Radiolab - Mortality

Episode Date: June 14, 2007

This hour of Radiolab: is death a disease that can be cured?

You're listening to Radio Lab. From New York Public Radio. Public Radio WNYC. And NPR. I'm Chad Abumrod. And I'm Robert Crilwich. And this is Radio Lab. You ever wondered why it is that all living things die?

I do wonder about that, actually. Which keeps me up at night. Which always leads me to the next question. Do we have to? Do I have to? The topic of our show. As a matter of fact, and the natural place to begin, to look for an answer, is in a garage. So here we are in your garage.

Here we are in my garage. The owner of this particular garage is one Leonard Hayflick. He is a biologist. He takes me to the corner where he's got this... Describe what we're looking at here. Well, what we're looking at is a barrel-shaped device. It's a metal canister that is shaped kind of like a thermos, except bigger. Opening the lid.

He twists off the top and... Wooosh. Wow, look at that. Out comes all of this smoke. Dry ice from Halloween is what it looks like. Well, this liquid nitrogen is used in a lot of movies. He reaches his hand into the liquid nitrogen fog, right into the bowels of this canister and pulls out.

And this is what I'd come to see. Those are what we call... What? Some test tubes. Tobs in which these anps are kept. Admittedly, they're not much to look at, but if you know what's in there, it's almost holy. Each tube has millions of frozen human cells in there. And these cells have completely changed how we think about mortality and immortality.

And you keep it in your garage. Yes. Why? I mean, I think it's pretty cool, but why? Because nobody else think of looking here. Oh, okay. Well, I certainly won't divulge your address or anything. No, please, don't tell anybody.

No, of course I wouldn't. but it's in California, is all I'll say. Well, where else would you want me to put it in my bedroom? Oh, I don't know. I mean, it's, I imagine something like this you would find it in the middle. It started for Leonard Hayflick about 50 years ago. I got the backstory, actually not in California, in Philly. Soundcheck.

Do you want to tell me where we are? Well, we're sitting on the 12th floor of the William Penn House in Philadelphia, Pennsylvania, which happens to be my mother's apartment, who has just celebrated her 100th birthday. Just that day, appropriately enough. In any case, let's rewind to the 50s. Biology was facing a problem, basic problem. How do you study human cells?

Cells are us. It is what we are. But you can't exactly put a microscope up to your wrist. Well, you know, I guess you could. I wouldn't say it's impossible, but it's certainly highly impractical. What you can do instead, and Hayflick was among the first to perfect this, is... Well, he explained it to me. If I take a tiny biopsy from any part of your anatomy that you're willing to surrender to me.

Like, say, a fleck of my wrist. Your wrist. A flick on your wrist. Anywhere you want, the tip of your nose, the tip of your toe. I don't care where it is. And then you raise a pyramid of skin by grabbing onto the tip of a hair. Pull it up. And then with the other hand, you take a sterile scalpel and whack the tip of that pyramid of skin off.

And I drop it into a test tube. And I introduce an enzyme preparation called Tripsin. And that material dissolves the cement that holds all the cells together. Think of your tissue as a brick wall. And once I drop that brick wall into my test tube, I need to dissolve the mortar. Right. And now I have your individual cells. And if I feed them and treat them nicely, they will divide.

Each cell will produce two cells. Each cell will produce two cells. Two cells. Two cells. If you do the math, you'll find that they'll cover the city of New York in about three weeks. I mean, you know, that's if you had a big enough petri dish. In any case, this process, it's called cell culturing, is the simplest thing in the world these days. I mean, modern biologists can do it with their eyes closed.

But back in Hayflicks Day, in the 50s, it was very fuzzy. Because no one really understood the mechanics of it. No one knew exactly what a cell liked or what it didn't like. And so the people that were really good at getting the cells to divide from two into four and eight and sixteen, whatever, they was like they had the touch. They had what was called a green thumb. There was a mystique about them. Because, you know, don't forget, this was the early days. Biology at that time was still kind of a black art.

Well, I'm interested to use the term black art because you're, you know, you're not. That attribute was given to the field by a single individual who dominated the field for about 20 or 30 years. His name was Alexis Correll. He believed that the contamination of tissue cultures with airborne bacteria could be eliminated or prevented by maintaining sterile circumstances that in his mind included everything being painted black.

Now don't ask me that rational... me the rationale for that because I can't explain it. That's so Gothic. I love it. Exactly. All of his technicians and he himself were dressed from head to foot in black. And he had a gallery around the lab where reporters could wander to see these mystical black figures roaming the laboratory floor, doing strange things with strange implements, and ending up with cells growing. It must have seemed like wishcraft.

It didn't seem like. They believed it was witchcraft, especially because Alexis Corel claimed to have kept a chick heart alive for 46 years. A chick heart? Yes. Like the heart of a baby chicken? It was a fragment of tissue from the chick heart. So for 46 years, the cells divided and divided every couple days? That's what was alleged.

Now, 46 years is a long time, right? Yeah, I'll say. And so scientists thought that if they've gone this long, they'll probably go. go forever. Because of Corell and a couple other scientists, it was thought that cells are immortal. Under the proper conditions, they'll grow indefinitely. And Corel's little chicken heart seemed to be proof of this. It just kept spewing new cells, which he'd keep dividing into new bottles.

