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Listening.

To.

Radiolab. Radiolab. From W. N. Weiss.

C. C? Yeah. This is RadioLab.

I'm Lulu Miller.

I'm Latif Nassar.

Oh.

Hello. Along with reporter, Jen Brandel. Hi. Latif, Jen, have you guys met?

I don't think so. I don't think so.

No. But we have a friend. 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. Is right. I'm an annoying person to talk to at a cocktail party because I can't really say it distinctly. 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 begin? Are you ready for a journey? Yeah. Okay, so we're going to just to.

Kick it off. Caffinated, baguaged, ready.

To go. We are going to start inside a hospital. What? Fourth? On the fourth floor. Fourth floor, going up. Jenna and I are walking around to 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.

This is Lulu, this is Jen. Hi. We have permission to.

Be here. 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. Anyway, these doctors, they're pulling out Tupperwares and one by one, they are lifting the lids and pulling out, whoa, human organs.

Oh! That's small intestine coming here.

Organes I've heard about but never seen before.

And this is.

The pancreas. They pulled out a whole stomach. It's just like a big.

Orangey red chunk of meat. And they pulled.

Out-here's the dome of the uterus.

Oh, wow.

My uterus? This is your ovary? 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 it 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.

This is your stomach. 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.

Oh, so are you on pancreas today?

And so what that room 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.

Coming down from the operating room all day, hundreds of.

Specimens of the day. Because maybe that person is getting a transplant or maybe they had- And what is that?

That's.

Cancer. -a tumor removed. Wow, that's a big, that's like a.

Tennis ball of blood.

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 a - We are giving.

Consent for this procedure. I am giving consent.

Consent. I had given consent. I just tested the syringe. A couple of drops came out. Here comes the big needle. -inside the human body that scientists had - There it is. Is. 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.

I'm... Wow. All this time inside of all of us.

An organ?

Yeah. Well, a body part. A big deal body part.

A big deal.

Body part. A big deal body part that we missed.

Until five years ago. 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 tell how we missed it.

No, people have looking at the human body 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 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 its namewhat it might be why we we it, how knowing about it might change our lives, our health, and maybe even society a little bit. Really? But I'm going to pipe down because, because, is going to tell you.

The rest. All right. Oh, great. Great. I just had a Google meeting pop up. Let me just kill all these things. Stop it. It.

Okay, your 17 other jobs that you.

You.

Yeah, exactly.

Okay. All right. Okay. So the story starts with this guy, Neil Neil Hello. Hey, Neil. How are you doing? Doing? I'm Neil.

Neil I'm good.

Okay, let me... So Neil was actually one of the doctors.

So this is Lulu, this is is Jen.

Hi. Is showing us around the lab. Okay. He's a short, muscly fellow. He's got tattoos on his arms. And he's an't 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 all over.

The map. The classic Rabbi programmer.

No, exactly. Exactly. Yeah, yeah, yeah. Yeah.

But about why did you want to become a doctor in the first place? Sorry, I know this could be a long story, but quickly, in summation.

I was 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 formula was going to get get I'll never get get I'm never going to have have kids, I'll be doing Hitler's job for him because of that. I'm going to grow old and die alone.

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? 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.

In Connecticut- died of a heart attack on the golf course that morning. The funeral was going to be the next day. So she called me after the the funeral, I said, How was Dr. Robinson's funeral? And she said, It was just amazing. All of Hartford came out for his funeral. I thought, Oh, if you're a doctor, people come to your funeral. That's why I went to medical school.

Wait, so most.

People go into medicine because they care about other people, or they say say that, but you because you wanted people to care about about.

Yeah, basically. I was terrified of being alone, and I I 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. School. Discovered pathology in the middle of it and was like, Oh, I like this.

Which is funny because in.

Pathology- pathology- 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 actual people 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 slides here. Taking an organ and making a tiny.

Cut off very, very thin slice.

Slice. Sample of it, putting it on a slide, adding some stains to it to give.

It color. Then we'll look at it under the microscope. Where he'll see-a pattern of of colors, my God. God. Between the shapes.

Okay.

Wow. Each cell has a particular shape. The The stain here is the blood vessel lining cells, like a stained glass. This is an artery and this is a vein. The teal are greenish color. These white spaces here, and this is fat. And so you see how that looks blue? Yeah. I sit down at my microscope and I look at the slides. I know that's a bad sign. Can I make.

