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				A Passion for DNA James Watson helped discover the Double Helix, and fathered modern genetics.
		Select text to jump ahead in the clip: ALDA: When we decided to make a show about DNA-- the stuff genes are made of-- we naturally wanted to start with some of the finest DNA we could find. So we came here to the DNA Learning Center on Long Island. MAN: The first thing we're going to do we're going to swoosh our cheek pockets really good. Now, I have to tell you you're going to get the DNA of the tuna I had for lunch. So my DNA's right there in that little cup, huh? Take a peek under the microscope; you'll see thousands of cheek cells that just sort of slough off. I see. That blue dot in the center is the nucleus? The nucleus. This is my nucleus. ALDA: It's the nucleus that houses the DNA so we have to break it up and shake it up to release my genes. Okay, I got it. ALDA: Unlike me, the high schoolers whose class we've dropped in on aren't in the least amazed that you can get your hands on your own genes and chop them up multiply them, even read what they have to say. They've grown up during the years when scientists have pretty much deciphered the entire human genome. . . I'm a nervous wreck. ALDA: The three-billion-letter instruction manual for making a person. You want more? Science is hard, I'll tell you. ALDA: Our show is about the people who are picking through the DNA-- not just of humans but a strange menagerie of other creatures-- to find out how this unimpressive looking gook has within it some of life's most precious secrets. What'll you give me for this? (chuckling) ALDA: One of the first people to imagine that DNA was worth anything was Jim Watson who, with Francis Crick 50 years ago, discovered the double-helix structure of DNA-- a structure now echoed in this staircase outside Watson's office at Cold Spring Harbor Laboratory just down the street from the DNA Learning Center on the north shore of Long Island. (conversing quietly) Jim Watson first came here in the late 1940s as a 20-year-old graduate student obsessed with finding out what genes are made of and how they work. WATSON: I thought it was the only problem worth solving. Of course, that wasn't true but it was the only one Ithought worth solving. And, uh, luckily... except for Francis Crick I don't think there was anyone who was, you know as high about DNA as we were. ALDA: Hmm... ALDA: Watson and Crick discovered their mutual passion for DNA when Jim went to Cambridge, England, in 1952. But most biologists didn't share their enthusiasm and dismissed the pair as arrogant and irrelevant. Watson later wrote about this period inThe Double Helix his famously candid account of their discovery. WATSON: No one predicted, you know... thought we were ever going to succeed. And England is too polite to have too much ridicule but, you know, no one was betting on us, and, uh... you know, our obsession about DNA... You know... 'Prove it.' You know, 'And why are you so excited?' And so... you've got to be... nothappy that other people don't believe you, but just... I wrote inThe Double Helix-- and it still offends people-- that when you get into science you realize that most scientists are stupid. (snickering): And... because... Hey, wait a minute, now, come on... Yes. No, but yeah... I think that's a correct way of looking at it because they don't see the future. You know, it's a relative matter whether you call them stupid or not, but, you know... How can anyone with a Ph.D. be stupid? But most people with Ph.D. aren't doing anything you know, doing anything, uh... breathtaking. So... you have to be prepared not to care that most people think you're going in the wrong direction and that means you have to... Well, one, it pays to have someone else who agrees with you, so Francis and I could talk to each other and we never tried to persuade anyone else. There was no point of trying to persuade anyone else. ALDA: One Saturday morning in early 1953 Watson was fiddling with a model of a possible DNA structure based on a double helix. That Saturday, when things fell into place what piece was missing from this? What did you...? Well, we didn't have this. This was missing. We had the background but we didn't know how to fill in the center. ALDA: The center had to accommodate the four different chemical units, or bases that DNA is made from, known by their letters as A, T, G and C. Watson was trying to make matching pairs of bases but they just wouldn't fit. So you were pretty sure it was a double helix but you didn't know how these base pairs fit together, huh? Yeah, yes. And in the books the chemistry was written wrong. In what way? Well, they had an atom in the wrong... a couple atoms in the wrong place. And so someone said 'Well, the chemistry in the books is wrong.' Well, that must have thrown you for a few months. Yeah, at first I said, 'No, I don't believe you.' But then the next day I thought 'Well, we'll see what happens if you...' you know... Change it from the way it is in the book? Yeah, and then the whole thing fell out. So if we hadn't had that chemist in the room with us he wouldn't have been someone to say 'Well, it's wrong.' ALDA: But it wasn't just that the corrected As and Ts, Cs and Gs fit snugly in the center of the double helix; The structure immediately suggested the answer to the gene's central mission: carrying information and copying it from generation to generation. The information could be carried in the letters and the copying achieved by each strand of the helixes becoming the template for a new matching partner. So in one stroke, Watson and Crick had the answer not only to how genes are made, but how they work. WATSON: This was just much bigger than anyone expected and... in a way, it was so beautiful. There wasn't the usual jealousy of us. You know, people could rejoice in the answer. People just liked that discovery. They found it... they found it so beautiful that their natural jealousy faded away in the glare of its beauty. Yeah, I think it was, uh... Everyone hoped it was right, because if it was right we finally had the molecule of heredity because, while Francis and I were very... believed strongly DNA was going to be the genetic molecule most people didn't. And it wasn't until people saw the double helix that sort of the world of science accepted DNA as a genetic molecule. And that then led to the, you know, uh... a lot of people suddenly coming in and following up our work and the explosion of molecular biology. My office was up there... before I moved... ALDA: In the years that followed many of which Jim Watson spent here as director of Cold Spring Harbor Laboratory he continued to play a central role in unraveling how genes work. In the late 1980s when a group of biologists began to consider the then outrageous idea of deciphering all the genes in the human body it was to Jim Watson that they turned to lead the project. WATSON: I was in favor of it because even though it seemed premature it seemed to be the only way to understand a lot of disease; and, uh, I was then in my 50s. By that stage, when you're in your 50s you're seeing your parents die or dead and you're conscious of disease. When you're 25, hopefully you're not, you're not thinking... You're thinking in terms of life, not death or sickness. And, uh, so I saw getting the human genetic information as a big plus toward moving medicine. And, uh, that's how we helped, uh, sell it to Congress-- it was really disease.

				Gene Reader The Human Genome Project is being completed, one letter at a time.
		Select text to jump ahead in the clip: ALDA: Back at the DNA Learning Center, I'm finding out for myself why many biologists originally opposed the Human Genome Project even if it promised to revolutionize our understanding of human disease. Oh, there it is. ALDA: The techniques of handling and reading DNA were slow and cumbersome. Reading three billion letters' worth would involve thousands of people working, literally, for decades. But then came a revolution. This is the Whitehead Center for Genome Research the largest of the 16 laboratories around the world collaborating on the Human Genome Project. There are people here but they're far outnumbered by machines. ALDA: Wow, this is amazing. Look at this. ALDA: The director of the Genome Center is Eric Lander. This is some kind of robot? Yeah, over there you got... all those little spots on the plates. Those are each separate bacterial colonies. Every one of them has a little piece of human DNA that we've got to sequence. It might have 2,000 letters of human DNA. The first thing we've got to do is we've got to pick them up and grow each bacterial colony up so that we get enough DNA out of it. I presume this robot is doing this because it's doing it a lot faster than humans could. We used to do this-- not so long ago, ourselves, with toothpicks. So this is simply a highly automated toothpick somewhat more expensive, much more efficient. Every one of those is a different sentence in the human genome. And so we've got to go collect these random shreds of sentences and sequence them. That's pretty much what the entire operation here does. ALDA: The machines in this room diligently prepare 100,000 sentences a day of the three-billion-letter book that's the human genome. The next trick is to read those sentences. That's done here in another huge room crowded with bland-looking machines tended by a handful of humans. The humans' job is to feed the sentences into the machines-- 96 at a time-- in these little cartridges. To read the order of the letters-- the As, Ts, Gs and Cs-- in the sentences the machines make use of a process that sounds kind of odd. LANDER: Well, it turns out that little sentences move faster than big sentences when you put them through... Jell-O, in essence. I mean, now, what is Jell-O? Well, you have this... you have this giant scientific laboratory devoted to putting sentences through Jell-O. That's roughly right... I'm amazed I didn't come up with that. We'd like to use fancier words because it's impressive and it costs a lot of money but basically you're taking little molecular sentences and putting them through Jell-O. The point about Jell-O is it's this very complicated network. The little sentences can wiggle through better than the big sentences. And in fact, what's really cool about this is that the guys who are 50 letters long get there just a little ahead of the guys who are 51 letters who are a little ahead of the 52-letters. Then the sentences that are 75-letters are lagging behind. And there's this little detector that reads the letters as they go by. So in fact, if we find a machine... Guys, have we got a machine where we can bring up the letters as they're going by? TECHNICIAN: Yeah. Let's go take you to see the letters going by. ALDA: The letters, it turns out, have colored tags to identify them-- red for a T, green for an A, blue for a C and yellow for a G. So you can read out the DNA sequence, 'G-A-T-T-C-G' because we attached the right colors to the right letters and we just read their color. It's a beautiful trick. ALDA: For me to understand the trick took about ten minutes in front of a nearby white board. You've got some DNA sequence here. ALDA: But to save time, we'll summarize: The DNA sequencing machine is actually making copies of the DNA sentence-- but every time one of those colors is stuck on, the copying grinds to a halt. So there are lots of sentence fragments of different lengths floating around in there, each one ending in a different color. A sentence that's 33 letters long and is labeled red, for instance means there's a T at position 33. Reading all the different fragments eventually fills in the whole sequence. Number six is purple. Right, right. And the number seven is green and the number eight... that's it. Mmm... okay, thank you. That's the end sequence! That's all there is! This whole place is here to stick in these things. All right, well, let's go. Yeah, I'll run one of the machines now. That's it. You've got it. (laughing) That's freshman... It takes an hour in freshman biology but you've got it, that's it! ALDA: Well, that's a relief. But there was still one nagging question. Just who exactly is the human whose genome is being read? ALDA: If you took my blood cells and went through this whole process... do you need to get a lot of other people's blood cells to get a comprehensive picture of human... the human genome? Your DNA and my DNA are 99.9% identical. We differ at one letter in a thousand. So if what we're trying to do is find all the genes in the genome all the sentences, we can do that just fine whether it's your DNA, my DNA or anybody else on this planet. Once you've read one person's DNA you then become interested in this one letter in a thousand variation. And that matters. I mean, between you and me I said we're 99.95 identical but we also have 30... sorry, three million differences... And one of us might have something that's off that could cause disease, is that right? Oh, one of those letters could be breast cancer one of those letters could cause early onset Alzheimer's disease. You want to know the differences. But it's as if you had many different editions of the same book, and they differed by, you know a comma here, or the British spelling of some word here instead of the American spelling. So when you say 'Well, what do we mean to read the book?' Anybody's copy of the book will be fine if you want to get the story line down. If of course we really care about the punctuation-- and at the end of the day in medicine we really do care about the punctuation-- then we've got to read your book. But the Human Genome Project was about reading the first copy of the book. Right. LANDER: We're now in the age when biology is about information... ALDA: In February 2001, Eric Lander was the lead author on the scientific paper that announced the first draft of the human genome. This laboratory continues to pour out 50 to 60 million letters of DNA code every day as the details of the human code book are filled in. And unlike the commercial companies that are also sequencing our genes the data streaming out of these machines are free. Every 24 hours, the 50, 60 million letters we produce here get posted on the Web. And they go flying around to databases in Japan and Europe and Washington, and then from there to databases in tens of thousands of biological labs. So in fact, there's this huge information shuffling going on, constantly because if you were studying a particular thing about diabetes you could've searched the world's databases last week to see if there was a gene like what you were looking for and there was nothing. You better make sure you have an automatic program searching again next week because it might have just shown up. And so people have these automatic 'demons' running on their computer. So they say, 'I'm interested in this. Let me know if you should see one.' And then your computer goes 'bong' and says you've got... 'You've got G-mail.' That's... you've got G-mail. That's right. The thing you were looking for just showed up last night, here it is. ALDA: Jim Watson, the first director of the Human Genome Project was convinced it would revolutionize medicine. ALDA: So... tell me about how our lives will be different now medically, do you think? I mean, how revolutionary is this going to be? Well, you know, it's possible to over-hype all this stuff and I think people sometimes have outrageous expectations that there are going to be cures next week from all of this. It's certainly not going to be like that. What it is that's really revolutionary is for the first time we're going to be able to understand the mechanism of how cells work organs work, in a really detailed level. See, we don't actually know what's wrong in most diseases. We can describe that when you have diabetes you have high blood sugar. That's great, but it doesn't tell you what's wrong; what part of the machine is broken. We haven't even had the parts list of the machine. Trying to practice medicine would be like trying to practice auto mechanics when you didn't know what the parts were in the car. You'd never take your car in to an auto mechanic that didn't know what the parts were and how they were connected. Oh, I have many times, actually. Well, probably, yeah. And you know the results. Paid through the nose for it, too. Well, but you take your body in, to medicine and for the last century, we didn't know what the parts were. I mean, we knew what the hearts and the lungs were but not the little molecular machines and how they work so how could we describe what was wrong in diabetes and what's wrong in asthma and what was wrong in hypertension? The real breakthrough of the Genome Project the real guarantee, is we're going to be able to figure out what all those little molecular machines are doing and what goes wrong in disease. It doesn't promise you you'll be able to fix it because of that but the understanding sure beats the ignorance we've had and it's going to transform medicine because for the first time we're going to have met the enemy in disease.