As the New York Post said, quote, if all of the cells produced by Dr. Corell from his cultured chicken heart were kept together, they would probably. produce a rooster that could cross the Atlantic Ocean in a single stride. End quote. I wish I'd come up with that myself. Was that a quote that was made lovingly or admiringly, or was that a sort of sneering quote? It was made to sell the New York Post. But did people bought it, I guess, is what I'm asking.

You're darn right they bought it until it was torpedo. By me. Right. Well, that's the story that I want to get to next. It happened by accident. He did not set out to torpedo the rooster or the whole idea of cellular immortality. It just kind of happened.

He was in the lab. It was the 50s. He was just a kid. And he becomes worried. This was an ordinary worry at the time that his little cells would become contaminated. I knew at the time that if you cultured normal human tissue from adults, you might grow simultaneously unwanted viruses.

Because in adults, the viruses would sometimes sneak into the cells and hide there. And I didn't want, of course, my cultures to be contaminated with these viruses. So I zeroed in on human fetal tissue. Human fetal tissue, as in from abortions. Sorry to ask an ignorant question, but abortion at that time was, was it anything like the crazy political Thornbush that is now? No. Far more rational.

It was actually quite easy, he says. He just picked up the phone. called my friends at the University of Pennsylvania and said I wanted fetuses whenever they were surgically aborted. And as you might expect, when you put your order in for fetal tissue, you know not when the phone will ring. He never knew when the shipments would arrive. I would receive maybe one fetus one week and then two weeks later another one. And so to keep track of things, and this turns out to be key, he kept a log. Every time he'd get a new shipment, he would jot down the arrival day and then,

dropped the cells into the flask, watch them divide, do the whole deal, and then every couple weeks he would come and check on them. And that's when it started. I began to realize that some of the cultures are unhappy to stop dividing. At first it was just one. One batch. What were you thinking at this point? I didn't know what to think. Because it was just an observation and it was just one batch. Batch A, let's call it. All right, no biggie. I'll see how it goes. Come back and a month later I find out that not only A is still not doing its thing, but B and C aren't either. Now three batches of cells had gone kaput. I said to myself, well, that's peculiar.

Peculiar because here he'd done the same with these cells as he'd done with all the others. He put him in the same glasses, same solution. Same conditions. Didn't add up. Now I have to find out what the cause is. So go back and look at my records. And that is when it smacks him in the face. What?

The thing that all three batches of cells hadn't come in, and he knew this because he'd kept the logs, is that they were the oldest. So to speak, he'd received each batch of fetal tissue from the hospital. I received it from the hospital. Roughly? Nine months ago. At nine months or thereabouts, they just kind of hit a wall,

and they stopped dividing. But the ones received one month, two, one, three, one, four, and five months ago. Those cells were doing just fine. Perfect, beautiful. And he kept seeing this. Simultaneously, two thoughts enter his mind. Thought number one, this can't be an accident. If it was an accident, it should be random.

Uh-uh. Thought number two. Wait a second. This has to be an accident. Because I had been taught by experts. Its cells are immortal. They will grow forever. All right, fast forward a few months.

Those two conflicting thoughts are still fighting it out in Hayflick's mind. Along comes the annual. biology conference. The biggest scientific meeting in the world. At that time, the meeting was held in Atlantic City. Hayflick and a few friends decided to hop in a car and crashed the meeting because the featured speaker was a guy Hayflick really admired, guy by the name of Ted Puck.

I want to hear what he has to say, and I'm going to, if I can get enough guts, I'm going to ask him a question. I remember it distinctly. It was a big hall, you know, like a thousand people. I'm sure it's an exaggeration, but it's huge or lots of people. And I'm somewhere in a little listening to his talk. You see, the methods previously developed, whereby single cells... And at the end, as is customary, you ask for questions.

Are there any questions? I timidly raised my hand. So, yes, the young fellow in the center, yeah, you... Yes. And I ask him the following question, Dr. Puck. Have you ever found that the cells that you culture stop dividing? Did you want to give him a kind of... Gotcha. What were you thinking?

No, I was ready to publish. I wanted to know whether I'm in trouble, whether I have an artifact on my hands that nobody has seen because they'd do it right. I see. I'm still worried. Got it. And so he says, he looks at me and I'm like, you're an idiot. Well, of course. The cells stop dividing occasionally.

Of course, I lose my cells occasionally, but I simply go back to the freezer and re-conciled. Meaning that when the cells stopped dividing, which he just admitted they do all the time, he just said, eh, something happened, I don't know what, I'll just go back to the freezer and get more. Well, that's not right, because if they stopped dividing, they might have just died. It's not that he was cheating, it's that he thought he had screwed up. Oh, then I knew it was a gotcha? Well, he didn't yell gotcha right at that moment. He just sat back down.

But now he knew it was real, because even the brilliant Ted Puck had seen it too. But like everyone else, for the past 60 years, he just hadn't recognized. for what it was. I imagine in labs all over the country, there must have been a lot of moments when cells stopped dividing. And at every one of those moments, you're saying, the thought that popped into the technician's mind is, I f*** up.

Absolutely. That seems like a crazy kind of mass delusion. It's called dogma. You know the definition of the word dogma? I've heard that word before. That's it. The concept of mortality was absent from people. people's minds.