Make He ends up becoming a liver pathologist and a world-renowned one at that. But he's also super accessible and friendly. Even though he's not working directly with patients, he has a lot of meaningful relationships with with 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.

He had this cush job at.

Beth Israel. It was very luxurious. I had my own room with a multiheaded multiheaded microscope.

From all the actions so he could focus on his microscope all day long.

Long. And colleague walks in one day.

David Carlok.

Neil told us you are a scope jockey.

He would would say Do you know what that means?

Is that a.

Term of art? No, no, it's very derogatory.

Is it like a dig of someone who likes looking at.

At No, no, no, no. An endoscope.

Oh.

Endoscope.

Oh, okay. 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. No, it's probably more like, Excuse me, Dr.

Thees. We've got this new new Until now, gastroenterologists were often.

In the the A very fancy fancy endoscope.

It's a miniature miniature microscope. You to see what you've been missing so far. You can see cells in a living living With real-time microscopic microscopic critical to their their decision process. Process. And was showing us something that we didn't understand.

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

I'd.

Call it more more A dried dried Ziti. Little mini mini.

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? Again?

So 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 YTS of their eyes are yellow or maybe their skin is is.

One of the causes of problems like that is a narrowing in the bile duct, which could be benign or could be cancerous.

So the patient gets sent to.

David Zawar. And then we give the patient an injection of something something called is is fluoroxine.

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. Then after the shot, David grabs his fancy scope.

It just looks like a big black hose.

It's about as.

Thick as your finger. With a flashlight at the end.

End.

Then.

Threads the the Down the esophagus.

Past the the stomach.

The small small intestine. Into the.

Bile duct. 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 honeycomb appearance.

Where they'd always seen just like a dark wall. There were now these glowing holes where the fluorescent was showing with these little dark fibers.

Around them. Them. And nice regular honeycomb shape.

This is in patients who who have 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?

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? 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, mean, says, 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. Well, there's some really important piece here that will make sense of it. Just what is it and how do you find it out?

Out? Neil took these images of the honeycomb.

I couldn't find them in.

Any textbook. Textbook. And would show them to colleagues on his lunch break.

Break. And were.

Making fun of me. They were like, Neil, he's just wild about about People just.

Didn't really care. Yeah. 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 a 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 into wax 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.

They'll They'll us a slide of the bile dung.

Dung. You see all these cracks?

Yeah. You see all these faint little.

Cracks in the the 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. 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.

Spaces. Were what was left behind when the holes of this honeycomb dried out and would collapse on itself. It's like, have you seen those tiny little sponge that are dehydrated? And then you put them in water and they go.

Like, boom. The ones that are shaped like a dinosaur or or.

Something like The ones that are like a pellet and.

Then it's like, whoa, a dinosaur. Yeah. Yeah. So can think about the way that slides have been being made for a hundred years, like the pellet. That's what they've been looking at. But with with David's they were seeing the pellet expanded into the sponge sponge full of holes, which is how the walls around around a living bile duct actually look.

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

Which, you know...

Who cares about the bile duct, right?

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

Big deal.

But this is where it gets interesting.

So within.

Within Neil is back to doing clinical work.

And he started to look at tissues that he sees every every day, now now with new eye.

Eye. So day he got sent to to.

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

So Neil did his thing.

Formaldahide.

Alcohol, wax. Took some of the healthy skin, put it under the microscope, and.

Saw-it had the same cracks. Cracks. So was exciting.

It wasn't just the skin. He was seeing those cracks in the collagen, around the stomach, around the colon. There are cracks. Tiny little cracks.

In a dense wall. It's not just the bile duct. Duct. Okay, 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 dry it 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? We injected my vein with the dye, fluorescent.

David just took the scope. Just holding it. Ran it across Neil's skin.

Scan his skin, and sure enough-.

Is that it? Are we looking at it right now? That's That's it, Wow.

There it was. The white spaces are fluorescent.

Fluorescent. Like 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.

Really?

They sculpted you? Yeah, it was the.

Coolest coolest thing.

And saw the honeycomb fluid thing?

Exactly. They could see it in me 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. 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.