				Fishing for Baby Genes How do genes create a baby? One scientist is using fish to find out.
		Select text to jump ahead in the clip: ALDA: Our next story is also about finding human genes. Now, I always wash... dip my hands here. If you don't mind doing that, that'd be great, because... ALDA: But Nancy Hopkins isn't looking for human genes in humans-- she's looking in fish. These are all... your fish here? Yeah, yes. How many do you have here? HOPKINS: In this room alone... I don't know, we have maybe in here about, I'd say, 75,000. 75,000? 100,000, maybe? Yeah, we have a total of about 150,000 fish. How many did you start with? 23. 23? ALDA: The fish are zebra fish originally from the Ganges River. They're a popular choice for home aquariums for at least one of the reasons they're popular with Nancy-- they thrive in tanks with the right care and attention. HOPKINS: ere's only about a thousand more to go. ALDA: But the main reason Nancy is raising all these zebra fish-- unlikely though it may seem-- is to find the genes that make a baby. HOPKINS: Of course, we would like to use humans... ALDA (laughing): Yes, right... You can't fit them into the tanks. We haven't had any volunteers. ALDA: How close are their genes to ours? I mean, how much can we learn about the development of a baby human from the development of a baby fish of this kind? Alot. Yeah? Yes, we would betotally crushed if it weren't... didn't turn out that the genes were almost identical. This is really hard to understand because if I made a list on a piece of paper of the features that were identical between those fish right there and me... You don't see...? ALDA: I mean, we have eyes; our tails are very different (laughing) our gills are different... HOPKINS: But, they have a head end and a tail end; they have a heart that beats they have a liver, they have a gut and at the cellular level their cells have to do all the same things that your cells do. We really believe that the genes we're going to find for making a baby fish will be many, many of the same as making a baby human. ALDA: A zebra fish egg is mostly yolk. In this speeded-up shot the cells that will become the baby fish are at the top. The cells divide and multiply, and then in just 24 hours they form all the many different types of tissues from which the baby fish is made. Under the microscope the tiny embryos are already wriggling vigorously a day after the eggs were fertilized. So that's the tail, and that's wrapped right around the yolk. There it goes-- whoops. This is the brain. This is the middle of the brain, the hind brain. Whoa, whoa. ALDA: It looks like a little frisky anchovy. Well, thank you for pointing that out. I'd never thought of that. Where's the heart? HOPKINS Just sort of under the chin. ALDA: It's beating fast. HOPKINS: So you can see why it's a terrific animal to study early development because in one day you have that. And one fish-- those little female fish-- can lay several hundred eggs like that in a morning. ALDA: Nancy estimates that of the tens of thousands of zebra fish genes only about 2,400 are actually involved in making a baby fish. Her goal is to find as many of these baby-making genes as she can. She starts by injecting early embryos with a virus that invades the cells and inserts its DNA randomly into the fish's DNA. If a piece of virus happens to land in the middle of a gene that gene will be destroyed. And if the gene was involved in making a body part then the descendants of the fish whose gene was damaged will have a problem. But because Nancy can't know in advance what genes the virus will hit she has to bombard all the genes in thousands of embryos in the hope that occasionally she'll hit something interesting. Then she has to raise and cross-breed thousands of offspring to find out if she did. That's why she needs so many fish. And it's also why much of her lab's time goes into peering at thousands of baby fish looking for her unfortunate victims. It turns out that generally the defects that occur in these little tiny babies actually result in death. Oh, I see. So you see a very specific thing go wrong and then the fish is doomed. ALDA: So far Nancy Hopkins and her colleagues have found more than a dozen specific defects in their zebra fish embryos. HOPKINS: So here's a normal embryo that's two days old. And these two embryos are also two days old but they have a mutation in just one out of maybe their 30,000, 40,000, 50,000 genes. And that one defect is causing this embryo to look like this instead of this. So whenever you take away that gene you get this very specific result. ALDA: To track down the damaged genes, Nancy makes use of the fact that they were damaged in the first place by having a bit of virus DNA stuck into them. Fishing out the virus also fishes out the gene it disrupted. What do you look forward to as the end result of this work? Oh, well, I think there's really two things, you know. One is it has tremendous medical potential, I think because, you know, we're looking for genes through which you really construct the body parts of a vertebrate animal. And so you can imagine that if you have something go wrong with somebody and you wanted to fix it having the genes that make organs grow make tissues, specific cell types grow, and so forth could have tremendous medical application. So that would be terrific if we found the gene that cured some disease. That would be wonderful. But that's sort of a random shot. But in the meantime, you know we're really collecting a list of genes that are essential to build this animal, and we hope in the end to end up with a set of, you know bottles on the shelf and there'll be the hundred genes to make a heart and the 75 genes to make the blood over here 50 for the ear, you know. So it would be all the body parts, in genes. ALDA: Nancy Hopkins was already in mid-career in a different field when she laid everything on the line to invent this way of using fish to look for the genes that make a baby. So perhaps it's no wonder that to her zebra fish are something special. HOPKINS: As scientists we're not supposed to get attached to our animals as individuals but I do love my fish. I must say I do, you know. When I'm upset, I come in the fish room and just... When you're upset you come in and... Just look at the fish, yeah. That's interesting. Hmm... very calming. You can't help wondering what they're thinking about, really.

				A Gene You Won't Forget Scientists can use a gene to improve this insect's memory, and one day, perhaps ours.
		Select text to jump ahead in the clip: ALDA: These are fruit flies-- about as unlike you and me as it's possible for another living creature to be... unless you look at their DNA. Then, as with Nancy Hopkins' zebra fish, the similarity between their genes and ours is downright spooky. For a hundred years fruit flies have been a favorite with geneticists-- and never more so than today. Scores, perhaps hundreds, of human diseases have their genetic counterparts in flies. But of all the insights into ourselves we've gained from these creatures and their genes few are more dramatic than the discovery made by this man, Tim Tully. Tully is fascinated by memory and he's devised an ingenious machine to test the memory skills of fruit flies. He puts several dozen flies into a chamber lined with an electrical coil. The flies are in for an experience they won't forget-- at least for a few minutes. TULLY: Now I'm attaching the voltage source where the flies will get a slight little shock to their feet. They're only receiving about five nano-amps of current which is nothing. Just enough for them to notice, not enough to hurt. ALDA: While they're noticing the tingle in their feet the flies are also noticing something else-- an unusual smell, a chemical scent. The purpose of the experiment is to see how well the flies remember that the tingle and the smell go together. The flies are tapped into a crowded elevator where they wait while Tim attaches two tubes to the basement level of his machine. One tube is fed the odor the flies experienced while being shocked. The other tube gets a different odor. Now comes the test. Tim gently lowers the elevator to a point between the two tubes. The question is, which tube will the flies choose? If they remember the unpleasant experience upstairs they'll avoid that smell down here. If they've forgotten, they could choose either tube. With the experience still fresh in their minds these flies are indeed avoiding the shocking smell. But what Tim really wants to know is how well the lesson stays with them a week or so later in their long-term memory. It turns out it all depends on how they were trained. TULLY: In order for a fly to form a long-term memory of this simple, little odor-shock presentation it has to practice repeatedly. And we've shown clearly with our genetic experiments that if you give the fly ten training sessions of odor-shock pairings and you cram them all together it does not form a long-term memory. You have to give them the right amount of time in between sessions, huh? They have to be spaced out in between. Right? The spaced training is required. There must be a rest interval in between each of those ten training sessions. But is it true that it mustn't be too long a time? Of course. If we were to wait 24 hours between sessions the flies would not form a long-term memory because obviously the memory from one session is completely gone before the next session and that's not going to help. And for this particular task in this fly the optimum rest interval appears to be something like 15 minutes. ALDA: So like most of us, normal flies can't cram nor can they learn from a single experience. So is your needle sharp enough to penetrate that egg? We shall see. ALDA: But this fruit fly egg is getting something extra: a gene called creb. Along with this extra creb gene the flies also get a gene that turns their eyes red so the extra-creb flies-- anesthetized to keep them manageable-- can be easily identified. All flies have a creb gene. Its job is to help convert short-term memories into long-term memories. And when the red-eyed flies with the extra creb gene were tested a week later in Tim's memory machine most of them crowded away from the shock-associated odor no matter how badly they'd been trained. TULLY: For the creb-on flies, they can form a long-term memory after cramming, and even after only one training session. So they have the functional equivalent of a photographic memory. ALDA: As you'll probably not be surprised to learn by now we, too, have a creb gene-- a gene that functions like a switch to turn short-term into long-term memories; from the phone number you just looked up into the phone number you remember all of your life. TULLY: This switch works in both directions. And this is, now, what we think is occurring normally not in a genetically engineered animal but in each of us. B The switch is set somewhere between fully on and fully off. Now, if we can target that switch with a drug... 0Mm-hmm. in principle, we can find drugs that set the switch more toward on and that should facilitate the conversion of short-term to long-term memory. We can think of that as a very therapeutic treatment for those who suffer from Alzheimer's disease and perhaps even from the age-associated memory loss that all of us are going to have eventually. Because what we're doing is we're turning up the gain on how easy it is to convert short-term memory to long-term memory. Where were you for 11 years when I was trying to learn all those lines onMASH? (laughs) I could have just taken one of these creb pills and I'd have been fine. Exactly. And, you know, as we move from considering this kind of drug discovery for clinical applications to lifestyle issues then even the notion that someone could use a drug like this to memorize their lines is not out of the realm of possibility.

