[RADIOLAB INTRO]

JAD ABUMRAD: I'm Jad Abumrad.

ROBERT KRULWICH: And I'm Robert Krulwich.

JAD: And this is Radiolab.

ROBERT: You ever wondered why it is that all living things die?

JAD: I do wonder about that, actually. It keeps me up at night.

ROBERT: Which always leads me to the next question: do we have to? Do I have to?

JAD: The topic of our show, as a matter of fact. And a natural place to begin to look for an answer is in a garage.

JAD: Here we are in your garage.

LEONARD HAYFLICK: Here we are in my garage.

JAD: 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 ...

JAD: Wow, so describe what we're looking at here.

LEONARD HAYFLICK: Well, what we're looking at is a barrel-shaped device made out of metal that is actually ...

JAD: It's a metal canister that is shaped kind of like a thermos, except bigger.

LEONARD HAYFLICK: So I'm opening the lid ...

JAD: He twists off the top and—whoosh!—out comes all of this smoke.

JAD: Dry ice from Halloween is what it looks like.

LEONARD HAYFLICK: Well, this liquid nitrogen is used in a lot of movies.

JAD: 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 ...

LEONARD HAYFLICK: Those are the—those are what we call ...

ROBERT: What?

JAD: Some test tubes.

ROBERT: Oh.

LEONARD HAYFLICK: Tubes in which these samples are kept.

JAD: 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.

JAD: And you keep it in your garage?

LEONARD HAYFLICK: Yes.

JAD: Why? I mean I think it's pretty cool, but why ...

LEONARD HAYFLICK: Because nobody will think of looking here.

JAD: Oh, okay. Well I won't—I certainly won't divulge your address or anything, but ...

LEONARD HAYFLICK: No, please don't tell anybody.

JAD: No, of course I wouldn't, but ...

JAD: It's in California is all I'll say.

LEONARD HAYFLICK: Well, where else would you want me to put it? In my bedroom?

JAD: No, I don't know. I mean it's—I imagine something like this, you would find it in the middle of ...

JAD: It started for Leonard Hayflick about 50 years ago. I got the backstory actually not in California, in Philly.

JAD: Soundcheck. Do you wanna tell me where we are?

LEONARD HAYFLICK: 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.

JAD: 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 your wrist—well, you know, I guess you could, but ...

LEONARD HAYFLICK: I wouldn't say it's impossible, but it's certainly highly impractical.

JAD: What you can do instead, and Hayflick was among the first to perfect this, is—well, he explained it to me.

LEONARD HAYFLICK: If I take a tiny biopsy from any part of your anatomy that you're willing to surrender to me ...

JAD: Like say, a fleck of my—like, my wrist. A fleck of my wrist.

LEONARD HAYFLICK: Your wrist, your—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 trypsin. 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.

JAD: Right.

LEONARD HAYFLICK: 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.

JAD: I mean, you know, that's if you had a big enough petri dish. In any case, this process, it's called "cell culturing." It is the simplest thing in the world these days. I mean, modern biologists can do it with their eyes closed, but back in Hayflick's day in the '50s, it was very fuzzy.

ROBERT: Hmm.

JAD: 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 into 16, whatever, they ...

ROBERT: Yes?

JAD: They—it was like they had the touch.

LEONARD HAYFLICK: They had what was called a green thumb.

JAD: There was a mystique about them. Because, you know, don't forget, this was the early days. Biology ...

LEONARD HAYFLICK: Cell biology at that time ...

JAD: ... was still kind of a black art.

LEONARD HAYFLICK: Well, I'm interested that they used the term "black art," because 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 Carrel. 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 the rationale for that because I can't explain it.

JAD: That's so gothic, I love it!

LEONARD HAYFLICK: 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.

JAD: It must have seemed like witchcraft, almost.

LEONARD HAYFLICK: It didn't seem like, they believed it was witchcraft. Especially because Alexis Carrel claimed to have kept a chick heart alive for 46 years.

JAD: A chick heart.

LEONARD HAYFLICK: Yes.

JAD: Like the heart of a baby chicken?

LEONARD HAYFLICK: It was a fragment of tissue from the chick heart.

JAD: So for 46 years the cells divided and divided every couple days?

LEONARD HAYFLICK: Right. That's what was alleged.

JAD: Now 46 years is a long time, right?

ROBERT: Yeah, I'll say.

JAD: And so scientists thought that if they've gone this long they'll probably go forever.

LEONARD HAYFLICK: Forever.

JAD: Because of Carell and a couple other scientists, it was thought that cells are immortal.