Question. You know, it's what is it?

What is this structure they'd never noticed before? Yeah.

Okay. They phone.

A.

Friend. Becky Wells. Professor of Medicine at the University of Pennsylvania.

Becky does a lot of research into how organs hold their structure and their shape. Shape.

So body is 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 can't just have a little layer of cells floating around in the middle of the abdominal cavity. Things would would leak out. Would be very unstable. It would be very fragile. So the bile duct actually has layers of collagen to keep the bile duct together.

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

Exactly. 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.

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.

We sat at this microscope in this completely.

Dark room. They turned.

It on. What we could see was it was almost like waves of hair.

Which was the collagen. But now in in they could see it was actually like a network of tubes.

We just start yelling and and high each other.

Other. Yeah, Why?

Well.

Because as far as Neil.

Could tell- That meant that every collagen layer in the entire entire the dermis, the wrappings of all your muscles and your your the collagen that wraps around every artery and every every 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 and tunnels. Tunnels. And of those tunnels, there was this fluid.

Eventually.

They got a hold of some of the fluid.

It's clear, but a little yellowy.

Like egg YTS. We have a colleague of Neil's analyze it to see.

What's actually in it. 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.

Your skin. Reduces wrinkles.

For younger looking skin.

So when people get injections to plump up their cheeks or whatever, a lot of times it's hyaluronic acid because that 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.

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

There There all all these brown lines-.

-that have this 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.

Everything Throughout the body.

They eventually figured out out 25 of the fluid going through our body is this stuff. What? Yeah, Yeah, 25 of the liquid in our body is flowing through through this. Had no idea what it was or that it existed.

Wait, and what %.

Is blood? We don't know the exact number, but it's less than that. Less than that?

It's four times the amount of blood.

Four times the amount of blood.

Yeah, four times. Times. And sorry.

As you mentioned it like that, because the circulatory system has a heart, which is like pumping stuff through. What's the mechanism of.

Stuff getting- Yeah, and what's the directionality?

And what's the contents of this? Yeah, and why wouldn't it just all settle in your feet or something, that 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 is also expand and contract, expand and contract. Anyway, just a very quick recap. This tissue that everyone thought was was like a wall and totally passive is almost almost 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 a unified system similar to the nervous system or the circulatory system that they had totally missed.

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

They're like, We got to publish.

We got to publish. Now the question is, what do we call it?

They call it the interstitium.

The interstitium?

What comes to mind when you hear that word?

Well, if I'm being honest, if I was making up a fake organ, maybe that's the.

Thing I would call it. Okay, fair enough. But for me, I don't don't I think it's actually really evocative. Maybe because I'm someone who lives my life professionally between many different worlds and ways ways of I like how it evokes spaces that are unseen and in between, but there's still this overarching question. What the fuck is it doing? Fuck, there's that noise. Sorry, in my background, it was my... I had a calendar update.

Come up again. Again. And 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 Lab. My membership provides RadioLab with a steady source of funding so the team can continue to tell stories about our crazy world. And I get access to exclusive live events and bonus content. Join me in supporting the show we love. Sign up up at org/join.

Hey, you all. I'm Riane Riane host of Ariacode. And I'm here to spread the Gospel.

Of Opera. We are all gathered to experience the.

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And unexpected guests to.

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Life one aria at.

A time. Don't miss miss the season of AriaCode.

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Wherever you get podcasts.

Radiolab. 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 five years ago.

Well, not nobody.

Okay, might not be nobody. Okay, we'll 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 tissues that makes up a.

Previously unknown organ. Our interstitium work broke.

And shortly after Neil was.

In in I'm 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, stage, he gives presentation. Presentation. And he's.

Done- A very very high physician in in.

-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? I said, Well, blah, blah, blah. Scientists have expressed skepticism.

That the.

Interstitium.

Is its own organ. 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.

Books may soon 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 find that 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 is Chen. Chen. So professor, Professor Chen, is not a smart ass, and he didn't have the reaction be like, Duh. So we talked to Q-Sheng through the help of a translator.

Wow. I don't.

Even understand.

What it.