				Wisdom of the Worms Mutations produced in the lab make nematode worms live four times longer than normal, leading to a new understanding of how nature governs life spans.
		Select text to jump ahead in the clip: Alda: THIS IS CYNTHIA KENYON A BIOLOGIST AT THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO. IS THAT IT? THERE THEY ARE... THERE THEY ARE. WOW! LOOK AT THEM MOVE! AREN'T THEY PRETTY? Alda: CYNTHIA'S CRAZY ABOUT NEMATODES-- TINY WORMS, SMALLER THAN A GRAIN OF SAND THAT LIVE IN SOIL JUST ABOUT EVERYWHERE. SHE'S FIGURING OUT HOW NEMATODES AGE AND SHE'S PRETTY SURE HUMANS WORK THE SAME WAY. Alda: MOST OF US WOULD THINK HOW IS THAT POSSIBLE? I MEAN, HOW COULD THE WAY A WORM AGES BE ANYTHING LIKE THE WAY WE AGE? THEY HAVE ALL THE SAME KINDS OF TISSUES IN THEIR BODIES THAT WE HAVE IN OUR BODIES. SO, FOR EXAMPLE, THEY HAVE MUSCLE CELLS THAT LET THEM MOVE. THEY HAVE A WHOLE NERVOUS SYSTEM THAT LETS THEM GO TOWARD THINGS THEY LIKE AND GO AWAY FROM THINGS THEY DON'T LIKE. THEY HAVE SKIN. THEY HAVE AN INTESTINE THAT LOOKS A LOT LIKE OUR INTESTINE. SO AT THE LEVEL OF INDIVIDUAL CELLS AND TISSUES THESE ANIMALS ARE VERY SIMILAR TO US. Alda: NORMAL NEMATODE LIFE-SPAN IS JUST TWO WEEKS. Kenyon: THIS IS A BRAND-NEW ADULT WORM. THIS WILL BE MAYBE A COLLEGE GRADUATE-- ABOUT THAT OLD. HOW OLD IS HE? HE'S... IN WORM DAYS, HE'S THREE DAYS OLD AND HE WOULD BE THE EQUIVALENT OF A 20-YEAR-OLD PERSON. SO HE'S PRETTY FRISKY, MOVES AROUND, HAS NICE MUSCLE TONE. YOU CAN SEE. THE WORM HAS NICE MUSCLE TONE. HE DOES! SO HE'S MOVING THROUGH HIS FOOD. THIS IS BACTERIA THAT HE'S... A LAWN OF BACTERIA. THAT'S A NICE, SINUOUS MOVEMENT. WHAT DOES AN OLD GUY LOOK LIKE? OKAY, NOW, I'LL GET AN OLD WORM FOR YOU. HERE'S A NICE... HERE'S SOME NICE OLD WORMS. HERE'S A PAIR OF THEM. BOY, THEY'RE JUST SITTING OUT IN THE SUN! LOOK AT THEM! LOOK AT THEM-- THERE ARE TWO OF THEM. THEY'RE ON THEIR LAWN CHAIRS. THEY ARE-- OR MAYBE EVEN IN A NURSING HOME. AND THIS WORM IS STILL A LITTLE BIT ACTIVE BUT IT'S NOTHING LIKE A YOUNG WORM AND LOOK AT ITS BODY-- SEE THIS BIG GAP HERE AND THESE LITTLE POCKMARKS? IT DOESN'T LOOK YOUNG ANYMORE. IT LOOKS VERY OLD NOW. AND ACTUALLY WHAT I THINK IS REALLY INTERESTING IS THAT ANYONE IN THE WORLD LOOKING AT THESE WORMS CAN SEE THAT THEY LOOK KIND OF OLD. IT'S... SO IN OTHER WORDS THERE'S SOMETHING ABOUT THE AGING PROCESS THAT SPEAKS TO YOU DIRECTLY FROM AN ANIMAL OF ANY TYPE. Alda: IN A SERIES OF EXPERIMENTS THAT BECAME INSTANT CLASSICS CYNTHIA HAS MADE WORMS THAT LIVE TWICE AS LONG AS NORMAL. FIRST SHE GAVE NORMAL WORMS A BATH IN A RATHER UNPLEASANT CHEMICAL THAT CAUSES RANDOM CHANGES, OR MUTATIONS IN THE GENETIC MATERIAL INSIDE THE WORMS' CELLS. NEXT SHE LABORIOUSLY PLACED THOUSANDS OF SINGLE WORMS ONTO THEIR OWN INDIVIDUAL DISHES. NOW SHE COULD FOLLOW EACH WORM OVER TIME GENERATION AFTER GENERATION. MOST WORMS DIED OR LIVED SHORTER LIVES BECAUSE OF THEIR MUTATIONS. BUT IN A FEW, THERE WAS A SINGLE CHANGE-- A CHANGE IN ONE GENE-- THAT LED TO LONGER LIFE. SO NOW, LIVING IN THE INCUBATOR IN CYNTHIA'S LAB IS A STRAIN OF MUTANT WORM THAT LIVES FOUR WEEKS, RATHER THAN TWO. IT'S ASTONISHING TO SEE A LIVELY, YOUNG-LOOKING WORM THAT'S THE SAME AGE AS THE OLD FOLKS WE'D SEEN EARLIER. OH, MY GOD, THAT REALLY IS... THIS IS A MUTANT WORM. THIS IS STRIKING. THIS IS THE SAME AGE! IT'S THE SAME AGE. I'M NOT KIDDING YOU. LOOK AT THAT. I MEAN, IT DOESN'T LOOK LIKE... I NEVER LOOKED AT THESE WORMS BEFORE BUT THIS LOOKS... IT LOOKS GREAT. TO MY EYE, THIS LOOKS THE SAME AS THE THREE-DAY-OLD... WELL, IT'S A LITTLE DIFFERENT. HOW IS IT DIFFERENT? SHOW ME HOW IT'S DIFFERENT. IT'S A LITTLE BIT BIGGER, A LITTLE SLOWER BUT, YOU KNOW, IT'S MUCH YOUNGER IN SPIRIT THAN THAT WORM WE JUST SAW THAT'S FOR SURE. ISN'T THAT AMAZING? IT IS AMAZING. I MEAN, IT'S JUST UNBELIEVABLE. YOU CHANGE ONE GENE AND ESSENTIALLY YOU CURE THIS DISEASE OF AGING IF YOU WANT TO PUT IT THAT WAY. I'M TAKING THIS VERY PERSONALLY HERE FOR A MINUTE BECAUSE... THIS... WELL I'D LIKE TO LIVE TO ABOUT 106 AT LEAST THAT'S WHAT I'VE ALWAYS THOUGHT BUT NOW I MAY SWITCH. MAYBE I'M TOO MODEST-- MAYBE I SHOULD GO FOR 140 OR SO. WHY NOT? THAT'S WHAT I WANT TO ASK YOU, WHY NOT? BECAUSE WHAT I WANT TO KNOW IS-- THIS GUY IS 12 DAYS OLD. HE'S STILL THRIVING AT 12 DAYS-- 12 OUT OF A 14-DAY USUAL LIFE SPAN. HE'S GOING TO GO ON ANOTHER TWO WEEKS, RIGHT? YEAH. NOW, IN THOSE TWO WEEKS HOW MUCH OF THOSE TWO WEEKS WILL BE VIGOROUS LIKE THIS? WHEN'S HE GOING TO START TO ACT LIKE A 100-YEAR-OLD OR 110-YEAR-OLD PERSON? WHAT DO YOU OBSERVE? I WOULD SAY THAT IN ABOUT ONE MORE WEEK THIS ANIMAL WILL BE STILL NOT LOOKING AS BAD AS THE NORMAL WORMS THAT I JUST SHOWED YOU-- THE NORMAL 12-DAY-OLD WORMS-- BUT THEY'LL BE MUCH SLOWER. THEY'LL BE WALKING AND NOT RUNNING. Alda: IN OTHER WORDS, EVERYTHING TAKES TWICE AS LONG-- YOUTH, MIDDLE AGE AND OLD AGE. THIS REALLY COULD HAPPEN WITH PEOPLE SOMEDAY BECAUSE CYNTHIA'S RAPIDLY FIGURING OUT HOW THE LIFE-SPAN SYSTEM WORKS. HERE IT IS. WHAT IS THIS, LIKE A THOUSAND TIMES BIGGER THAN IT OUGHT TO BE? EVEN MORE THAN THAT, I THINK BECAUSE THE NORMAL WORM YOU CAN HARDLY SEE SO THIS IS A ZILLION TIMES LARGER. A ZILLION. AH, I KNEW THERE WAS A NUMBER. Alda: IN NEMATODES, LIFE-SPAN IS REGULATED BY HORMONE MESSENGERS THAT CIRCULATE IN THE BODY AND LAND ON RECEPTORS-- LIKE THIS BLUE MUSHROOM. THIS RED THING HERE IS A CELL. AND THE WORM IS ACTUALLY FULL OF MANY CELLS SO THIS IS JUST ONE OF THEM. YEAH. THE RECEPTOR SITS IN THE EDGE OF THE CELL AND ITS JOB IN THE ANIMAL IS TO RECEIVE SIGNALS FROM THE OUTSIDE AND THE SIGNALS THAT IT RECEIVES ARE HORMONES SO THIS IS A HORMONE. OKAY. WE HAVE LOTS OF HORMONES IN OUR BODIES CONTROLLING ALL ASPECTS OF OUR GROWTH AND OUR PHYSIOLOGY. IN THE NORMAL WORM WHERE THE HORMONE