight again. Like they're they're better. And some of them are just all good.

Totally cured, just returned to normal. Yeah. Wow. So then, he uses the interstitium paper, almost like a map, to see if he can find anything in the interstitium that's happening that could explain this. And he finds...

These cells. Oh, telocytes. Yes. Telocytes, yes. Called telocytes, which are a newly discovered cell. That is just one of the residents that lives in interstitium. 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. So the telocytes are always there in the interstitium, but...

at least in these rabbits, when they got acupuncture, they're on hyperdrive? Foom, foom, foom. Yeah, yeah. So I was excited by it. Like there are people in China who are really excited by it. Does he feel like he has glimpsed the meridians that were proposed by Chinese medicine? Because this feels big.

Like, this feels very big. But his answer was basically, all I can say is that we found what we found. So I pushed again. So you didn't think you were asking if he thinks this is, you know, still a big thing? No, I can't say it myself.

And he's like, I cannot say that myself. So, yeah. Okay. Point taken. So more to learn. He's excited by what he saw and he offers it to the world to learn more. Yeah, because it's true. He hasn't found where they're going or coming from or if they... Or exactly what they do. Yeah. But... When it comes to the body and modern...

approaches to health and healing. Neil says Western medicine has always had a difficult time talking about or understanding things like acupuncture. Because there was no Western-style anatomy to explain those clinical impressions, those

those personal experiences. And Neil said, even though we don't know how the interstitium might be a part of acupuncture, at the very least, it provides a cultural bridge to allow people to have these discussions. Which is kind of exactly what happened with Q. Shang, who said that to him, when Neil and the team found the interstitium, they found the body, but they didn't find the soul.

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. 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. OK, OK, 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? Would you like something that's less of a maybe? Yeah. Okay.

Yeah. Okay. I'm excited about this. Go, Lulu. Yeah. Okay. So how is everything? We should be ready to go. Great. At the very last minute, Jen couldn't make this interview, but I talked to this guy. Yeah. My name is Peter Friedl. I'm a medical doctor at

His name is Peter Friedl. For a long time, he was a dermatologist. But then discovered that maybe science is what I am best at. Basically, he had seen so much skin cancer, melanoma. He'd seen so many people dying. And so he became a scientist. He kind of left practicing medicine behind and he became... A cancer scientist. Cancer scientist, yeah. And so he... At the end of the day, I switched from applying knowledge to generating knowledge.

And he was curious about like basically one of the most fundamental mysteries of cancer. Which is? How does it metastasize? Like how does it show up in the skin? And then at some point shows up in lung or liver or the brain. Like how does it spread? Yes, exactly. All throughout the body. Yeah, so it was known. That obviously once cancer gets into the blood. Or the lymphatic vessels. It spreads all over the 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

to a blood vessel or a lymph vessel. That's hard. It's like harder than you would think. Yeah, because even though that might be a tiny little journey... A couple of microns, maybe millimeters. From the point of view of a cancer cell, like that journey is huge. And a very tough one. 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. It was thought that tumor cells...

come tearing through tissue with, he calls them bazookas, or like machetes, to get through this tissue so that they can bushwhack their way to a vessel that

and then to the rest of your body. So this was the premise. And why was that the premise? Well, we saw that cancer cells in the Petri dish, they cut everything into pieces. He says, like, you can throw cancer cells and tissue cells into a Petri dish. And come back after the weekend. And the cancer will have ripped up

And so all big pharma were on it. Peter says that's where millions of dollars of clinical trials of cancer research was focused in terms of like, OK, that's how it moves through. So what do you need to do? You need to disarm the cancer cell. But turned out, even if you give medicine to people that takes away the bazookas, the bush knives, the tumor cells still invade perfectly.

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... Hundreds of million dollars were burned. 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. And people took a step back and wondered, OK, what did we get wrong?

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.

Wow.

Yeah. And then they take that mouse and give it a skin tumor, melanoma, and a sleeping pill. The mouse falls to sleep for three or four hours. They put the mouse on its back underneath like a big, huge microscope. A microscope so powerful it is the size of a room. And then...

They looked into the microscope, through the glass portal, into the mouse. And it was spectacularly colorful right from the beginning. So, imagine all the skin tissue of the mouse was blue, like a blue jungle of skin tissue. And then the cancer cells, they were like these green little dots. And the green dots were moving. But what surprised Peter was that the cancer cells

But the cancer cells weren't moving like some wild horde blowing up tissue wherever they could. They were moving like a fluid, almost. Instead, they were lining up. One after the other or neighbors even together holding hands. And streaming through. Extensive root-like fingers. 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.

In a way, it seemed to be like a highway type system that the sales were exploiting. And what were you thinking in that moment? Oh, this is interesting. Let's, can we...

Can we observe it a little longer? So you're just like, you're just like fascinated. Yeah, absolutely. It's like a child in a reef with all the fish and all the structures. It's like fascination pure. Because remember, he's seeing this a few years before Niels and Becky and David's paper comes out. 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. So what did, without that information, what did he think? He thought that the cancer cells were making this channel? No, no, no. He can tell that the channels are in there, in the skin. So after the kind of transfixed awe wore off. We thought, holy shit.

If every tissue has these channels... How are we ever going to be able to stop the spread of cancer? There are too many channels. It's like it's endless. Like there's just no way. It's clear we're not going to stop them. 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? And kill it. So what he does is he goes back to these mice and he just...

blasts the cancer cells with radiation. And what he discovers is that the only cells that survive the blast are what we call the marathon runners, are the cells that are running through the interstitium. So Peter starts pulling these cancer cells out of the mice to find what makes the marathon runner special, different from the rest. And what he finds is that these marathon runners, they are smart, opportunistic creatures. 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. 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.