Is happening in Chinese. I'm I'm mind So Q-Sheng is a professor at a veterinary school in China. And he does a lot of research on the kidneys of camels- Animal Animal tissue, the of of yaks, And apparently female turtles that can store sperm in their tissue? For up to one year long. What? And they can still be fertilized.

That's wild. Yeah.

But anyway, in 2018, he's on an airplane flying somewhere for work, and he comes across the interstitial paper.

And he suddenly had this memory of being a little boy. He grew up in a rural village in China. One day, he had something that give 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 him acupuncture, and had been given a few needles on his hands, on his legs. Legs. And he instantly felt this relief. He He started It was like... I just started like a.

A farted I'm good.

Like a fart in that sense of this instantaneous. The discomfort just went away. It wasn't actually a fart, but it was a feeling of total relief.

So.

He's on a plane reading about the interstitium, and he was just like, God. It resurfaced that question he'd been carrying in his body since he was that little boy, which was like, How did that work? 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 book Wangdi Nei.

King.

From 2005 years ago. 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 be ethical, he has to do it on animals.

Wait, is animal acupuncture a thing?

Oh, Oh, a Well, I 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? Yeah. She's got arthritis in her hind legs.

And the idea is like the same networks and.

Pathways, is that right? Yeah, pretty much.

Huh, who knew? Okay.

But so... Q-shang got some some rabbits. Twenty-four rabbits? Gave the the rabbits... Collitis. Collitis. It's this disease that affects the lining of the colon. So these they're bleeding, they're having little ulcers, they're losing weight rapidly. They're not doing well. But then he takes these little tiny needles and puts them into the joint around the the rabbits leg, its knee, and the acupuncture works. The inflammation gets better. The bleeding reduces. They start getting weight again. They're better. And some of them are just.

All good. Brand new. Totally Totally Just returned to normal. Yeah. Wow. Wow.

So then he uses the interstitial paper almost.

Like a map to.

See if he can find anything in the interstitial that's happening that could explain this.. And he finds telocytes. Tenocyte. These cells. Oh, Oh, telocytes. Telocytes, yes. Called called 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 cell-to-cell communication or signaling. But what he saw was that in the rabbits who got acupuncture, their telesites were super activated. They were throwing off chemical signals, talking to each other. They were just more active.

The telesites are always there in the interstitium, but at least in these rabbits, when they got acupuncture, they're on hyperdrive?

Fom, foom, foom. Yeah.

I.

Was excited by it. 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. This feels very big. But his answer was basicallyexactly. All I can say is that we found what we found.

I pushed again, asking if he thinks this is still a big big.

And.

He's like, I cannot say that myself. Myself.

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're.

What they- Or exactly what they do.

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 no Western anatomy to explain those clinical impressions, those personal experiences.

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

Very very It provides a cultural bridge to allow people to have these discussions.

Discussions.

Which is exactly what happened with Q-Shang, who said that to him, when Niall and the team found the interstitium, found the body, but they didn't find the soul. They didn't find 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 alongside Western medicine.

My hope is bit by bit, this community will be talking to people in the Chinese medicine community, in the diabetic medicine community, community, Ayurvedic medicine, because we're all talking about the same body.

Okay, I get that. But can I just just I don't know, it feels like we're just learning. And I don't know, it feels like a jump to rope in this whole other ancient tradition of medicine. Medicine. 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. I'm excited about this. Go, Lily.

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 Friedel. I'm a medical doctor.

By training. His name is Peter Friedel. 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. He became a scientist. He left practicing medicine behind and he became.

A- Cancer scientist.

Cancer scientist. Yeah.

He- At the end of the day, I switched from applying knowledge to generating knowledge.

He was curious about basically one of the most fundamental mysteries of cancer, which is how does it metastasize? How does it show up in the skin?

Then at some point, shows up in lung or liver or the brain.

How does it spread?

Yes.

Exactly. All throughout the body. Body.

Yeah, so was was.

Known obviously once cancer gets into the the.

Blood the lymphatic.

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

That's That's It's like harder than you would.

Would Yeah, because even though that might be a tiny little.

Little A couple of microns, maybe millimeters.

Millimeters. The point of view of a cancer cell, 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 that cells.

Come tearing through tissue with, he calls them -bazookas or -bush knives.

-like machetes. -and scissors, all sorts of.

Of scissors get through.

This tissue in.

