The DNA Files:
Unraveling the Mysteries of Genetics

As heard on National Public Radio

The Heat is On: Evolution in Action

Hosted by John Hockenberry

Transcript

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JOHN HOCKENBERRY: This is The DNA Files. I'm John Hockenberry. By now, everyone's heard about climate change, but we tend to think that the ecological effects of a warming world are mostly down the road.

PAUL EHRLICH: It's already happening. Plants and animals and micro-organisms are changing their distributions and behavior in response to climate change.

JOHN HOCKENBERRY: Perhaps even more surprising, species have already started to evolve.

WILLIAM BRADSHAW: We think evolutionary time takes decades or centuries or a millennia to occur, and we don't think of evolutionary time being on the order of a few years, and when we saw the shift over a five year period, that said to us, "This is evolution occurring at a breakneck speed due to climate warming."

JOHN HOCKENBERRY: On today's edition of The DNA Files, "The Heat is On: Evolution in Action," coming up after the news.
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JOHN HOCKENBERRY: Welcome to The DNA Files. I'm John Hockenberry. Today's program is about climate as an evolutionary force. We know that the planetary and the genetic are connected. The big trends on earth have, since the beginning of life, shuffled the genes, and shaped the evolution of life on earth. But making real connections between the two, that--that's tricky. I mean, it's a long distance from the planetary to the genetic.

ADAM BURKE: Don't forget to tell them we're orbiting in our spaceship, John.

JOHN HOCKENBERRY: Oh, I was just getting to the spaceship. Folks, meet Adam Burke. He's our program's producer, reporter. He's a mechanic, right? Think of him as the person who keeps our scientific metaphors in tiptop shape. Now, he's currently repairing a few mechanical things before we get underway in our spaceship. How's it going, Adam?

ADAM BURKE: Fine. Almost done.

JOHN HOCKENBERRY: As I was saying, it's a long way between the planetary and the genetic, but scientists are making some connections.

ADAM BURKE: Okay, all fixed up and ready to go.

JOHN HOCKENBERRY: Yeah, right. We've got a program to do here. Okay. So imagine you're above planet earth as we are right now in our spaceship. Man, that is one nice place to look at, Earth.

ADAM BURKE: Not a bad view at all.

JOHN HOCKENBERRY: Not a bad view at all? It's earth, for heaven's sakes, and if you stayed up here a long time, you'd start to see things. That's right. You'd see changes in response to a warming world. The glaciers at the poles are changing, as many have heard, but when we talked to Camille Parmesan--she's a biologist at the University of Texas--she told us that some of the biological changes underway right now would also be visible over time.

CAMILLE PARMESAN: From space, what you'd be seeing is sort of an expansion of the Tropics, tropical species moving into temperate zones, temperate zone species moving into boreal zones, the boreal forest moving into the tundra, and then the polar regions getting much smaller.

JOHN HOCKENBERRY: We tend to think that it's just a few exotic and polar species that have already started reacting to climate change. After all, the earth has only warmed .7 degrees Centigrade on average over the past century.

ADAM BURKE: That would be 1.2 degrees Fahrenheit, John.

JOHN HOCKENBERRY: Thank you, Adam. A few years ago, Camille Parmesan and a colleague looked into just how many species had responded in some way to climate change. They compiled data on more than 1,700 species worldwide--everything from plants to birds to butterflies to inter-tidal invertebrates to plankton. Across all of these groups, half of the species are showing some kind of a response.

CAMILLE PARMESAN: Either they're breeding earlier or they're shifting the ranges northward, or they're accelerating their generation time. So you know, it's a little different, depending on who you're looking at, but that's absolutely astounding, that 50% of species are doing something different from what they were doing 30 or 40 or 100 years ago.

JOHN HOCKENBERRY: Parmesan says that about 40% of the species she's looked at have shifted their ranges away from the equator and toward the poles.

CAMILLE PARMESAN: And this is a combination of shifting their breeding grounds, if they're a migratory species, or actually shifting where they live. So if they're a very sedentary species that doesn't move very much, they're actually shifting the whole region in which they live.