Fast forward, Peter develops these antibodies that basically declaw the cancer cells. And he gives these antibodies to the mice. And you give radiation therapy at the same time. The marathon runners melt away and they die. 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 had made it out into the lungs or the liver or somewhere else and

Nine out of 10 mice were clean. Whoa. So that means we not only, we didn't need to block the roads, we bombarded the cars in a good way. And he said the difference between that and chemo, where you just flood the body with everything, is like a huge world of difference, obviously, because, you know, you're not targeting the sick person's own immune system. I'm...

I'm like finding myself getting, um, getting emotional about this. Um, why? Um, because my, my mom passed away from, uh, from cancer, from lymphatic leukemia and lymphoma, which are system wide. Um,

you know, that means they've gone through the whole, they're everywhere, you know, and, 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 overshot it. Oh my God. Is that what, because I know she lived with it for a long time, right? She did. It was a chronic lymphatic leukemia, which 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 that,

about Peter's work and I don't know, it gives me like a little hope. And I should say that Peter said this strategy of using antibodies and radiation. Whether then it is making it, it's 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 have to see. We'll have to go through years of development of trials in humans. But at least proof of concept we made.

And that's what feels big because what Peter was finding in mice... So this is a slide of breast. Neil and Becky are now seeing in humans. And here are cancer cells walking along through the interstitium like they've got a nice little path to follow through the woods. Here they are just marching from the interstitium to get to the lymph nodes. Yeah, so Neil and Becky, I kind of think of them as like these cartographers.

where they're essentially trying to make these maps of every single organ of like where the interstitium is where would it be in the womb

And where it isn't. There's very little, actually. It's interesting. This is one of the areas where you don't see a lot of interstitium. And it's like they are publishing as fast as they can. We've got six papers that are heading their way towards publication. 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. But there's a lot of people who are focused on primarily Alzheimer's research. They've been interested in the interstitium in the skull. 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. There's people looking at kidney function. There's people who hope the interstitium might help on understanding metabolic diseases like diabetes, understanding bacteria in the body, how infections might spread in places even like your

mouth? I gave a talk about this at the pendental school and, you know, there's a lot of bacteria in the mouth, right? But we don't know. I mean, it's sort of wide open right now. 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. Well, about that. Turns out you didn't actually need the microscope. Wait, it's not naked eye visible, is it? No. It is? Really? So?

So now what I'm going to show you, we have cut, as I said, we cut open the small intestine and the wall of the stomach. 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. And you see this. And he started pulling at this thin. It looks kind of thready. Like layer of almost like translucent threads encasing the intestine. That.

That is the interstitium? That's the interstitium. What? Yeah. But, like, that was it. Like, that is it. Is it okay to get that this close? See, like here? Yeah.

When I pull it, you see little threads sort of getting tense inside there. Yeah. Yeah. That's the interstitial. Wow. Yeah. Wow. I thought this was like a technology. No, no, no, no. It's like you got a fancy scope. Any new technology that allows you to see things you didn't see before or see them in a different way is going to 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. - And what Neil said was like, no one had put it together because we've been told to discount it. 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. 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. - Yeah, we were looking, we saw it,

But it had no meaning. Or even like Neil, who had been seeing cracks in tissue in slides he'd been told since med school. This is nothing we even have to pay attention to. That the cracks in the tissue, that they don't matter. Like, don't worry about the cracks. And I taught people these were just cracks for 30 years. But so it's like when Jen 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? Beliefs and training and dogma. It comes back to the Shinryu Suzuki Roshi, who was the founder of San Francisco Zen Center, said that in the mind of the beginner, there are many possibilities. In the mind of the expert, there are few. I get choked up. Why does that choke you up? Because it's so profound.

what had I been taught that got in the way? What am I missing now? This story was brought to us and reported by Jennifer Brandel. And before we go, we should say that Jen 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 Jen, can you just give like a cliff's note? 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, like, might we be missing analogous things in society? Yeah.

Does that make sense? Not quite. Say one more beat. Say one more beat. What does that mean? An interstitium in society. Yeah. 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 and like... Like a kind of work. 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. 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. Yeah.

Yeah. Yeah, it's really. Oh, well, thanks. 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. 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 Theis, Dr. Neil Theis 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 Thiess.

This episode was produced by Matthew Kilty with production help from Akedi Foster-Keys, mixing help from Arianne Wack, fact-checking by Natalie Middleton, who was edited by Alex Neeson. Big special thanks to Jessica Clark, Aaron Wickenden, Mada Zapata, Daryl 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.

Oh, and before we go, I guess we should just sign off with what happened after Jen 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 as I said, she just went home, drank some tea. 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 going to make my pee green. We're going to see. I have not...

urinated since um well for a while since the dye was injected so let's see here goes take a look whoa oh wow it's like highlighter yellow green it's really um 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

Thank you.

Matt Kielty, Annie McEwen, Alex Neeson, Alyssa Jong-Perry, Sara Khari, Sarah Sambach, Arianne Wack, Pat Walters, and Molly Webster. With help from Timmy Broderick. Our fact checkers are Diane Kelly, Emily Krieger, and Natalie Middleton.

Hi, my name is 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, the Simons Foundation Initiative, and the John Templeton Foundation. Foundational support for Radiolab was provided by the Alfred P. Sloan Foundation.

On Notes from America, we have conversations with people across the country about how we can truly become the nation that we claim to be. Each week, we talk about race, our politics, education, relationships, usually all of them, because everything's connected. And you, our listeners, are at the center of those conversations. I'm Kai Wright. Join me on Notes from America, wherever you get your podcasts.