IS BOUND TO THE RECEPTOR THE CONSEQUENCE IS THAT THE WORMS HAVE A SHORT LIFE-SPAN. Alda: THE MUTATION THAT EXTENDS LIFE CHANGES THE SHAPE OF THE RECEPTOR SO THE HORMONE'S BLOCKED. AND SO THE HORMONE CAN'T FIT INTO ITS NORMAL SPOT. SEE, LIKE THAT-- IT CAN'T FIT IN THERE AND AS A CONSEQUENCE, THE ANIMAL LIVES LONGER. DO YOU KNOW WHY? WE DON'T KNOW ALL THE DETAILS BUT WE DO KNOW THAT ONE THING THAT'S VERY IMPORTANT ARE THESE LITTLE ORANGE BALLS HERE. THESE, IT TURNS OUT WE CAN CALL THESE "FOUNTAIN OF YOUTH" BALLS. Alda: WITH THE RECEPTOR BLOCKED, THE CELL MAKES MORE YOUTH CHEMICAL AND THAT'S THE STUFF THE WORM NEEDS TO LIVE. BUT IN NORMAL WORMS WITH WORKING RECEPTORS THE FOUNTAIN OF YOUTH DRIES UP. WHY WOULD NATURE ARRANGE IT THAT WAY IF IT'S GOING TO LEAD TO AN EARLY DEATH? IS THERE SOME ADVANTAGE TO THIS NEMATODE THIS INDIVIDUAL NEMATODE, DYING IN TWO WEEKS INSTEAD OF WHAT YOU CAN ARRANGE, FOUR WEEKS? WE DON'T KNOW. WE DON'T KNOW WHY THE WORM HAS ITS OWN GRIM REAPER INSIDE OF IT. Kenyon: SO HERE GOES. I'M GOING TO START SHOOTING THE LASER AT IT. NOW, THE WAY I DO THAT IS WITH A LITTLE FOOT PEDAL HERE. Alda: CYNTHIA HAS DISCOVERED A SECOND LIFE-SPAN REGULATION SYSTEM IN NEMATODES THIS TIME BY DISRUPTING CELLS USED IN REPRODUCTION. SHE DELICATELY KNOCKS OUT THE CELLS USING A TINY LASER. I THINK I'VE KILLED IT NOW, YES. HERE'S THE CELL I'VE BEEN SHOOTING AT. WHEN I STARTED OFF IT LOOKED A LOT LIKE THIS CELL WITH A NICE DISH-SHAPED CENTER BUT NOW YOU SEE IT'S GONE-- THERE'S NO ROUND CIRCLE. Alda: WORMS WITH REPRODUCTIVE CELLS DESTROYED ALSO DOUBLE THEIR LIFE-SPANS, AND THE MECHANISM IS JUST LIKE THE FIRST SYSTEM CYNTHIA DISCOVERED. IN THIS CASE THE WORMS NO LONGER MAKE A SECOND KIND OF MESSENGER HORMONE AGAIN RESULTING IN MORE YOUTH CHEMICAL BEING MADE INSIDE THE CELLS. SO WHAT HAPPENS WHEN ONE WORM HAS BOTH LIFE-SPAN SYSTEMS BLOCKED? Kenyon: WHAT WE FOUND IS THAT IT LIVES TWICE AGAIN AS LONG. YOU'RE KIDDING! YEAH, IT'S A VERY AMAZING RESULT. SO IT LIVES NOW... INSTEAD OF A HUMAN LIVING LIKE NOT 90 YEARS BUT 180 IT'S LIKE LIVING 360 YEARS. DO YOU SEE WHAT I'M SAYING? YOU'RE DOUBLING THE DOUBLING OF THE LIFE-SPAN. Alda: IT'S LIKELY THAT ALL LIVING THINGS USE THESE SAME HORMONE MESSENGERS TO REGULATE LIFE-SPAN. THE FASCINATING THING IS THAT THE HORMONES ARE RELATED TO INSULIN WHICH IS MADE BY THE BODY WHEN WE EAT FOOD. SO MAYBE THAT'S WHY RESTRICTING CALORIE INTAKE LENGTHENS LIFE. SOMETHING LIKE A LONG-LIFE PILL COULD BE POSSIBLE ONCE WE FULLY UNDERSTAND THESE SYSTEMS AND SOMEDAY WE SURELY WILL, THANKS TO CYNTHIA KENYON. Alda: BEFORE YOU DID THIS WORK DID YOU HAVE AN AGE THAT YOU THOUGHT YOU MIGHT LIVE TO AND NOW HAVE YOU CHANGED YOUR MIND ABOUT WHAT THAT AGE MIGHT BE? YEAH, I'M MUCH MORE... WELL, I HAVE TO TELL YOU, I HAVE A RETIREMENT ACCOUNT. SO THAT MEANS THAT AT SOME LEVEL I THINK I MIGHT HAVE TO RETIRE AT SOME POINT SO PART OF ME IS LIVING IN THE REAL WORLD. ON THE OTHER HAND, I HAVE AN IMAGINATION THAT I MIGHT NOT HAVE TO USE IT FOR A VERY LONG TIME. IT COULD GET REALLY BIG! ( thunder ) Alda:

Take a look at these related stories from the Frontiers Archive:

				Iceland Genes Their small homogenous population and excellent medical records makes Icelanders the ideal subjects of genetic studies.
		Select text to jump ahead in the clip: THE MOST FAMOUS VOYAGE BY A NORSEMAN IN THE VIKING AGE WAS THAT OF LEIF ERIKSON, ALSO KNOWN AS LUCKY WHO DISCOVERED VINLAND, THE LAND WE NOW CALL AMERICA AROUND THE YEAR 1000. BUT THIS SCULPTURE CELEBRATES ANOTHER, EVEN EARLIER VOYAGE BY THE NORSEMAN INGOLFUR ARNARSON IN 874. NEVER HEARD OF HIM? WELL, THAT MEANS YOU'VE NEVER BEEN HERE TO REYKJAVIK THE CITY HE FOUNDED AS THE OFFICIAL FIRST SETTLER OF ICELAND. FOLLOWING INGOLFUR WHO MUST HAVE BEEN ONE TERRIFIC REAL ESTATE SALESMAN ABOUT 25,000 OF HIS FELLOW NORSEMEN AND NORSEWOMEN SETTLED HERE IN THE NEXT 50 YEARS OR SO. MOST OF TODAY'S ICELANDERS WHO NUMBER ABOUT A QUARTER OF A MILLION ARE DIRECT DESCENDANTS OF THOSE EARLY SETTLERS AND THEY LOOK IT, TOO. BUT IT'S NOT JUST THE FIRST SETTLERS AND THEIR MOST RECENT DESCENDANTS WHO CAN BE COUNTED. Alda: IS IT ACTUALLY TRUE THAT YOU KNOW ABOUT HOW MANY PEOPLE HAVE EVER LIVED IN ICELAND? Man: YES. HOW DO YOU KNOW? BECAUSE WE KNOW THE GENEALOGY. WE KNOW THE NAMES. YOU KNOW THE NAMES OF ALL THE PEOPLE WHO EVER LIVED? YEAH, WE KNOW THE NAMES. WE KNOW WHO WERE THEIR FATHERS AND MOTHERS AND DAUGHTERS AND SONS. WE KNOW WHERE THEY LIVED. THAT'S REMARKABLE. HOW MANY PEOPLE EVER LIVED HERE? THREE-QUARTERS OF A MILLION OR SO. BUT THREE-QUARTERS OF A MILLION-- THAT'S, LIKE, HOW MANY PEOPLE IN THE WORLD ARE BORN EVERY FEW DAYS, PROBABLY. YEAH, BUT THEY ARE NOT ICELANDERS. ( both laugh ) THE MANUSCRIPTS IN THIS BUILDING WERE COLLECTED FROM WHERE? THEY WERE COLLECTED FROM... Alda: KARI STEFANSSON HAS BROUGHT ME TO SEE FIRSTHAND HOW THE ICELANDERS' OBSESSION WITH GENEALOGY BEGAN WHICH TURNED OUT TO BE IN ANOTHER ICELANDIC TRADITION-- THE WRITING DOWN OF HEROIC TALES, SAGAS IN BOOKS DATING BACK TO THE SETTLEMENT OF THE COUNTRY. Alda: WHAT IS THIS BOOK? THIS IS A MANUSCRIPT OF... ONE OF THE OLDEST MANUSCRIPTS OF THE ICELANDIC SAGAS. NOW, WHAT'S IN THE SAGAS? THE SAGAS ARE... ACCORDING TO THE OLD MYTHS ARE STORIES OF THE SETTLEMENT OF ICELAND OR THE STORY OF THE SETTLERS. THE BOOKS TELL FROM VERY COMPLEX FEUDS AND IT'S VERY IMPORTANT TO KNOW WHO IS RELATED TO WHOM TO BE ABLE TO UNDERSTAND THE STORY. ALMOST ALL OF THEM BEGIN WITH PAGE AFTER PAGE OF GENEALOGY WHICH IS SORT OF, IN MY MIND, AT LEAST THE BEGINNING OF THE GREAT INTEREST IN GENEALOGY THAT HAS PREVAILED IN ICELAND EVER SINCE THEN. Alda: THIS BOOK, FOR INSTANCE, IS A COPY OF THE BOOK OF SETTLEMENT WHICH LISTS THE NAMES OF THE ORIGINAL SETTLERS AND THEIR IMMEDIATE DESCENDANTS. AND THIS YOUNG