LEONARD HAYFLICK: Under the proper conditions, they'll grow indefinitely.

JAD: And Carell's little chicken heart seemed to be proof of this. It just kept spewing new cells, which he'd keep dividing into new bottles.

LEONARD HAYFLICK: As the New York Post said, "If all the cells produced by Doctor Carrel from his cultured chicken heart were kept together, they would produce a rooster that could cross the Atlantic Ocean in a single stride."

JAD: [laughs] I wish I'd come up with that myself. Now was that a quote that was made lovingly or admiringly, or was it a sort of sneering quote?

LEONARD HAYFLICK: It was made to sell the New York Post.

JAD: But people bought it, I guess is what I'm asking.

LEONARD HAYFLICK: You're darn right they bought it. Until it was torpedoed by me.

JAD: Right. Well, that's the story that I want to get to next.

JAD: 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.

LEONARD HAYFLICK: I knew at the time that if you cultured normal human tissue from adults, you might grow simultaneously unwanted viruses.

JAD: Because in adults, the viruses would sometimes sneak into the cells and hide there.

LEONARD HAYFLICK: And I didn't want, of course, my cultures to be contaminated with these viruses, so I zeroed in on human fetal tissue.

JAD: Human fetal tissue. As in from abortions.

JAD: Now sorry to ask an ignorant question but abortion at that time was—was it anything like the crazy political thornbush that it is now?

LEONARD HAYFLICK: No. Far more rational.

JAD: It was actually quite easy, he says. He just picked up the phone ...

LEONARD HAYFLICK: 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.

JAD: He never knew when the shipments would arrive.

LEONARD HAYFLICK: I would receive maybe one fetus one week, and then two weeks later another one.

JAD: 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 drop the cells into the flask, watch them divide, do the whole deal. And then every couple weeks he would come check on them. And that's when it started.

LEONARD HAYFLICK: I began to realize that some of the cultures are unhappy, they stopped dividing.

JAD: At first it was just one. One batch.

JAD: What were you thinking at this point?

LEONARD HAYFLICK: I didn't know what to think.

JAD: Because it's just an observation and it was just one batch—batch A let's call it. Yeah, all right. No biggie. We'll see how it goes.

LEONARD HAYFLICK: 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.

JAD: Now three batches of cells had gone kaput!

LEONARD HAYFLICK: I said to myself, "Well, that's peculiar."

JAD: Peculiar because here he'd done the same with these cells as he'd done with all the others. He'd put them in the same glasses, same solutions ...

LEONARD HAYFLICK: Same conditions.

JAD: Didn't add up.

LEONARD HAYFLICK: Now I had to find out what the cause is. So I go back and look at my records.

JAD: And that is when it smacks him in the face.

ROBERT: What?

JAD: The thing that all three batches of cells had in common, 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 ...

LEONARD HAYFLICK: I received it from the hospital ...

JAD: ... roughly ...

LEONARD HAYFLICK: ... nine months ago.

JAD: And at nine months or thereabouts, they just kind of hit a wall and they stopped dividing.

LEONARD HAYFLICK: But the ones received one month, two months, three months, four months, five months, six months ago ...

JAD: Those cells were doing just fine.

LEONARD HAYFLICK: Perfect, beautiful.

JAD: And he kept seeing this. Simultaneously, two thoughts enter his mind. Thought number one: this can't be an accident.

LEONARD HAYFLICK: If it was an accident it should be random.

JAD: Uh-uh. Thought number two: wait a second, this has to be an accident.

LEONARD HAYFLICK: Because I had been taught by experts ...

JAD: That cells are immortal.

LEONARD HAYFLICK: ... they will grow forever.

JAD: All right. Fast forward a few months, those two conflicting thoughts are still fighting it out in Hayflick's mind, and along comes the annual biology conference.

LEONARD HAYFLICK: The biggest scientific meeting in the world. That time, the meeting was held in Atlantic City.

JAD: Hayflick and a few friends decide to hop in a car and crash the meeting, because the featured speaker was a guy Hayflick really admired, a guy by the name of Ted Puck.

LEONARD HAYFLICK: Because I want to hear what he has to say and I'm gonna—if I can get enough guts, I'm gonna ask him a question.

JAD: Hmm.

LEONARD HAYFLICK: 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 and lots of people, and I'm somewhere in the middle, listening to his talk.

[ARCHIVE CLIP, Ted Puck: You see the methods previously developed whereby single cells ...]

LEONARD HAYFLICK: And at the end, as is customary, he asked for questions.