Well, wait, if they didn't understand the idea of mortality, then how did the scientists explain getting older and moving towards death? Pre-torpedoing? Yeah. Radiation? What? Radiation. What it means?

No, seriously. I mean, it was this idea that stuff is happening outside the cell, that radiation is bombarding the cell, like gamma rays and alpha rays and these kinds of things. And that somehow ages the cell. So the trigger is outside the being, not inside the cell? Right. And so my discovery, and I pointed it out in that first paper, was to indicate that it's in the cell, not outside the cell.

That's where the action is. Hayflick argued that somewhere in the cell, there's a counter. One, two, three, three, three, four, five, six, keeping track. Because after about nine months of happy dividing in a petri dish, when the cell gets to 50 divisions, sometimes a few takes more, a few ticks less, but 50 is the average, and when it reaches 50,

a little counter inside the cell, 409, 50 says, Stop! 50 is the magic number. Where did this number 50 come from? You'll have to ask God that question. Nonetheless, Hayflick, not God, has his name forever attached to that number,

because it's become known as the Hayflick limit. Now, one of the interesting things Hayflick told me, while we looked at his secret stash of fetal cells in his garage, is that there is a way to tinker with the cellular counter. If you lower the temperature by, say, putting the cells in liquid nitrogen as he has, the dividing will get slower, two, and slower, and slower, until it stops. At 250 degrees below zero, the cells will not divide, and they won't die.

They'll just wait for as long as you keep them frozen. The cells I have in my freezer have been frozen for 44 years. Does that make them the longest? These cells are the longest frozen normal human cells in the world. The fetal cells he's talking about, incidentally, are the ones that he used to discover the hayflick limit. He calls it W.I.38. What do we know about the mother of the fetus that created W.I.30? She was a Swedish woman, and she wanted an abortion because she had many children and was very poor.

Her husband was not a good father, and that's where this tissue came from. Here's the kicker. After the Hayflick limit experiments, these cells, this particular strain, was used to incubate and produce vaccines. All different kinds. Polio, German measles, measles, mumps, rabies. And anybody born in the last 50 years who's had any of these vaccines has had these cells in their body? The numbers of people who have benefited from these vaccines now exceed one billion people. That's billion with a bee.

That's billion with a bee. Wow. One aborted child creates a fleet of cells that vaccinate a billion people. Think about that for a second. And is it true that you have a cell line from, is it your daughter? Yes. Yes, I also have cells in there from the amnion of my daughter, Susan Hayflick. Do you keep them for purely scientific reasons, or is it sort of like stamp collecting you have them as...

Well, it would be... He's a scientist now herself, and so I'll probably give the ampules to her so she can do with them what she wishes. But you keep them because it's your daughter, mostly. Yes, mostly, yeah, sure. That's really sweet. Here's the interesting thing, scientifically. If you were to warm these cells up, give them some food. They'd start to divide again.

Five, six, seven, seven, eight, right where they left off. And even if you froze them again, at say the 16th doubling. 16. And kept them that way for a thousand million years. Wouldn't matter. Because as soon as you unfroze them, off they'd go. On their way to 50. Without missing a beat.

What does that tell you? Tells you that cells remember. They have a memory. Somehow, the cell always remembers where it is in the count to 50. Cells can't count. How do they do that? Well, that was the next big question. So we set about to do a number of experiments.

However, the next big breakthrough came in 1971 and not by Hayflick. While he was doing his experiments in Philly halfway across the world, the very same moment. A Russian named Alexia Levnikov was attending a lecture about Hayflik's research, and he left that lecture puzzled by this question that you asked. How do the cells remember? And when he, have you ever been to Moscow? Mm-hmm. Well, anyhow, so he entered a Moscow subway station.

Went down to the railroad platform. And suddenly he had an insight. He had a brilliant insight when he looked at the railroad track. The first thing he thought was, those tracks look a lot like DNA. If you take railroad tracks and you twist them, you've got DNA. Okay, say it's some DNA, and that DNA's job is to count to 50 and then yell Stop!

Well, we know part of the DNA has the job of yelling, but the other stuff, the rest of it. What if it's just a long sequence of nonsense? Nonsense. What if every time that cellular copier comes along to copy the cell? You lose one little piece of it. The nonsense, I mean. Well, if you had, say, 50 pieces of nonsense as a buffer

around the sense part, the switch, well, then it would take 50 copies to sniff away. all the nonsense until you're left with the switch, which would turn on, and tell the cell to stop dividing. Back in Philadelphia, as we were wrapping up that first interview, a question occurred to me, if we kind of understand how that off switch works, shouldn't we theoretically be able to figure out how to tinker with when the switch gets switched? In theory, I suppose you could, yeah, sure. And wouldn't that allow us to have a longer amount of cell divisions? Well, that certainly doesn't violate any knowledge about this system.

Of course. And wouldn't that theoretically give us something, whether it be extended life or something? Yes, certainly. Hey, Flick had clearly been asked this question a million times. And he patiently explained to me that there is a way right now that we can tinker with the timing of the switch. You take an enzyme called telomerase. Throw it into the mix. And every time that cell gets copied and loses pieces of track, the telomerase enzyme comes along.