MAN, WHOSE NAME IS HREINN STEFANSSON IS ONE OF THE MANY PRESENT-DAY ICELANDERS WHO CAN, ASTONISHINGLY, TRACE THEIR ANCESTRY ALL THE WAY BACK TO THE BOOK OF SETTLEMENT. HREINN STEFANSSON'S LINEAGE IN FACT GOES BACK 31 GENERATIONS TO THE YEAR 860 A. D. AND ONE THORDUR VIKINGSSON THE SON OF A VIKING KING. BOTH HREINN AND THE COMPUTER PROGRAM THAT TRACKED HIS ANCESTRY ARE EMPLOYED IN A NEW COMPANY FOUNDED TO CAPITALIZE ON ICELAND'S UNIQUELY INTIMATE GENETIC HERITAGE. CALLED DECODE GENETICS AND EMPLOYING MOST OF ICELAND'S YOUNG GENETICS RESEARCHERS THE COMPANY IS IN THE THICK OF THE WORLDWIDE HUNT FOR GENES THAT CAUSE HUMAN DISEASE. ACCORDING TO KARI STEFANSSON, DECODE'S FOUNDER IT'S ALREADY HOT ON THE HEELS OF SEVERAL SUCH GENES INCLUDING ONE INVOLVED IN MULTIPLE SCLEROSIS. Alda: WHAT ARE THESE PEOPLE DOING HERE? I SEE PEOPLE WORKING WITH VIALS. HOW ARE THEY FINDING OUT ABOUT MULTIPLE SCLEROSIS? THEY HAVE FOUND GENES AND NOW THEY ARE USING SPECIFIC METHODS TO LOOK FOR MUTATIONS IN THESE GENES THAT ARE ONLY FOUND IN PATIENTS WITH THE DISEASE AND ARE NOT FOUND IN INDIVIDUALS WHO DO NOT HAVE THE DISEASE. WHAT ARE THEY DOING HERE? THEY ARE ISOLATING DNA. NOW, THIS IS BLOOD FROM ONE PERSON? YES. AND YOU... DO YOU KNOW THAT PERSON'S MEDICAL HISTORY? UM... Woman: I DO, YES. SHE KNOWS THIS PERSON'S MEDICAL HISTORY. Alda: AND THIS IS WHERE ICELAND'S GENETIC ISOLATION AND DETAILED GENEALOGIES BECOME INVALUABLE. A MUTATION CAUSING MULTIPLE SCLEROSIS IN ONE ICELANDER IS MOST LIKELY THE SAME MUTATION THAT CAUSES THE DISEASE IN ANOTHER BECAUSE EACH INHERITED IT FROM THE SAME ANCESTOR. THIS MAKES TRACKING AND FINDING SUCH A DAMAGED GENE MUCH EASIER THAN IT IS IN LARGER, MORE DIVERSE POPULATIONS. WHAT HAPPENS IF YOU FIND THIS GENE, THEN WHAT? THEN WE KNOW WHAT CAUSES THE DISEASE, AND OUR ASSUMPTION IS THAT KNOWLEDGE OF THE CAUSE OF THE DISEASE IS ALWAYS GOING TO HELP US BOTH TO FIND THE CURE FOR THE DISEASE AND FIND WAYS OF ACCURATELY DIAGNOSING IT. HOW WILL THIS COMPANY PROFIT FROM YOUR WORK? I LOOK AT THIS FIRST AND FOREMOST AS A COMPANY OF ICELANDERS FOR ICELANDERS AND THE COMPANY BENEFITS BY HAVING AN OPPORTUNITY TO DO EXTREMELY GOOD SCIENCE AND CONTRIBUTING TO CURING DISEASES. ECONOMICALLY WE WILL BENEFIT BY CONTRACTING WITH LARGE PHARMACEUTICAL COMPANIES THAT EVENTUALLY WILL DEVELOP THE MEDICATIONS FOR THE TREATMENT THAT WILL BE DERIVED FROM THE DISCOVERY OF THESE GENES. Alda: DURING MY BRIEF VISIT I FOUND ICELANDERS TO BE A HIGHLY EDUCATED, CARING PEOPLE WHO, BECAUSE THERE ARE SO FEW OF THEM ALL SEEM TO KNOW ONE OTHER. AND NOW THESE FEW THOUSAND DESCENDANTS OF THE VIKINGS MAY BE GIVING THE REST OF US ON THE PLANET SOMETHING UNIQUE-- INSIGHT INTO DISEASES THAT PLAGUE MILLIONS. Alda: IT SEEMS THAT YOUR ABILITY TO FIND THE SOURCES OF THESE DISEASES IS CONNECTED TO THE... THE KIND OF LONELINESS OF THIS ISLAND THE PEOPLE ON THIS ISLAND. IT'S INTERESTING YOU THINK ABOUT THIS IN A SOCIAL CONTEXT; THAT THIS ISOLATION THAT KEPT THE NATION GENETICALLY HOMOGENEOUS WAS ONE OF THE MAJOR REASONS AS TO WHY THE NATION WAS DESPERATELY POOR FOR ALL OF THE CENTURIES. AND NOW THERE'S THE CONSEQUENCE OF THIS: THE SAME ISOLATION HAS BECOME A NATURAL RESOURCE THAT WE CAN MINE. YOU COULD ARGUE THAT OUR WORK ON GENETICS IS A SEARCH FOR POETIC JUSTICE WHEN IT COMES TO THIS ISOLATION. ICELAND IS A VERY YOUNG COUNTRY AND NOT ONLY BECAUSE PEOPLE HAVE BEEN HERE

				The Clock of Life The internal mechanism, telomeres, that makes cells age and die has been discovered. Soon we may be able to keep our bodies’ cells young forever.
		Select text to jump ahead in the clip: AND IT'S BEEN THAT WAY FOR THE SEVERAL HUNDRED THOUSAND YEARS WE'VE BEEN ON THIS EARTH. NOW SUDDENLY WE'VE BEGUN TO GLIMPSE NATURE'S MACHINERY OF AGING INSIDE OUR CELLS. THROUGHOUT LIFE CELLS CONSTANTLY REJUVENATE THROUGH DIVISION TO KEEP OUR BODIES HEALTHY. IN THE '60s, IT WAS DISCOVERED THERE'S A LIFETIME LIMIT OF ABOUT 50 DIVISIONS AND THEN CELLS DIE OR START CAUSING TROUBLE. BUT WHAT IF WE COULD AVOID THIS LIMIT AND LET CELLS DIVIDE FOREVER? THAT'S THE EXTRAORDINARY IDEA WE'LL EXPLORE IN THIS STORY. WE START WITH A HIGHLY MAGNIFIED PICTURE OF HUMAN CHROMOSOMES-- THE STRUCTURES INSIDE CELLS MADE OF DNA. ON THE ENDS OF EACH CHROMOSOME ARE THINGS CALLED TELOMERES-- HIGHLIGHTED HERE WITH A SPECIAL DYE. IN THE 1980s, IT WAS DISCOVERED THAT TELOMERES GET SHORTER EVERY TIME A CELL DIVIDES UNTIL THE TELOMERES DISAPPEAR ALMOST ENTIRELY. I'M VISITING THE GERON CORPORATION A SMALL BIOTECH COMPANY IN MENLO PARK, CALIFORNIA. THEIR CHIEF SCIENTIST, CAL HARLEY IS THE MAN WHO MADE THIS DISCOVERY ABOUT TELOMERES. Harley: THE LITTLE PLASTIC TIP AT THE END OF A SHOELACE IS LIKE THE TELOMERE. IT FUNCTIONS TO SORT OF PROTECT THE END OF THE CHROMOSOME-- OR IN THIS CASE THE END OF THE SHOELACE-- FROM FRAYING AND NOT BEING ABLE TO FUNCTION. Alda: IT SEEMS TO ME THAT THIS THING THAT'S ACTING LIKE A TELOMERE WOULD BE USEFUL FOR ELIMINATING OR HOLDING OFF FRAYING... FOR A LONG TIME. IT CAN GET VERY, VERY, VERY, VERY SHORT... RIGHT. AND IT'LL STILL DO THE JOB. IS THE TELOMERE LIKE THAT? THERE'S ACTUALLY A CRITICAL POINT WHEN THE TELOMERE GETS DOWN TO MAYBE LESS THAN FIVE PERCENT OF ITS LENGTH AT BIRTH WHERE, AT THAT POINT, THERE IS A VERY STRONG SIGNAL THAT THIS CELL IS IN DANGER BECAUSE THERE IS SOME DAMAGED DNA NOW BEING EXPOSED. Alda: CAL FOUND THAT CELLS STOP DIVIDING WHEN TELOMERES RUN OUT. THEY'RE LIKE THE CLOCK OF LIFE. ANOTHER BREAKTHROUGH CAME WHEN GERON LOCATED THE EXACT SECTION OF DNA-- OR THE GENE-- THAT GOVERNS THE MANUFACTURE OF TELOMERES IN CELLS. IT'S CALLED THE TELOMERASE GENE. AT A BOSTON HOSPITAL RONALD DEPINHO IS WORKING WITH THIS GENE TO EXPLORE WHAT HAPPENS WHEN TELOMERES FINALLY RUN OUT. LET'S TAKE A LOOK. Alda: THEY'VE BRED A SPECIAL