[ARCHIVE CLIP, Ted Puck: Are there any questions?]

LEONARD HAYFLICK: I timidly raised my hand.

[ARCHIVE CLIP, Ted Puck: Oh yes, the young fellow in the center. Yeah, you.]

LEONARD HAYFLICK: And I ask him the following question: Dr. Puck ...

[ARCHIVE CLIP, Leonard Hayflick: Have you ever found that the cells that you culture stop dividing?]

JAD: Did you want to give him a kind of a gotcha, or what were you thinking?

LEONARD HAYFLICK: 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 do it right.

JAD: I see.

LEONARD HAYFLICK: I'm still worried.

JAD: Got it.

LEONARD HAYFLICK: And so he says—he looks at me, you know, like I'm an idiot. Well, of course ...

[ARCHIVE CLIP, Ted Puck: Well of course the cells stop dividing occasionally. Of course I lose my cells occasionally. But I simply go back to the freezer and reconstitute them.]

JAD: Meaning that when the cells stop 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."

ROBERT: Well, that's not right. Because if they stopped dividing they might have just died.

JAD: It's not that he was cheating, it's that he thought he had screwed up.

ROBERT: Oh.

LEONARD HAYFLICK: Then I knew it was a gotcha.

JAD: 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 it for what it was.

JAD: 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 [bleep] up."

LEONARD HAYFLICK: Absolutely.

JAD: That seems like a crazy kind of mass delusion.

LEONARD HAYFLICK: It's called dogma. Is there—you know the definition of the word dogma?

JAD: [laughs] Yeah, I've heard that word before.

LEONARD HAYFLICK: That's it. The concept of mortality was absent from people's minds.

ROBERT: Well, wait. If they didn't understand the idea of mortality, then how did the scientists explain getting older and moving towards death?

JAD: Pre-torpedoing?

ROBERT: Yeah.

JAD: Radiation.

ROBERT: What?

JAD: Radiation.

ROBERT: What—what do you mean? [laughs]

JAD: No, seriously. I mean, it was this idea that, like, stuff was happening outside the cell, that the radiation is bombarding the cell, like gamma rays and alpha rays and these kind of things, and that that somehow ages the cell.

ROBERT: So the trigger is outside the being not inside the cell.

JAD: Right.

LEONARD HAYFLICK: 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.

JAD: Hayflick argued that somewhere in the cell there's a counter. There's gotta be, because something in the cell is keeping track. Because after about nine months of happy dividing in a petri dish, when a cell gets to 50 divisions, sometimes it's a few ticks more, a few ticks less, but 50 is the average. And when it reaches 50, a little counter inside the cell says ...

["Stop!"]

JAD: 50 is the magic number.

JAD: Where did this number 50 come from?

LEONARD HAYFLICK: You'll have to ask God that question.

JAD: 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 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.

LEONARD HAYFLICK: The cells I have in my freezer have been frozen for 44 years.

JAD: Does that make them the longest ...

LEONARD HAYFLICK: These cells are the longest frozen, normal human cells in the world.

JAD: The fetal cells he's talking about, incidentally, are the ones that he used to discover the Hayflick limit. He calls it WI-38.

JAD: What do we know about the mother of the fetus that created WI-38?

LEONARD HAYFLICK: 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.

JAD: Here's the kicker: after the Hayflick limit experiments, these cells, this particular strain was used to incubate and produce vaccines, all different kinds.

LEONARD HAYFLICK: Polio, German measles, measles, mumps, rabies ...

JAD: And anybody born in the last 50 years who's had any of these vaccines has had these cells in their body.

LEONARD HAYFLICK: The numbers of people who have benefited from these vaccines now exceed one billion people.

JAD: That's billion with a B.

LEONARD HAYFLICK: That's a billion with a B.

JAD: Wow.

JAD: One aborted child creates a fleet of cells that vaccinate a billion people. Think about that for a second.

JAD: And is it true that you have a cell line from—is it your daughter?

LEONARD HAYFLICK: Yes. I also have cells in there from the amnion of my daughter, Susan Hayflick.

JAD: And do you keep them for purely scientific reasons? Or is it sort of like stamp collecting? You have them as ...

LEONARD HAYFLICK: Well, it would be—she's a scientist now herself, and so I'll probably give the ampules to her so she can do with them what she wishes.

JAD: But you keep them because it's your daughter mostly.

LEONARD HAYFLICK: Yes, mostly. Yeah, sure.

JAD: Aww, that's really sweet!