And it adds them back on. and maintains the length constant. That way the track is always long. The stop switch never gets switched, and the cell can keep going and going and going. That's how they become immortal. So you're now going to tell me, well, let's inoculate everybody with telomerase.

Yeah. And? Well, if you volunteer, we'll have a shot at it. Are you ready? There must be if I were to go out and shout from your balcony right here. I'm sure I'd get 100 people who'd want to try it. Really? Not after I tell you what you still don't know.

What's that? 95% of all tumors contain telomerase, which normal cells do not contain. The single most distinguishing criteria between normal and cancer cells known today is that fact. So the trade-off for cellular immortality, at least in this case, is cancer. But here's the weird thing. If you look around, you will see that our hayflick limit of 50, is not the only one. We do know that if you look at the normal cells of a Galapagos tortoise,

which has been reported in the literature, they undergo about 125 doublings, if I remember correctly. So their Hayflick number is 125, and ours is 50? Apparently, yes. Does that correlate to the Galapagos turtle living twice as long? Well, it seems to, but that comparison may be anecdotal and not universal. That's what Hayflick is up to these days. He's become fascinated by animals who age differently than us,

who might have a doubling limit of, you know, 200, 500, or no limit at all. There are a whole class of animals that don't age. Like what? The American lobster. The lobster doesn't age? It either does not age or the rate is so slow we can't measure it. I don't even know how to imagine that. What does that mean?

Well, what it means is that the animal gets bigger and bigger. Just growth? Yes. There are lobsters that have been found. Recently, I read about one that's over 50 pounds. I looked it up. The largest lobster ever reported was close to, yes, 50 pounds found in the 1950s just off the coast of New Jersey. Hey, New Jersey.

How old is a 50-pound lobster? Who else? When an indication, it was wearing a Grover Cleveland for President button, so it's very old. I'm Chad I'm Robert Krollwitch. This is Radio Lab. We'll be right back. My name is Ayushu Shrivastava, and I'm calling from the University of Chicago. Radio Lab is supported in part by the National Science Foundation,

and by the Alfred P. Sloan Foundation, enhancing public understanding of science and technology in the modern world. More information about Sloan at www. www.org. Ready? But what am I supposed to do? I don't have to do anything, right? This is Radio Lab. I'm Chadabumran. And I'm Robert Krollwich. And today we're talking about aging. Yep.

Do you even wonder why it is that human beings live, like, how long do we live? About 70-ish, something like that. Yeah, so why 70? As opposed to... Seven. Or like 700? Why that number? Well, that's a good question.

Because apparently every creature has, for some reason, a sort of natural range. So you want to hear a very cool one? How about a rat? Got a rat in your head? Yeah. And a squirrel. The rat and the squirrel. Here you have two animals.

People call, I have friends who call squirrels tree rats. That's Cynthia Kenyon from the University of California, San Francisco. I recently paid her a visit. You know, so in other words, they're very similar to each other. They're rodents, but a rat has a three-year lifespan, whereas a squirrel has a 25-year lifespan. And no one knows why, really. There are theories, but no one has.

really knows why. I got the idea that maybe somehow lifespan was evolvable in the sense that there might be genes in the animal, which when change, allow big leaps in lifespan to take place. So you figured you could just hunt the genes down? Exactly. And this is exactly what she seems to have done. But not with rats and squirrels? With what? Why don't I show you the incubator where we keep all the worms? With worms? Come with me. Little round worms, yes. Called C. elegans. You can't see them with a naked eye. They're just a little speck. But when you put them under a microscope, you see how beautiful they are. So first I'm showing

you here the normal worm when it's a young adult. And what you can see is it's very active and it's healthy looking. So we're looking at this dish, and in the dish is this worm. It's a wiggler. It moves really nicely. Okay. Now let's fast forward

two weeks. Then she showed us a different set of worms in a different dish. These worms were 13 days old. Day 13 of adulthood. They only live to 14. Just live two weeks. They're at the very, very end of their lives. And what we see here is a dead one, so one has already died.

And another one that's clearly in the nursing home, just lying still, not moving at all, and you can tell immediately that it's old. It looks kind of wrinkled and lethargic, and even if you've never seen a worm, ever, you can tell that one is old. So there you got it. You got a young worm, you have an old worm.

Essentially what Cynthia Kenyon is trying to do is she's trying to hunt down the gene that could turn that old worm backwards in time and make it look like a young worm. The worms have about 20,000 genes. So the idea is really simple. You just go and change genes at random, one by one. One at a time.

And see whether any of these gene changes can extend lifespan. How long did it take you to bump into a good one? Well, we actually were really lucky to find a gene pretty quickly. And we found that if we change this one gene called DAF2, if we change this one gene called DAF2, then the worms live twice as long as they normally would. Just like that, and pretty much by sheer luck,

she'd taken this worm and stretched its lifespan for 14 days all the way out to about 28 days. Just 28? Yeah, it doesn't sound like a lot to you, but to a worm, that's double. Boy, can you tell me, like, when you ran into it, did you do a little war dance around the laboratory? Yeah, it was amazing.

I mean, it was incredible. I had a person in my lab who said, Daff 2 is magic, and she's right. Okay, I'm going to show you these magic worms, which are exactly the same as the normal worms, except that we've changed one gene, the Daph 2 gene. So remember that old wrinkly worm that we saw before? Yeah.