STRAIN OF MOUSE WHICH HAS NO TELOMERASE GENE. BECAUSE MICE NORMALLY HAVE MUCH LONGER TELOMERES THAN PEOPLE IT'S TAKEN A FEW GENERATIONS OF THE LAB MICE TO GET DOWN TO SHORT TELOMERES. NOW IT'S GETTING INTERESTING. WHAT WE SEE ARE SOME OBVIOUS EXTERNAL MANIFESTATIONS OF SHORT TELOMERES. WE HAVE A NORMAL MOUSE HERE WITH A QUITE NORMAL-LOOKING COAT COLOR THAT HAS A NICE BLACK SHEEN TO IT. AND THIS IS A MOUSE OF EQUIVALENT AGE THAT HAS SHORT TELOMERES AND WHAT WE SEE ARE SOME OBVIOUS HAIR GRAYING COMPARED TO THE NORMAL COAT COLOR OF THIS MOUSE HERE-- SHORT TELOMERES, NORMAL TELOMERES. AND STILL OTHERS HAVE THE ADDITIONAL PROBLEM WHERE THEY HAVE ACCELERATED HAIR LOSS. Alda: SINCE HAIR NEVER STOPS GROWING HAIR CELLS WOULD BE AMONG THE FIRST WHOSE TELOMERE CLOCK RUNS OUT. THIS IS SOME OF THE FIRST SOLID EVIDENCE THAT TELOMERES CAN AFFECT AT LEAST THE SYMPTOMS OF AGING. FOR THE FIRST TIME, WE CAN SHED SOME LIGHT ON THE TRAGIC DISEASE OF PROGERIA-- PREMATURE AGING. THESE ARE CHILDREN, ALL UNDER 12 YEARS OLD ATTENDING AN ANNUAL GET-TOGETHER OF THE 40 OR SO PROGERIA KIDS IN THE WORLD. BONJOUR. CA VA? Alda: PEDIATRICIAN MICHAEL FOSSEL STUDIES THE DISEASE. Fossel: THESE KIDS ARE BORN OLD. THEY HAVE NORMAL CHILDHOOD MINDS. THEY'RE BRIGHT, THEY'RE FUNNY. THEY'RE TYPICAL OF ANY OTHER CHILD BUT THEY ALSO GET ANGINA AND THEY ALSO GET HEART ATTACKS IN THE PLAYGROUND AND THEY GET ARTHRITIS. THEY HAVE OLD SKIN. THEY DON'T MOVE WELL. THEY'RE SHRIMPY, YOU KNOW BUT OTHERWISE, THEY'RE NORMAL KIDS. Alda: PROGERIA KIDS HAVE THE DISEASES OF OLD AGE AND WE NOW KNOW THEY HAVE SOMETHING ELSE-- SHORT TELOMERES. SHORT TELOMERES MEAN CELLS CAN'T DIVIDE AND REPAIR DAMAGE SO DISEASE STARTS. NOW AT LEAST THE DOOR IS OPEN TO A GENETIC CURE FOR THESE KIDS. YOU CAN GET AN IDEA HOW SUCH A CURE MIGHT WORK BACK AT GERON. CAL HARLEY SHOWED ME UNDER THE MICROSCOPE WHAT HUMAN EYE CELLS LOOK LIKE WHEN THEY'RE YOUNG, HEALTHY AND STILL ABLE TO DIVIDE. SO ALAN, HERE'S AN EXAMPLE OF A YOUNG CELL WITHIN THAT POPULATION THAT IS GOING THROUGH THE PROCESS OF DIVISION. Alda: THESE ARE THE CELLS DIVIDING, USING UP THEIR TELOMERES. NOW TAKE A LOOK AT OLD CELLS WITH NO TELOMERES LEFT. THEY'RE LITERALLY BLOATED-- THEY'VE LOST THEIR YOUTHFUL LINES. ABNORMAL CELLS LIKE THESE CAUSE THE SYMPTOMS OF OLD AGE: CATARACTS, GRAY HAIR, WRINKLED SKIN, ARTHRITIS, EVEN CANCER. Alda: NOW, WHAT IF YOU TOOK TELOMERASE AND GOT IT IN THERE? COULD YOU BUILD UP THE ENDS-- THE TIPS OF THE SHOELACES? THAT'S THE MILLION- DOLLAR QUESTION IS CAN WE PREVENT THIS PROCESS FROM HAPPENING OR, IN PART, REVERSE IT? Alda: CAL INVITED ME TO ANSWER THE MILLION-DOLLAR QUESTION FOR MYSELF. USING THE NORMAL PROCEDURES OF THE GENETIC ENGINEERING LAB I SET ABOUT INSERTING THE TELOMERASE GENE INTO OLD HUMAN EYE CELLS. AND I JUST PRESS IT ALL THE WAY DOWN... Alda: THIS IS AN EXPERIMENT FIRST DONE AT GERON JUST 18 MONTHS EARLIER. THIS IS WHY WE USE PLASTIC. I'LL JUST TAKE THAT ONE FOR YOU. ALL RIGHT, THANK YOU. SEE, WHEN I HAD CHEMISTRY I DIDN'T HAVE A PERSONAL COACH LIKE THIS. I WOULD HAVE DONE MUCH BETTER. Alda: THE FINAL STEP IS TO FORCE THE NEW GENES INTO THE OLD CELLS WITH A FRANKENSTEIN-LIKE ELECTRIC SHOCK. THERE, AND I PUSH THIS IN. ( machine humming ) Alda: AND BINGO! IT WORKS. YOU GET NEW, YOUTHFUL CELLS. Alda: I'M KIND OF SURPRISED AT HOW VIVID THIS IS. YEAH. THE FIRST TIME WE SAW IT WE WERE VERY MUCH SURPRISED. EVEN THOUGH THIS IS WHAT WE WERE PREDICTING AND HOPING FOR THE IMPACT OF THIS IS DRAMATIC. SOME OF THESE CELLS HAVE BEEN GOING NOW FOR 300 DOUBLINGS WHERE THE NORMAL CELLS AGE AT 50. THEY'RE STILL READY FOR MORE. YEAH. THAT'S WHY WE SOMETIMES CALL THEM IMMORTAL BUT A MORE ACCURATE TERM WOULD BE "INDEFINITE DIVISION CAPACITY. " SO IF THIS WERE HAPPENING, LET'S SAY IN THE SKIN ON MY FACE... ( both laughing ) WHAT DO YOU MEAN? YOU HAVE TO UNDERSTAND, I'M AN ACTOR, YOU KNOW DURING MOST OF THE WEEK. SO IF THIS WERE HAPPENING IN THE SKIN ON MY FACE THE, UH... BAGS UNDER MY EYES WOULD TEND TO GO AWAY BY THEMSELVES APPARENTLY. Alda: RIGHT NOW WE DON'T KNOW THE ANSWER TO MY QUESTION. WE CAN REJUVENATE CELLS IN A DISH BUT THAT'S NOT THE SAME AS REPAIRING TISSUE DAMAGE ON A LARGE SCALE. HERE AT U. C.L.A. RITA EFFROS IS WORKING ON ONE OF THE FIRST APPLICATIONS OF LARGE-SCALE CELL REPAIR. THE GOAL IS TO REJUVENATE THE CELLS OF THE BODY'S IMMUNE SYSTEM IN THE SAME WAY I DID AT GERON WITH EYE CELLS BY ADDING THE TELOMERASE GENE. IF OLD FOLKS HAD YOUNG AND VIGOROUS IMMUNE SYSTEMS THEY'D OBVIOUSLY BE ABLE TO FIGHT OFF DISEASES MORE EFFECTIVELY. Effros: WHAT WE'RE HOPING TO DO IS EXTEND THE LIFE OF ELDERLY PEOPLE TO THE MAXIMUM LIMIT THAT WE NOW KNOW IS THE HUMAN LIMIT WHICH IS APPROXIMATELY 120 YEARS. SO WE'RE HOPING THAT A PERSON WHO'S 100 OR 105 WOULD RESPOND BETTER TO AN INFECTION AND THEREFORE NOT DIE FROM THAT INFECTION AND CONTINUE LIVING. Alda: THIS WORK IS NOW LOOKING VERY PROMISING. FOR EXAMPLE, THIS IS THE RESPONSE OF A REJUVENATED IMMUNE SYSTEM TO A VIRUS. THE DARK PATCHES ARE DENSE SWARMS OF IMMUNE CELLS ATTACKING THE INTRUDER. COMPARE THAT TO THE WEAK RESPONSE OF A NORMAL 80-YEAR-OLD'S IMMUNE SYSTEM. SOMETIME IN THE NEXT FEW YEARS GETTING AN IMMUNE SYSTEM BOOST COULD BECOME ROUTINE FOR PEOPLE OVER, SAY, 60. MANY MORE PEOPLE MIGHT CONQUER DISEASE AND REACH THE 120-YEAR LIMIT. BUT CAN WE GO FURTHER? WILL WE BE ABLE TO LIVE 150 OR 200 YEARS? IS THAT POSSIBLE? THERE'S NO REASON WHY GENETICALLY WE CAN'T HAVE A LIFE-SPAN THAT COULD BE 100, 200, 300 YEARS. THERE'S JUST NO THEORETICAL REASON THAT THAT IS IMPOSSIBLE. Alda: TO DOUBLE OR TRIPLE HUMAN LIFE-SPAN IS AN ASTONISHING IDEA BUT DON'T DISMISS IT BEFORE YOU SEE OUR NEXT STORY.

				Bypass Genes Gene therapy promotes new vessel growth, and allows a woman with blocked arteries in her leg to walk again.