JOHN HOCKENBERRY: So this is one strategy for dealing with climate change. Species are moving to follow their climate. Not necessarily a new strategy, though.

CAMILLE PARMESAN: During the glacial and interglacial cycles, the Pleistocene glaciations, species would move around by 1,000, 2,000 miles, trying to track their climate.

JOHN HOCKENBERRY: Of course, back then, creatures didn't have an obstacle course of freeways, farm fields, and cities to deal with when they moved. So this time around, some are managing and some aren't, but it definitely seems to be a popular coping strategy. Are there any others, Adam?

ADAM BURKE: Well, there's timing. Parmesan told us that species are also shifting when they do things, too. So take spring, for example.

JOHN HOCKENBERRY: I love spring.

CAMILLE PARMESAN: So we're seeing birds breeding earlier, frogs breeding earlier, trees leafing out earlier, flowers blooming earlier.

ADAM BURKE: And you know, there's a growing body of science that says at least some of these shifts are genetic.

JOHN HOCKENBERRY: Really?

ADAM BURKE: Yup. Ooh, speaking of timing, pardon me.

JOHN HOCKENBERRY: What are you doing?

ADAM BURKE: Seatbelt.

JOHN HOCKENBERRY: Whoa.

ADAM BURKE: Okay, hold on.

JOHN HOCKENBERRY: Hold on? Hey. Does that mean we're going in?

ADAM BURKE: Oh, yeah, we're going in and out into the living room of two scientists in Eugene, Oregon.

JOHN HOCKENBERRY: Whoa. [laughs] Warn me about that next time, will you?

ADAM BURKE: Yeah, like I'm going to warn you. It's way more fun not to warn you. Now, listen, these scientists study an insect called the pitcher plant mosquito. The scientific name: Wyeomyia smithii, although William Bradshaw refers to it affectionately as Wyeomyia.

WILLIAM BRADSHAW: Wyeomyia is a mosquito that breeds only in the stomach of a carnivorous plant.

ADAM BURKE: That plant grows in bogs all the way from the Gulf of Mexico to Northern Canada.

JOHN HOCKENBERRY: Whoa.

ADAM BURKE: Yeah, and its leaves are shaped like a small water pitcher.

JOHN HOCKENBERRY: No.

ADAM BURKE: Really.

CHRISTINA HOLZAPFEL: This is a pitcher plant that collects rainwater throughout the year.

ADAM BURKE: And that's Christina Holzapfel. She and her husband, William Bradshaw, are evolutionary biologists, and they have been studying the pitcher plant mosquito for over 35 years. So they're fairly well acquainted with the host plant and the mosquito larva, which is a teeny --

CHRISTINA HOLZAPFEL: Teeny, tiny, little --

ADAM BURKE: Little wrigglers they're called. Now, these wrigglers live in the watery bowl of the plant, feeding on a buffet of mucky rainwater and disintegrating insects that are trapped there.

JOHN HOCKENBERRY: Delicious.

CHRISTINA HOLZAPFEL: They have little orange mouth brushes, and those little brushes are filtering the food that they eat.

ADAM BURKE: So that's what these little wrigglers do. All summer long, eggs hatch in the plants, and juveniles wriggle around, eating and growing, and eventually becoming adults. It takes between three to four weeks on average, but around late summer, early fall, these larva come to a fork in the road.

JOHN HOCKENBERRY: That's right. They have to go back to mosquito school, right? I mean, they have to buy their lunch boxes. They have to get their fashions--new shoes, right?

ADAM BURKE: No, John. Adult pitcher plant mosquitoes can't make it through the winter. So after a certain point in the year it’s no longer safe to turn into an adult. Around late summer or early fall, the larva shift into a sort of holding pattern called dormancy. So they won't develop into adults until spring.

JOHN HOCKENBERRY: Wow, so--so, they turn into like Peter Pan mosquitoes all winter long, just stuck in childhood, eating and wriggling around in the belly of the plant?

ADAM BURKE: Yeah. Even under the snow.

JOHN HOCKENBERRY: Whoa. But wait a minute, didn't you say that the larva start to go into dormancy around August or September?

ADAM BURKE: That's right.