The worm she's about to show me is the same age as a 13-day-old, really old worm. Okay, and it's bolting into the picture here. It looks young. It's moving. It's very healthy. It's active. And actually, if you take a microscope, then you look at the tissues. What you see is the tissues of the worm look young.

If you just look at that, you just sit there and you just look at it and look at it and just let it sink in what it means, it's really amazing. It's really very deep and fundamental. You're looking at something that I guess wasn't supposed to happen in some funny way. They were supposed to die. Sure, what exactly is this gene doing to make them live longer? Well, maybe sure, you should ask the question, different way because the worms that lived longer, they didn't actually have this working gene.

Right. When we make a mutation in the DAF2 gene, we damage it. It actually causes it not to work as well. So that actually is kind of profound. That tells you right away that the worm has a gene in it that's shortening the worm's lifespan. Which is why she calls it. The grim reaper gene. The grim reaper gene. It's the gene that makes you die. If you're a worm. Right. So by damaging this gene, Cynthia and her team essentially are taking the Grim Reaper and knocking his knees out.

Stop that! Okay, so the question is, what exactly is the DAF2 doing to make the cell age more quickly? Here's where the story gets a little weird. Well, we found another gene. Hello. His name is also DAF, but it's a different DAF. It's called DAF 16. Dat 16.

And this is a gene whose normal function is to keep you young. It's like a fountain of youth gene. Yeah! So, wait, there was a grim reaper gene before. Right. And now there's a fountain of youth gene? That's what she discovered. And inside the worms, these genes are struggling with each other.

Here's how it works when a worm ages normally. The DAF-2 receptor... DAF-2... ...kind of SCWASES-TING. Silence! And so the worm ages. Okay. So when you come along and you inhibit the activity of the DAF-2 receptor,

now you liberate DAF-16. It's free. It springs into action. And it activates about 100 genes in the DNA. These 100 genes each do a little tiny, good thing for the cell. And altogether, it makes the cell live twice as long. So let me just back up here. So there's the bad gene, the gene that says, all right, everybody died.

But the way that it tells everybody dies, it goes particularly over to this little guy over the corner who's the good guy, who's repairing and protecting and fighting disease. And it says, it conks it on the head, like some kind of three stooges thing, and says, you shut up. Exactly. So if that good guy... Actually, I'm a girl. Can stay vibrant, then we are in the ballgame for a little while longer. Exactly. Very good. And you can get a lifespan that may increase, say, 100% like the one I mentioned, even longer, even threefold.

A reefal? How'd you do that? Well, we found that signals from the reproductive system affect aging, it turns out. Kenyon and her team found that if you steal away some of the worm's baby-making powers, that alone makes them live longer. If you do that. And if you crippled the grim reaper gene, and if you strengthen the fountain of youth gene? The best possible change we knew how to make. Well, now we're talking.

We get incredibly healthy animals that live to be six times. Islam on average, which would be like 500 years for a human, and they're so healthy. It's incredible. Five hundred. So that would be like Ben Franklin still being around playing golf? Yeah, it would be. It just blows your mind to think about it. Which, by the way, that doesn't mean that it will ever be possible in humans.

Why do we turn to, why are we listening to this program? No, she kind of has to say that because she's a scientist. She doesn't know yet whether it affects us. On the other hand, she has started a company. Yes, elixir. And the company is making a pill, and it's a pill for people, interestingly. Have you any notion of how much you could slow down the process? Well, we don't know.

You know, we're just hoping that we can slow it down at all. But just imagine. Used to be people would talk about that, but it's the world of fairy tales and fantasy. And now it sort of reopens the quest for the fountain of youth in a new molecular way. Wait a second, though. What happens if she, dare I say it, succeeds with this little pill of hers? Do we necessarily want a lot of 500-year-old golfers hanging around, not getting out of the way? Well, we're already there in some places in the world.

In Germany and in Japan, the population of older people has grown to the point where you, if you're a middle-aged or younger person, you'd feel the oppression of having so many people to support. Can we talk about Japan for a second? Japan might be a canary in the coal mine, as it were, sort of a glimpse of where we're all headed. Jocelyn Ford, a reporter, has been looking at aging society. in Asia and recently took a trip back to Japan where she used to live to see how they're dealing with things. When I arrived in Japan, it was immediately obvious that there was something different here. I went into the closest little town to the airport, and there was a street festival going on. I thought great.

Went down the street and what really surprised me is I think of street fairs and kids playing and, you know, let's go out with a family. But everyone's sitting around listening to the music was, I mean, there were, a lot of gray heads. I met a guy who was like 90 years old and he was on a bicycle. And when he cycled off, I felt it's a different society. Bottom line is this. In Japan, aging is very fast, the fastest ever in the entire world. This guy banging the chalkboard, that's Hiroogawa.

Hirooga. I'm a demographer at the New Horn University Population Research Institute. Where is that, by the way? Is that in Tokyo? In Tokyo, yeah. And he said that the reason that Japan looks so old all of a sudden is because, in part, people are living longer, but that's not the big reason.