		Select text to jump ahead in the clip: THIS SHOPPING MALL IN NATICK, MASSACHUSETTS IS ALREADY HUMMING WITH ACTIVITY. ONE OF THE MOST ENTHUSIASTIC OF THE MALL-WALKERS USED TO BE LILLIAN COOPER. Cooper: I STARTED ABOUT SEVEN YEARS AGO AND I COULD WALK FIVE MILES EVERY MORNING. I DON'T WANT TO BE IMMODEST, BUT I WAS A GOOD MALL-WALKER. I WAS USUALLY AT THE HEAD OF THE GROUP. Alda: BUT FOR TWO YEARS NOW, LILLIAN HAS BEEN SIDELINED BY A BADLY NARROWED ARTERY IN HER LEFT LEG. Cooper: IF I DON'T FIND A WAY TO GET IT FIXED I'M GOING TO LOSE THE LEG. I'VE BEEN ADVISED OF THAT BY TWO DOCTORS AND I'M NOT READY FOR THAT. Alda: LILLIAN HAS ALREADY HAD ALL THE STANDARD THERAPIES FOR HER BLOCKED ARTERY. BUT NOW THERE'S SOMETHING NEW, INVOLVING A FORM OF THERAPY MANY BELIEVE WILL REVOLUTIONIZE MEDICINE IN THE 21st CENTURY. AT BOSTON'S ST. ELIZABETH'S HOSPITAL HER DOCTOR IS JEFFREY ISNER. NOW, WE'RE ONLY NUMBING THAT BECAUSE WE LIKE YOU, LILLIAN. ( chuckles ) Alda: SHE'S BEEN THROUGH THIS PROCEDURE OFTEN. A CATHETER IS BEING SLIPPED INTO THE MAIN ARTERY OF HER LEG AND THEN A DYE THAT SHOWS UP ON X-RAYS IS INJECTED. THE RESULTING ANGIOGRAM SHOWS THE DYE REACHING THE BLOOD VESSELS IN HER LOWER LEG. Isner: THIS IS WHERE THE PROBLEM IS. IT TAKES A LONG TIME FOR THAT DYE TO WIND ITS WAY ALL THE WAY DOWN TO HER CALF MUSCLE AND FOOT. THAT'S WHY SHE'S HAVING ALL THE PAIN. AND SO THE NEED HERE IS TO FIND A WAY TO SOMEHOW DELIVER A SIGNIFICANTLY LARGER VOLUME OF BLOOD FLOW DOWN TO THE LOWER LEG. SO, LILLIAN, THE ANGIOGRAM... Alda: RESTORING BLOOD FLOW IN A BLOCKED BLOOD VESSEL IS USUALLY ATTEMPTED WITH BYPASS SURGERY OR BY INFLATING A SMALL BALLOON IN THE ARTERY. THE MAIN VESSEL, THE MAIN STREET IS TOTALLY BLOCKED. Alda: BUT FOR LILLIAN, THESE HAVE ALREADY FAILED. YOU'VE HEARD ABOUT GENE THERAPY... YES, I HAVE. AND IN THIS CASE WHAT WE ARE GOING TO DO IS USE GENE THERAPY TO TRY TO MAKE NEW BLOOD VESSELS GROW FROM THIS ARTERY THAT'S RIGHT ABOUT IN THE MIDDLE PART OF YOUR LEG. Alda: GENE THERAPY HAS BEEN HIGHLY TOUTED AS THE FUTURE OF MEDICINE. A HUGE RESEARCH PROJECT TO LOCATE AND READ ALL THE 100,000 OR SO HUMAN GENES IS NOW IN FULL SWING. IT'S ANOTHER DRAMATIC EXAMPLE OF HOW INFORMATION-- IN THIS CASE THE SPELLING OF THE OPERATING INSTRUCTIONS FOR THE HUMAN BODY-- IS TRANSFORMING MEDICINE. AND IT'S LED TO THE HOPE THAT HUMAN GENES CAN THEMSELVES BE USED TO TREAT PEOPLE. ONE OF THESE GENES MANUFACTURES A CHEMICAL THAT CAN MAKE BLOOD VESSELS GROW. JEFFREY ISNER'S IDEA IS TO SEE IF PUTTING THIS GENE INTO BLOCKED ARTERIES WILL CAUSE THEM TO DEVELOP SHOOTS THAT WILL BYPASS THE BLOCKAGE. Isner: THE IDEA THAT PEOPLE COULD GROW THEIR OWN BYPASS IS AN INTRIGUING ONE BECAUSE THERE IS NOTHING LIKE LETTING NATURE DO THE SURGERY. Alda: TO DELIVER THE GENE, ISNER EMPLOYS A NARROW BALLOON THAT CAN BE SLID INTO LILLIAN'S ARTERY TO A POINT JUST ABOVE THE BLOCKAGE AND INFLATED TO SQUASH THE GENE INTO THE BLOOD VESSEL'S WALLS. HUNDREDS OF MILLIONS OF COPIES OF THE GENE ARE COATED ONTO THE BALLOON AND THEN DRIED SO THAT THEY STICK THERE. Isner: IT SEEMS LIKE A LOT BUT WE KNOW THAT NOT ALL OF THE DNA IS GOING TO COME OFF OF THE BALLOON AND ONTO THE WALL OR INTO THE WALL OF THE ARTERY. AND EVEN ALL THAT GETS INTO THE WALL OF THE ARTERY WILL NOT NECESSARILY FIND ITS WAY INTO THE CELLS-- THE SMOOTH MUSCLE CELLS-- OF THE ARTERIAL WALL. AND EVEN THE AMOUNT THAT GETS INTO THE CELLS WILL NOT ALL BECOME OPERATIVE IN TERMS OF MAKING THE GROWTH FACTOR. Alda: EVERYTHING IS READY FOR THE GENES TO BE DELIVERED. ALL RIGHT, READY? HERE WE GO. Alda: A PUMP INFLATES THE BALLOON. NOW ALL EVERYBODY CAN DO IS WAIT AND SEE IF THE GENES GOT IN, IF THEY WORK IF NEW BLOOD VESSELS BYPASS LILLIAN'S BLOCKAGE. Cooper: MY IMMEDIATE DREAM IS TO GO BACK TO THE MALL-WALKERS AND BE ABLE TO WALK RIGHT IN. AND I'M SURE THEY'RE ALL GOING TO BE THERE HOPING FOR THE SAME THING. THAT MEANS I'LL START MY LIFE AGAIN DOING THE THINGS THAT I'VE ALWAYS WANTED TO DO. Alda: IF THE GENE THERAPY GROWS A BYPASS FOR LILLIAN'S BLOCKED LEG ARTERY IT HAS IMPLICATIONS FOR OTHER PLACES BYPASSES ARE NEEDED-- MOST OBVIOUSLY, THE HEART. JEFFREY ISNER'S ULTIMATE GOAL IS TO USE GENE THERAPY AS AN ALTERNATIVE TO BYPASS SURGERY IN PEOPLE WITH CORONARY ARTERY DISEASE. IT'S BEEN FOUR WEEKS SINCE LILLIAN'S TREATMENT. Cooper: YESTERDAY I WALKED FROM THE HOSPITAL DOWN THE MAIN STREET OVER A HALF A MILE, AND I KEPT GOING. I FEEL THAT THERE HAVE TO BE NEW BLOOD VESSELS FORMING BECAUSE WHAT ELSE WOULD CAUSE THIS? MY LEG IS BETTER, MY FOOT IS BETTER, I CAN WALK BETTER. HAS TO BE THAT. WE'LL HAVE TO USE THAT CANE AS KINDLING. ( laughing ) Alda: TO FIND OUT IF MORE BLOOD IS FLOWING TO LILLIAN'S LEG SHE HAS YET ANOTHER ANGIOGRAM. THE RESULT AT LEAST PARTIALLY JUSTIFIES HER OPTIMISM. WHILE BEFORE IT TOOK 15 SECONDS FOR BLOOD TO REACH HER CALF NOW IT TAKES ONLY NINE. Isner: WE'RE NOT SEEING TUFTS OF NEW VESSELS AND WE'RE NOT SEEING SPLASHES OF ARTERIES THAT WE NEVER SAW BEFORE. IT'S POSSIBLE THAT THE NEW ARTERIES THAT ARE DEVELOPING ARE OF A SIZE THAT THEY'RE JUST A LITTLE BIT TOO SMALL FOR US TO SEE ON THESE ANGIOGRAMS UM... BUT YET, THERE ARE STILL ENOUGH OF THEM AND THEY'RE STILL FUNCTIONAL ENOUGH THAT THEY'RE PRODUCING, YOU KNOW, NEW CONDUITS NEW AVENUES FOR BLOOD FLOW TO THE LOWER LEG. Alda: GENE THERAPY IS STILL IN ITS INFANCY AND SO FAR, MOST OF THE 100 OR MORE CLINICAL TRIALS USING GENES HAVE BEEN DISAPPOINTING OR INCONCLUSIVE. BUT THIS ONE JUST MIGHT BE DIFFERENT. Isner: WHENEVER YOU TRY SOMETHING LIKE THIS FOR THE FIRST TIME, YOU ALWAYS WONDER, IS IT SCIENCE FICTION OR IS IT GOING TO BE REAL THERAPY? UM... A LOT OF THINGS WE TRY TURN OUT TO BE SCIENCE FICTION-- MAKE GOOD MOVIES, BUT THEY DON'T HELP TOO MANY PATIENTS. I THINK THIS HAS THE POTENTIAL TO BE GREAT SCIENCE FICTION BUT NOW WE'RE SEEING A FEW INDICATORS THAT SUGGEST THAT IT ACTUALLY MIGHT BE USEFUL MIGHT ACTUALLY BE THERAPEUTIC FOR CERTAIN GROUPS OF PATIENTS. HOW MANY MILES DO YOU USUALLY WALK IN A DAY? I WALK A MILE AND A HALF EVERY DAY. THAT'S VERY GOOD, YEAH. Alda: SIX MONTHS AFTER LILLIAN'S GENE THERAPY AND SHE'S BACK AT THE MALL. Cooper: IT FEELS WONDERFUL TO BE WALKING AGAIN. THERE WERE TIMES WHEN I THOUGHT WALKING A FEW STEPS WITH A CANE WOULD BE ABOUT IT. BUT NOW I CAN WALK AROUND THE MALL, MOSTLY WITHOUT STOPPING. SO, I'M REALLY THRILLED WITH THE WAY EVERYTHING HAS TURNED OUT. AND I'M HOPING THAT IT WILL GET BETTER ALL THE TIME AND I'M SURE IT WILL. ... KNOW WHICH ONES TO COME BACK TO. ( laughing ) SAVE A LOT OF MONEY SHOPPING THIS HOUR. Alda: THERE WAS ONCE A TELEVISION SERIES SET IN A MOBILE ARMY SURGICAL HOSPITAL

				Evolving Beaks Darwin’s famous finches exemplify evolution in action, as each generation's average beak size correlates to seed size on the island of Daphne Major.