Order to move-so that they can bushwag their way to a vessel and then to the rest of your body.

This was the premise.

Why was that the premise? Premise?

Well, saw that cancer cells in the petri dish, they cut everything into pieces.

He says you can throw cancer cells and tissue cells into a petri dish.

And come back after the weekend.

The cancer will have ripped up.

That tissue. 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, Okay, that's how it moves through. Through. So do you need to do? You need to disarm the cancer cell. Cell. But turned even if you give medicine to people that takes away away the the bush.

Bush 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.

Was Hundreds of of millions 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.

People took a step back and wondered, okay, what did we get wrong?

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. What he does is he he gets.

These these mice and we take a mouse, cut a little hole.

Into it, into the skin on.

Its side, and build a frame out of plastic into this hole.

Then into that, they put this little piece of.

Glass, the glass of an aquarium, so you can look through this glass into the living tissue.

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 its back.

Underneath a big, huge microscope.

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

Then.

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

It was spectacularly colorful right from the beginning. Beginning.

Imagine the skin tissue of the the mouse.

Blue.

Blue. A blue jungle of skin tissue. Then the cancer cells, they were like these green little dots.

The green dots were moving.

But But surprised surprised was that 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.

Streaming through extensive root like fingers.

Fingers. 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 a highway-type system that the the were exploiting.

What were you thinking in that moment?

Oh, this is interesting. Can we observe it a.

Little longer? You're just 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 he's this a few years before Niels and Becky and David's paper comes out. So he still still doesn't idea of a unified unified that isn't out in the world, but he is seeing the interstitium, the channels of.

The interstitium. So without that information, what did he think? He thought that the cancer cells were making this channel?

No, No, no, no. Can tell that the channels are in in in the skin. So after the transfixed awe.

Wore off. We thought, Holy shit, if every tissue has has.

These How are we ever going to be able to stop the spread of cancer?

There are too many channels. It's endless.

There's just no way.

It's clear we're not going to stop them. Them.

And so years, Peter just sat staring at these cancer cancer moving through these highways, feeling hopeless. Until one day, he was like, What if we forget about about the trying to block them or stop them, and instead just go after the cancer cancer And kill it. What he does is he goes back to these mice and he just blasts the cancer cells with radiation. What he discovers is that the only cells that survive the.

The blast what we call the marathon runners.

Are the cells that are running through the interstitium. Peter starts pulling these cancer cells out.

Of the the To find what makes the marathon runner special, different from.

The rest. What he finds is that these marathon marathon.

Runners, are a smart, opportunistic creatures.

Rather than deploying deploying these to rip through tissue, they have these little claws that they use to get into the interstitium and move through it. They can also use the claws to fuel up in a way that makes them grow bigger and stronger and.

Harder to kill. That's already bad bad news. It also is is good because if you now know what makes them special, you can take it away.

Fast forward, Peter develops these antibodies that basically de-claw the cancer cancer cells. Gives these antibodies to the mice.

You give radiation therapy at the same time, the marathon runners melt away and they die. We can cure the mice even in tumors that otherwise are not curable. 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 ten mice were clean. That means we didn't need to block the roads. We bombarded the cars in a good way.

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're not targeting the the sick own immune system.

I'm finding myself getting emotional about this. Why? Because my my passed away from cancer, from lymphatic leukemia and lymphoma, which are system wide. That means they've gone through the the whole, everywhere. And she got got chemo she had too many white blood cells and the chemo, they were too aggressive with with and they knocked out so many white blood cells. 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. They over shot it. Oh, my God.

Oh, my God. God. Is that Because I know she lived with it for a long time.

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

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 of a initially proposed strategies will make it to the patient. We will have to see.

You'll have to go through years of development of trials in humans.

But at least proof of concept we made.

We delivered. That's what feels big because what Peter was finding in mice.

Tissues. This is a slide.

Of breast. Neil and Becky are now seeing.

In humans. Humans. Here cancer cells walking along through the interstitium like they've got a nice little path to follow through the woods. Oh, my God. Here they they just marching from the interstitium to get to the lymph nodes.

Yeah. So, Neil and Becky, I think of them as like these cartographers where they're essentially trying to make.

These maps- Of every single organ.

-of 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. It's like they are publishing as fast as.