The big reason is that the birth rate is falling. Look, I mean, Japanese population is shrinking. They're not having as many kids? That's exactly it. And this is something that's happening all over the developed world. People are having smaller families. And as a result, there are fewer young people, more older people. Right now, in fact, the proportion of the elderly, I mean, 65 and old,

is more than 21% which is the highest entire world. 21% elderly. Can you imagine what that looks like? No. Just think Florida. What do you think of when you think of Florida? Florida. I think of beaches and I...

Well, that's where a lot of old folks go to retire. So I think it's of a lot of, you know, 70 and 80-year-olds. Florida is the oldest state in the United States, but compared to Japan, it's young. It's only 17% over 65 and Japan is 21%. Whoa. So imagine that all of Japan looks like Florida, just older. And Ogao expects that percentage to double in 40 years.

Right now, I mean, we cannot really picture the future scenario, but it's going to change. Well, I got some insight into that change back at the street fair. I went to get some tea and rice crackers. And in that shop, there was a 103-year-old granny. I tried to talk to her. She couldn't really communicate. She didn't really know what was going on. Her daughter, who's in her 60s, is the main caretaker.

In her 60s, wow. In her 60s, and she has to, the granny can no longer get out of her wheelchair by herself. She can't take a bath. She's completely dependent on her daughter like a baby. But she's a lot heavier than a baby, and her daughter had really strained her back, hurt herself. I mean, the elder looking after the age it, basically. And that's probably the biggest, the biggest problem. The problem is that the caregivers, a primary age of the caregivers is about

40s and 50s. So we are sort of short on caregivers. That never occurred to me that from society's perspective, the reason kids are good, are useful is so that they take care of the old people. Yeah, a government spokesman I spoke with. Thank you so much for making this help. Mr. Taniguchi. He was quite concerned about that. There's going to be a shortage of labor as society ages, and someone has got to fill the void. In countries like the United States, we might import foreign labor. Sure.

Bringing immigrants, care for the elderly, you know. But in Japan... It'll happen only reluctantly. It's not so simple. Because this society is still debating whether it's going to be a good thing or not to increase the number. immigrants. We have decided to open our labor market to some extent. Nishimura Yasutoshi. He's another government spokesman. First, we'll start. He said the government has decided they can allow

maybe more than 100 Filipino caregivers to come into the country. Just 100? Just 100. I know what you're thinking. Is it basically because Japan is xenophobic? Well, let's put it this way. Japanese people tend to have this island concept. Having more international workers in our neighborhood might dilute that kind of tradition. I think that's what the Japanese people might be worried about.

What's wrong with that? Things change. I think basically communication. Particularly when you're sick, I mean, when you're bedridden, if the nurses are foreigners, you have to communicate, and it's very difficult. You know, some people might think that's xenophobic, that's xenophobic that people don't want to deal with foreigners, but that's not really what it's about. People don't want to be a burden to anybody.

They don't want to depend on anybody. I don't want to have same burden, if you say. This is Mr. Suga. He's a demographic researcher. You just don't want to be a burden. No. This feeling that you shouldn't be a burden, it runs very deep, physically, psychologically. Both of them.

I just prefer I will. be helped not by any other people. Why is that? Just feeling. It might cause problems with them with other people. So you'd be more comfortable knowing that you're not putting anyone else, causing them trouble. Yep, yep, yep. So if I would need some help from other people, I might want to kill myself.

That's how extreme it gets. That's how extreme it gets. This is a young man who's 30. He said, I would rather commit suicide than be taken care of by somebody who doesn't want to take care of me, who I'd be a burden on. You know, there is a culture like 200 years ago in Japan. If old woman's alive until like 6, 70 years old, then family take these old mothers to a mountain and stay. there, make the mother stay there. There was a very long tradition in Japan of, they call it Oba Ste. Obaste. Oba's stay. No, oba means grandma and stay means to throw away. You're serious. I mean, they have whole movies about this in Japan.

There's one called The Ballad of Narayama. It's set in a very poor rural village about 100 years ago. It tells the story of a son, taking his old mother up the mountain. On the way up, they pass by another son, literally throwing his father off of a cliff. It makes a family happier. So grandma stays in the mountain and starves to death. Yep. Yep. The family is happier because there's less of a burden. Right. It was understood among all the generations. This is the way the problem was solved. Not anymore, obviously.

Right, right. Japan is really quite socialist these days. They look after everyone's society. But that idea is still out there. So what do you do today? You don't want your kids to take care of you. You don't want foreigners to take care of you. Who's left? Well, one solution is instead of having people do these jobs, have machines.

Machines? Robots. Robots? You joking? It's not actually a joke. Panasonic and others are manufacturing robots as caregivers. When you think about it, it sort of makes sense. Why don't we automate the heavy duty work?

Welcome to Mirai. I visited a bunch of labs and met with some scientists. And this robot is connected to here. Can I ask what that is? They've got robots that will... It looks like a dentist chair. Tell your wheelchair where to go. I wonder how fast this is going.

There's a special pair of trousers that you can put on, and if your legs are weak and you can't walk well, It will help you walk. There's a washing machine robot. It looks like it's got a fancy handle. It's actually for washing people. Are any of these in actual use? Yes, they are.