		Select text to jump ahead in the clip: " AND THIS GOES DOWN, RIGHT? Anderson: YEP. Alda: WE'RE SETTING UP A MIST NET TO CATCH ONE OF THE GROUP OF BIRDS THAT HAS BECOME LITERALLY SYNONYMOUS WITH DARWIN AND HIS THEORY OF EVOLUTION. THIS NEEDS TO BE LOOSE LIKE THIS? YEAH, WHAT HAPPENS IS THE BIRD FLIES IN AND DOESN'T SEE IT AND SO IT CARRIES THE NET OUT WITH IT WITH ITS MOMENTUM AND THEN SAGS DOWN, HANGING LIKE THIS IN A LITTLE BAG. Both: PSSH, PSSH, PSSH. CAN THEY HEAR THAT? YOU CAN ALSO GO LIKE THIS-- ( making squeaking noise ) DO YOU DO THAT WHEN YOU'VE BEEN HERE TOO LONG? BIRDERS ACT LIKE THEY KNOW WHAT THEY'RE DOING AND THEY MAKE THESE LITTLE SQUEAKY SOUNDS AND THEY ALL PRETEND LIKE IT MAKES A DIFFERENCE. I DON'T KNOW WHETHER IT DOES OR NOT. Both: PSSH, PSSH, PSSH. YOU GOT ONE, YOU GOT ONE! IT'S A SHARP-BEAKED GROUND FINCH. Alda: OUR BIZARRE CALLS HAVE NETTED US A BIRD FROM ONE OF THE 13 DIFFERENT SPECIES OF FINCHES IN THE GALAPAGOS-- BIRDS THAT ARE TODAY KNOWN COLLECTIVELY AS "DARWIN'S FINCHES. " NOW, WHAT IS THIS AGAIN? THIS IS THE SHARP-BEAKED GROUND FINCH. THIS IS THE SMALLEST GROUND FINCH ON THIS ISLAND. IT'S GOT A POINTY LITTLE BEAK THAT'S GREAT FOR GRASS SEEDS. Alda TODAY DARWIN'S FINCHES ARE IN ALL THE TEXTBOOKS AS THE CLASSIC EXAMPLE OF HOW LIVING THINGS ADAPT TO THEIR ENVIRONMENT. EACH OF THE 13 SPECIES IN THE GALAPAGOS HAS A DIFFERENT BEAK THAT SUITS ITS LIFESTYLE-- FROM FEEDING OFF CACTUS FLOWERS TO USING TWIGS TO DIG OUT INSECTS FROM THE BARK OF TREES. A GROUP OF SPECIES KNOWN AS GROUND FINCHES ARE THE MOST COMMON. THIS IS THE LARGE GROUND FINCH, WITH A THICK, HEAVY BEAK PERFECT FOR CRACKING OPEN LARGE TOUGH SEEDS. THE SHARP-BEAKED GROUND FINCH BY CONTRAST EATS MAINLY SMALL SEEDS. Anderson: IF YOU GAVE THIS GUY A GRAM OF SMALL SEEDS TO EAT IT WOULD GET DONE A LOT FASTER THAN WITH THIS GUY. Alda: BECAUSE HE'S GOT TOO MUCH BEAK IN THE WAY? HE'S GOT TOO MUCH EQUIPMENT THERE, YEAH. IT'S TOO BIG, IT'S TOO BULKY. HE CAN HANDLE IT BUT NOT FAST ENOUGH. YEAH, SO HE'D HAVE TO SPEND MORE ENERGY ON FEEDING HIMSELF THAN HE NEEDS THE ENERGY TO DO IT. YEAH, HIS NET INTAKE WOULD PROBABLY BE NEGATIVE. WOW, SO HE COULD... ALTHOUGH HE'S PROBABLY EATING ALL DAY LONG HE COULD EVENTUALLY STARVE TO DEATH. YEAH, HE'S GOT EXPENSES. HE'S GOT OVERHEAD HE'S GOT TO PAY. YEAH, RIGHT, TOO MUCH OVERHEAD. AND YOU LOOK AT THE BODY SIZES AND HE'S GOT A LOT MORE OVERHEAD THAN THIS ONE. Alda: CONTRARY TO LEGEND DARWIN HIMSELF DIDN'T PAY MUCH ATTENTION TO THE DULL LITTLE BIRDS THAT OFTEN HOPPED AROUND HIS FEET. HE COLLECTED SEVERAL DOZEN WHILE HE WAS HERE BUT HE DIDN'T EVEN BOTHER TO LABEL THEM OR NOTE WHICH ISLAND THEY CAME FROM. BUT BY A DELICIOUS TWIST OF FATE IT'S THE FINCHES ON ONE OF THE GALAPAGOS ISLANDS-- AN ISLAND DARWIN DIDN'T EVEN VISIT-- THAT HAVE BECOME THE SINGLE BEST PROOF THAT HIS THEORY OF EVOLUTION IS NO LONGER ONLY A THEORY BUT AN OBSERVABLE FACT. YEP, YEP. Alda: AS WE APPROACH THE ISLAND I CAN SEE WHY DARWIN NEVER LANDED HERE. YOU MEAN, ON THE FACE OF THAT CLIFF. RIGHT THERE, YEP. IT LOOKS A LITTLE WORSE FROM HERE THAN IT REALLY IS. MAYBE NOT. IT'S NOT ONLY A CLIFF. THE CLIFF STICKS OUT AT THE TOP. Alda: THE ISLAND, CALLED DAPHNE MAJOR, IS ONLY A MILE OR SO ACROSS. FOR SOME QUARTER CENTURY NOW A TEAM OF BIOLOGISTS AND A STRING OF GRADUATE STUDENTS INCLUDING BRIEFLY DAVE ANDERSON HAVE BEEN COMING HERE EVERY YEAR. ALL RIGHT! THIS GUY'S LIKE A SPIDER. Alda: THE RESEARCHERS' SINGLE PURPOSE HAS BEEN TO WEIGH AND MEASURE EVERY ONE OF THE FEW HUNDRED GROUND FINCHES THAT SHARE THIS LUMP OF VOLCANIC ROCK WITH LOW, RATHER SCRUBBY VEGETATION, SOME SEABIRDS AND NOT MUCH ELSE APART FROM THE OCCASIONAL GRUMPY SEA LION. ( barking ) OKAY, I'M SORRY, I'M SORRY. JUST PASSING THROUGH. WHY DO PEOPLE GO TO ALL THIS TROUBLE OF GETTING ON THIS THING? WHAT'S THE SIGNIFICANCE TO SCIENCE OF DAPHNE MAJOR? WELL, THERE ARE SOME FOLKS WHO CALL DAPHNE MAJOR THE LABORATORY OF EVOLUTION. IT'S A REALLY GREAT PLACE TO SEE EVOLUTION ACTUALLY HAPPENING BECAUSE THE SYSTEM, THE BIOLOGICAL SYSTEM, IS RELATIVELY SIMPLE: NOT TOO MANY COMPONENTS AND FOR THE FINCHES IT KIND OF BOILS DOWN TO WHAT SEEDS ARE HERE AND "WHAT TOOL DO I HAVE TO CRACK THOSE SEEDS? " Alda: THE MAIN GROUND FINCH HERE IS ABOUT HALFWAY IN SIZE BETWEEN THE TWO SPECIES DAVE AND I LOOKED AT EARLIER. WHAT THE RESEARCHERS HAVE FOUND IS THAT WHEN SMALL SEEDS ARE PLENTIFUL USUALLY IN RAINY YEARS THE BEAKS OF THE BIRDS BORN THE FOLLOWING YEAR ARE ALSO, ON AVERAGE, SMALLER. WHEN THERE ARE PLENTY OF LARGE SEEDS, IN DRIER YEARS THE NEXT GENERATION HAS BEAKS THAT ARE LARGER. WHEN SMALL SEEDS ARE PLENTIFUL, WHEN THERE'S BEEN PLENTY OF RAIN THE SMALLER-BEAKED BIRDS ARE THE MORE-EFFICIENT EATERS SO THEY THRIVE AND PRODUCE MORE OFFSPRING THAN THE LARGER-BEAKED BIRDS. THE RESULT IS THAT IN THE NEXT GENERATION THERE ARE MORE SMALL- THAN LARGE-BEAKED BIRDS. THE AVERAGE BEAK SIZE IS SMALLER THAN THE LAST GENERATION. THE POPULATION HAS EVOLVED. WHEN CONDITIONS CHANGE AND A DRY YEAR BRINGS MORE LARGE SEEDS THAN SMALL THEN LARGE-BEAKED BIRDS DO BETTER. THEY LEAVE MORE OFFSPRING AND THE POPULATION SHIFTS TOWARD A LARGER AVERAGE BEAK SIZE. SMALLER TO LARGER, LARGER TO SMALLER-- IT'S THESE SUBTLE SHIFTS IN BEAK SIZE THAT THE RESEARCHERS HAVE SO METICULOUSLY DOCUMENTED. Anderson: THE REALLY SIGNIFICANT THING THEY FOUND IS THAT OSCILLATING BACK AND FORTH THAT THE SIZE OF THE BEAK REALLY DOES CHANGE OVER SHORT PERIODS OF TIME, AND THEY KNOW EXACTLY WHY. IT'S BECAUSE THEIR FOOD SUPPLY CHANGES. AND THAT'S A CASE OF ACTUALLY SEEING EVOLUTION IN PROGRESS TO SEE IT AS IT HAPPENS? YEAH, YEAH, THE REALLY COOL THING ABOUT THIS FOR EVERYBODY, SCIENTISTS AND EVERYBODY ELSE IS THAT THERE'S NO QUESTION THAT IT IS EVOLUTION HAPPENING IN FRONT OF OUR EYES. WE DON'T HAVE TO THINK OF EVOLUTION AS BEING SOMETHING THAT YOU ONLY GET FROM THE FOSSIL RECORD OR THEORIZING ABOUT IT. YOU CAN GO TO A PLACE LIKE DAPHNE MAJOR, WHERE IT'S SIMPLE AND YOU CAN ACTUALLY SEE EVOLUTION HAPPENING ALMOST ON A MONTHLY BASIS, BUT CERTAINLY AN ANNUAL BASIS. I'VE OFTEN HEARD PEOPLE SAY-- PEOPLE SYMPATHETIC TO THE IDEA OF EVOLUTION-- THAT YOU HAVE TO TAKE A LITTLE BIT OF IT ON FAITH. BUT YOU DON'T HAVE TO TAKE ANY OF IT ON FAITH? NOT ANYMORE. NOT ANYMORE, NOT AFTER THIS STUDY. PEOPLE VISIT HERE, NOT JUST SCIENTISTS. THEY NEED A TRAIL THAT'S ESTABLISHED. Alda: IT'S WONDERFULLY APPROPRIATE THAT EVOLUTION SHOULD MOVE FROM THEORY TO FACT IN A STUDY ODARWIN'S FINCHES BECAUSE IT WAS WHILE DARWIN HIMSELF WAS TRYING TO MAKE SENSE OF HIS HAPHAZARD FINCH COLLECTION THAT THE IDEA OF EVOLUTION FIRST OCCURRED TO HIM. WITH IT, HE COULD EXPLAIN NOT ONLY WHY DIFFERENT ISLANDS HAVE DIFFERENT FINCHES BUT ALSO DIFFERENT MOCKINGBIRDS... DIFFERENT PLANTS... DIFFERENT TORTOISES. FROM THE TIME THEIR ANCESTORS ARRIVED IN THE ARCHIPELAGO THE ANIMALS ON DIFFERENT ISLANDS HAVE GONE THEIR OWN INDEPENDENT WAYS SHAPED BY THE CONDITIONS THEY FOUND THEMSELVES IN UNTIL EVENTUALLY THEY BECAME DIFFERENT SPECIES. AS FOR HOW THEIR ANCESTORS GOT HERE WELL, WE'RE COMING TO THAT. GETTING HERE WAS NO PROBLEM