They can. We've got six papers that are heading their way towards publications.

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. Will. So people are interested in acupuncture, pick 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 there's a lot of bacteria in the mouth, right? But we don't know. I mean, it's wide open right now.

It's just amazing to think this little microscope goes into the body and then opens up this whole new realm that we're just beginning to learn about. This is my favorite 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?

Now, what I'm going to show show you... We have as I said, we cut open the small intestine and the wall of the stomach.

Now, this is the wildest part of the story for me. When we were in the lab with with at one point, he takes a cross-section of the small intestine in in his And.

You.

See this- this- he started pulling at this.

Thin- -that looks.

Looks -layer of almost translucent threads encasing the intestine.

That is the interstitium?

That's the interstitium. What?

Yeah. But that was it. That is it.

Is it okay to get that.

This close? Yeah.

See, like here, when I pull it, you see little threads getting tense inside there? Yeah. They're like- That's the interstitium.

Wow. Yeah. Is like, Wow. I thought this was like a technology.

No, no, no.

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.

What Neil said was like, like, one had put it it together we've been told to.

Discount it. 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 have decided that this this stuff that we were seeing in the body, it just didn't matter. It didn't do.

Anything important. Yeah, 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.

Med This is nothing we even have to pay.

Attention to. To. The cracks in the tissue, they don't matter. Don't worry about the cracks.

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, is this actually a story just about beliefs getting in the way?

Beliefs and training and and dogma. Comes back to the San Diego Suzuki-Roshi, who was the founder of San Francisco's Ed Center, said that in the mind of the beginner, there are many possibilities. In the mind of the expert, there are a few. I get choked up.

Why does that took you up?

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

The story was brought to us and reported by Jennifer Brandel. Before we go, we should say that Jen has one more more 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 a CliffsNotes?

Sure. Yeah. I mean, truth be told, I'm most interested in the interstitium's metaphorical value. Value. Like, 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?

Not quite... Wait, say one more B. Say one more more beat. Say one more What does that mean? An interstitium in society.

What does that mean? Just briefly. I mentioned at the top, I'm a person who operates between different organs in society, or as we call them, organizations between journalism, tech, government, democracy. In learning about the interstitium, it was like the skeleton key for me that made me realize that there's this whole invisible thing that has been discounted. The people, the the that do this connective work and like -.

Like a work, almost.

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

Yeah. I guess I just want to hype you now. 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 really Yeah.

It's really need. Oh, well, thanks, Lily. 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 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, Dr. Neil Neil 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 on by Dr. Neil Neil This episode was produced by Matthew Matthew with production help from a Ketty, Ketty, Foster mixing help from Arianne Wack. Fact-checking by Natalie Middleton, who was edited by Alex Alex Neason. Big thanks to Jessica Clark, Aaron Wickindon, Mada Zapeda, Darryl Holiday, Dr. Amy Chang, Kate Sassun, Guy Huntley, John Jacobson, The Village Zendo, Scottie G, and rest in peace to Mavis, the 14-year-old dog. 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 instead, she just went home, drank some tea.

I'm just getting back to the the I'm staying at in Brooklyn. 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… Well, for a while since the dye was injected. Injected.

All see here goes. Okay, let's take a look.

Let's take a look.

Whoa.

Oh, Oh, wow. It's like highlight or yellow-green. It's really… it's like eyeliner yellow-green. It's really like neon greeny yellow. It's wild. Okay, I'm going to take a a photo. This what we get to do for work. What a privilege.

Radiolab was created by by Jad, and is edited by by Wheeler. Wheeler. Lulu, and Latif Nassar are our co-hosts. Dylan Keith is our our of of sound design. Includes Simon Adler, Jeremy Bloom, Becka Bresler, Bresler, Foster-Kays, W. Harry Fortuna, David Gable, Maria Paz-Gutierrez, Sandu Sandu Matt Kielty, Annie McEwen, Alex Alex Neeson, John-Perry, Sara Kari, Sara Sara Sambak, Wack, Pat Walters, and Molly Webster. With help from Timmy Broderick, our our fact are Diane Kelly, Emily Emily 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 Simmons Foundation Initiative, and the John Templeton Foundation. Foundational support for RadioLab was provided by the Alfred P. Sloan Foundation.