People do not want to have to ask somebody to clean their diapers, to wash their bum. Right. I think for anybody in any society, that is a difficult thing to have to ask somebody. Robots are more. I mean, you don't have to talk. You just press the button. Now this is where I start to get weirded out. I went to a nursing home about an hour and a half.

outside of Tokyo. Lots of people mostly sitting around. There's a television about three people are watching the TV. One's looking out the window. I walked in and there were a lot of old people just sitting around, each keeping mostly to themselves, sitting very quietly, not talking. It was sort of sad.

In Steps, Paro the Seal. Paro is one of the world's first therapy robots. Get it? No. What does that mean? What they've done is they've made this sort of like a large stuffed animal, white furry, long eyelashes and it flutters them at you. And it squeals.

When Paro came out, one of the grannies just lit up. Got so excited. She peered into the seal's eyes and she tried to talk to it. She said that I'm happy to come to Paro. It's the same feeling when her family come here. I was taken back. I mean, it's not much more than a moving stuffed animal. How could you look at it and see company, see something alive,

see something comforting? I feel a little bit warm. Is Perra warm? Yes. Paro has kind of temperature control. I spoke to the developer, Mr. Shibata. So you're warm-blooded, huh? He said, yeah, they wanted a creature that would give them positive feedback,

but also sort of needed them. Being struck is good for Paro. So Paro tried to be stroked by the owner. Like you're doing right now? Yeah. Did you program to want to be held? Yeah. He also programmed them to respond to different names.

Yeah. So, for example, I call him as Paro. If you give a new name, like John or something. Or like Choko Chan. And call the new name again and again. Chugajan. Chugajan. Paru gradually run the new name and start to respond.

So it's learning? Put you down carefully because we don't want to hurt you. Oh, you want to be held again, huh? They learn from their environment. Now, these are really rudimentary, you know, beginning baby robots. But it worked, Chad. It worked. I started to think.

Yeah. Wow to make. They adored it. They were loving it. And it was loving them in their minds. I started to think maybe this is a solution. People might actually be able to engineer compassion, engineer companionship.

But then I started asking a lot of people around me, took an informal straw pole, would you feel comfortable with a robot taking care of you? And most people said, no, not really. Like this woman, Keiko Sugi, she actually came up with a brilliant idea, which seems like a no-brainer.

She has a nursing home, which is together with a preschool. So we'd like to take a tour. You walk into the room and you are bombarded by these little bodies. Screaming and flying around. The vitality is just over the top. And it's infectious. And if you're an old person in that environment, you have no time whatsoever to dwell on the idea that you are dying.

The kids are, they demand your attention, they need you. They're needed again. But the first thing that you told us, the very beginning, was that there are more old folks, less kids. Well, what happens when these kids were listening to right now when they dwindle? There's just a bunch of old people around and there's maybe one kid left and they all go to visit that one kid. I mean, that can't work. Do you expect me to have an answer? I don't know.

Maybe we should import kids. I don't know. No, I mean, you're joking, obviously. But I guess what I'm asking is, like, are we left at the end to think that a society cannot support? all of its members getting old that somehow the old have to step out of the way. Dad, I think your thinking is basically old-fashioned. There will be more old people and fewer young people.

That's a fact. You're not going to turn the clock back on this. Societies do change. People do come up with new ideas. And right now, hey, they're stabbing in the dark after them. But one day, they'll come up with a solution. So learn to deal with it. Damn, you just bitch-slapped me.

Well, what do you expect? He pulled me all the way across the Pacific Ocean, across a whole continent. Dude, we're going to go to a break now because I've got to sort of pick up my ego here. Radio Lab will continue in a moment. This is Casey calling from Fort Myers Beach, Florida. Radio Lab is supported in part by the National Science Foundation and by the Alfred P. Sloan Foundation, enhancing public understanding of science and technology in the modern world. More information about Sloan at www.sloan.org.

This is Radio Lab. I'm Chad I'm Robynod. And I'm Robert Crulwich. And in this hour we've been talking about aging mostly, but now we're going to turn our attention to the end of that aging process. You're talking about dying? Yes. Maybe we've avoided that topic because that's generally how people deal with death, which is to avoid it. To deny it, yeah. This next piece is about actually a different way of dealing with death.

I should say before we begin it, that it does contain some graphic descriptions of the normal bodily process of aging, but if you have someone in the room who is squeamish or you don't think you should hear these things and it's nothing terrible. It's actually quite nasty. Yeah, it's nasty. It's nasty. Then maybe this is the time to shoe them out of the room.

This piece was produced by Lou O'Kalski. It's about one family, three generations. Introduce myself. This is Jeremiah, the youngest. I'm Jeremiah Zagar. He's a filmmaker. Son of Isaiah Zegar. His dad, Isaiah is a muralist.

And his grandfather, I'm the grandson of Asher Zagar. Asher Zagar is a health night. This is a video of him that Jeremiah shot of Asher doing his daily exercise routine. He's in his 90s. He's jumping on a trampoline and counting each jump. How old are you now? Me?

I'm 90. 90. You're a healthy man for 90. Yes, and I'll be. Still healthy when I'm 91, 92. The great-great-grandfather that I named after lived to 102. So you're going to live to 102? I don't know, but maybe.