LEONARD HAYFLICK: [laughs]

JAD: Here's the interesting thing, scientifically: if you were to warm these cells up, give them some food, they'd start to divide again. And not only that, they'd pick up right where they left off. And even if you froze them again—let's say the 16th doubling—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.

LEONARD HAYFLICK: What does that tell you? Tells you that cells remember. They have a memory.

JAD: Somehow the cell always remembers where it is in the count to 50.

ROBERT: Cells can't count. How do they do that?

JAD: Well, that's—that was the next big question.

LEONARD HAYFLICK: So we set about to do a number of experiments.

JAD: However, the next big breakthrough came in 1971 and not by Hayflick. While he was doing his experiments in Philly, halfway across the world at the very same moment ...

LEONARD HAYFLICK: A Russian named Alexey Olovnikov ...

JAD: ... was attending a lecture ...

LEONARD HAYFLICK: ... heard a lecture ...

JAD: ... about Hayflick's research. And he left the lecture puzzled by this question that you asked: how do the cells remember?

LEONARD HAYFLICK: And when he—have you ever been to Moscow?

JAD: Mm-mm.

LEONARD HAYFLICK: 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.

JAD: First thing he thought was: those tracks look a lot like DNA.

LEONARD HAYFLICK: If you take railroad tracks and you twist them ...

JAD: You twist them, yeah.

LEONARD HAYFLICK: You've got DNA.

JAD: Okay, say you had some DNA, and that DNA's job is to count to 50 and then yell ...

["Stop!"]

JAD: 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 ...

LEONARD HAYFLICK: A long sequence of nonsense.

JAD: ... 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 snip 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 ...

JAD: Shouldn't we theoretically be able to figure out how to tinker with when the switch gets switched?

LEONARD HAYFLICK: In theory, I suppose you could. Yeah, sure.

JAD: And wouldn't that allow us to have a longer amount of cell divisions?

LEONARD HAYFLICK: Well, that certainly doesn't violate any knowledge about this system, of course.

JAD: And wouldn't that theoretically give us something, whether it be extended life or something?

LEONARD HAYFLICK: Yes. Certainly.

JAD: Hayflick 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 ...

LEONARD HAYFLICK: Telomerase.

JAD: ... throw it into the mix, and every time that cell gets copied and loses pieces of track, the telomerase enzyme comes along ...

LEONARD HAYFLICK: And it adds them back on. And maintains the length constant.

JAD: That way the track is always long, the stop switch never gets switched, and the cell can keep going and going and going.

LEONARD HAYFLICK: That's how they become immortal. So you're not gonna tell me, "Well, let's inoculate everybody with telomerase."

JAD: Yeah. And?

LEONARD HAYFLICK: [laughs] Well, if you volunteer we'll have a shot at it. Are you ready?

JAD: There—there must be—if I were to go out and shout from your balcony right here ...

LEONARD HAYFLICK: You have to remember this.

JAD: ... I'm sure I'd get a hundred people who would want to try.

LEONARD HAYFLICK: Really? Not after I tell you what you still don't know.

JAD: What's that?

LEONARD HAYFLICK: 95 percent 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.

JAD: So the tradeoff for cellular immortality, at least in this case, is cancer. But here's the weird thing: if you look around, you'll see that our Hayflick limit of 50 is not the only one.

LEONARD HAYFLICK: 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.

JAD: So their Hayflick number is 125 and ours is 50?

LEONARD HAYFLICK: Apparently, yes.

JAD: Does that correlate to the Galapagos turtle living twice as long?

LEONARD HAYFLICK: Well, it seems to, but that comparison may be anecdotal and not universal.

JAD: 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!

LEONARD HAYFLICK: There are a whole class of animals that don't age.

JAD: Well, like what?

LEONARD HAYFLICK: The American lobster.

JAD: The lobster doesn't age?

LEONARD HAYFLICK: It either does not age, or the rate is so slow we can't measure it.

JAD: I don't even know how to imagine that. What does that mean, is that it doesn't ...?

LEONARD HAYFLICK: Well, what it means is that the animal gets bigger and bigger.

JAD: Just grows?

LEONARD HAYFLICK: Yes. There are lobsters that have been found—recently I read about one that's over 50 pounds.

ROBERT: 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.

JAD: Hey, New Jersey!

ROBERT: Yep.

JAD: How old is a—how old is a 50-pound lobster? Who knows?

ROBERT: The one indication it was wearing a Grover Cleveland for President button. So it was very old.

JAD: [laughs] I'm Jad Abumrad.

ROBERT: I'm Robert Krulwich.

JAD: This is Radiolab.

ROBERT: We'll be right back.

 

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