At the age of 93, Asher began to decline quickly. How do you deal with a man dying in your house? How do you deal with that? Well, you know, my father starts taking photos of him. One of my modes of understanding was either, drawing or photographing. He was always taking pictures of my grandfather. Just see it.

Thousands of slides. Thousands. That's how it went for a while. Isaiah, the dad, would take care of his dad and take some photos. While grandson Jeremiah basically looked the other way. Well, I never really knew my grandfather. But then Isaiah got an idea. I thought to myself, challenge this young boy to this duel.

Who can take the most objective? photographs of a dying man. It wasn't like we threw down and like I pulled my camera out of my holster and he pulled his camera out of his holster. You know, it wasn't like that. He was involved in my grandfather's death and I wasn't. And so he said, this is how I get involved. It's my senior year in high school.

And I was a busboy in this restaurant down the street and I loved it. And I would bus tables till two or three in the morning and then I would get drunk with the people after work. And then I would come back and I would take care of my girlfriend. grandpa. So I would lift him up and change his sheets because otherwise his bed sore would burn more when he had this horrible bed sore. You can see it in the photographs. And he would hit me while I lifted him up. And then I would photograph him because I would want to sit with him because you want to calm him down. And the way you sit with him, I mean, my father was right. You have the camera. I mean,

that's how you cope. Otherwise, you're sitting with him and he's just looking at you. During the contest, dad and son shared duties of taking care of Grandpa, and at night, they'd sit at the kitchen table and compare photos. As soon as I took the first pictures, you knew mine were better than my father's, because my fathers were from far away, and there were snapshots, and mine were, like, specific. Like, I was fascinated with him dying. I wanted to know what it looked like.

And this went on for about a month, during which time even Jeremiah's friends... All of his friends got involved. The wee hours of the night, I would wake up and I would see that they're surrounding my father or four or five young people. Sure, they were drinking beer and they were joking around, but they were there. They were there while he was there. What I remember most was you and your friends changing his sheets and lifting him and moving them around. Yeah, Gabrielle did it with you.

Who else did it with you? John. Lincoln. They all became initiated into the most problematic event in our lives. It was an amazingly rare scene to see these teenagers attending to death. Well, this is a book of photographs of my father, your grandfather's last week of life in this very room. So the contest was a month long. Smart guy I am, huh? You're good. You know how to make a contest?

I kept it going for one month. Good job. Isaac, can you describe this one for me? Well, the feet look like they were out in the desert, that they've been baked and cracked and they're dry, dried out. I mean, look at them. They look like... I mean, look at the nail. The nail is wild. wild but I mean everything it's like what I have these same legs stop touching photos

I can almost feel him like feeling them I'll feel you instead no that's the bed sore that's what happens oh it's awful awful oh awful awful man who prided himself on his health Look what happened. How does one describe that? It looks like rotting me. I mean, they're just open wounds, and you move them around, move them around, but still, it was impossible.

It's crazy to look at the colors, too. Pink and then white, and then green and then brown, where it's really... Well, the white is the muscle, isn't it? I took these photos in color because in black and white, you'd never get it. You know, you'd never get how painful this must have been. His anus is all red.

I mean like really red And you can see That parts of it have broken And there's just blood gushing out And it's dried I mean the blood is dried I think this is the last photo

This one's tough You can see like the cognition is gone The mouth is a gape He's buried in his pillow He knew it was over It was just a matter of time now That's it That's the closest I got to him dying

He wanted to live forever The fix was in for from the beginning. The fix was in I was supposed to win? Sure. Sure. How could it be any other way? I don't know.

I could have taken a lot. I could have given it up? You wanted me to win? It was a subterfuge to get you to be with your grandfather as much as possible. I thought it was a fair fight. It wasn't. Can there ever be?

Can there ever be? He knew all long that he couldn't take a good picture. When a person is dying, it's very important that they're surrounded. They're surrounded by the light of life and you don't go into the place of oblivion alone. You want me to be there? I don't know.

At this point, I don't know. I'm not at that place yet. Well, what does that mean with the camera? I mean, just be with me. Yeah. Be with me. Be with me. Be close to me. Be soft with me.

Yeah, I guess that's what it's about, really. It's all for me. Thanks to Lou Elkowski for that story. And to Isaiah and Jeremiah Zegar. And, well, we've come to the end of our hour. I guess we should wrap. Mm-hmm. We should mention the website.

Yes, radiolab.org is the address. And also, if you want to sign up for our podcast... How do you do that? Well, you go to radio lab.org or to iTunes directly. And if you want to send us an email, Robert. If you want to send us an email, you should really write us to our email address. Which you can never remember. Radio Lab at WNYC.org.

Is our email address. I'm Jed Abumran. And I'm Robert Crilwich. We'll see you later. Abusrad. Ellen Horley. This Isaiah Zegarar. Production support by Sarah Pellegrino, Mark Phillips, Scott Goldberg,

Sam Lavender, Aver Mitra, Ryan Schemel, and Jacob Weinberg. Special thanks to Jocelyn Ford, Sam. Dingman, Leonard Lopate, Josh Kane. This is Jeremiah Vega. I want to thank you for listening. Radio Lab is supported by a grant from the Alfred P. Sloan Foundation. Radio Lab is produced by WNYC, New York Public Radio, and distributed by NPR National Public Radio.