JOHN HOCKENBERRY: But how do they know winter is coming? I mean, fall hasn't even arrived yet.

ADAM BURKE: Ah, that's where the plot thickens, John. They use the length of day.

WILLIAM BRADSHAW: When days are getting short, winter is coming. When days are getting long, spring is coming, and Wyeomyia has a highly accurate ability to measure the length of day. They can measure the length of day to within five minutes, and they use day length then to predict into the future when winter is coming, and to time the onset of their dormancy at the optimal time.

JOHN HOCKENBERRY: These Wyeomyias can measure the length of day to within five minutes?

ADAM BURKE: Yup. Birds use similar cues to determine when to migrate.

JOHN HOCKENBERRY: Really?

ADAM BURKE: Yeah, they're not conscious decisions. They're genetic cues, hardwired into the animal.

JOHN HOCKENBERRY: So little clocks hardwired into mosquitoes and birds, what does any of this have to do with climate change?

ADAM BURKE: Well, when Bradshaw and Holzapfel started their research in the early 1970s, they didn't know it had anything to do with climate change. They were just studying the timing of when pitcher plant mosquitoes were entering dormancy. But in Spring of 2002, they suddenly realized their mosquito work might have something to say about climate change and evolution. They analyzed data comparing the timing of dormancy over a 24-year period, then, a bit shocked, they checked a five-year comparison.

CHRISTINA HOLZAPFEL: What we expected to see in the analysis of the five-year data set was nothing. What we actually saw was that the mosquitoes were evolving in a tiny, short time frame--five years. That was just stunning to us.

WILLIAM BRADSHAW: We talk about evolutionary time, and we think evolutionary time takes decades or centuries or a millennia to occur, and we don't think of evolutionary time being on the order of a few years, and when we saw the shift over a five year period, that said to us, "This is evolution occurring at breakneck speed due to climate warming."

JOHN HOCKENBERRY: So wait a minute, wait a minute. Evolution at breakneck speed. What does that mean?

ADAM BURKE: That means that populations of pitcher plant mosquitoes are evolving to shift the timing of their dormancy to later in the year. The timing of dormancy and the pitcher plant mosquito is genetic, remember?

JOHN HOCKENBERRY: Okay, right, right.

ADAM BURKE: Okay, good. So here's how it works. Each population of mosquitoes has evolved to go into dormancy at a particular time of the year.

JOHN HOCKENBERRY: Okay.

ADAM BURKE: But within any one population, there will be a range of responses.

JOHN HOCKENBERRY: Well, of course.

ADAM BURKE: Some individual larva will go into dormancy earlier, some go later.

JOHN HOCKENBERRY: Okay. I think I'm still with you.

ADAM BURKE: The thing is, there are evolutionary consequences to the timing of all of this.

WILLIAM BRADSHAW: Timing is essential.

CHRISTINA HOLZAPFEL: Dormancy is all about timing. If you go into dormancy very, very early into the season, you haven't had an adequate opportunity to make lots of progeny or young.

WILLIAM BRADSHAW: If you go dormant too late, you die.

CHRISTINA HOLZAPFEL: And that's a bad thing as well.

ADAM BURKE: So this is something Bradshaw and Holzapfel call "strong selection pressure."

JOHN HOCKENBERRY: [laughs] Meaning there are rewards for getting the timing right. You get to live.

ADAM BURKE: And negative consequences to getting the timing wrong. Now, here is what's interesting about all of this. The factors that determine what's too late and what's too early for the mosquito are shifting with climate change.

JOHN HOCKENBERRY: Okay.

ADAM BURKE: What happens when you go into dormancy too late?

JOHN HOCKENBERRY: You die.

WILLIAM BRADSHAW: You die.

ADAM BURKE: With climate change, winters are milder than they used to be. So the cut-off point separating the mosquitoes that die from the ones that live is actually arriving later in the year, or another way to look at it, mosquito populations in the far north go into dormancy around a week later than they did 30 years ago.

JOHN HOCKENBERRY: It sounds like that there's some sort of optimal window in time, and that that window is shifting later in the year.

ADAM BURKE: Well, it's thanks in part to that variation, right? By having a range of timing responses within a population, the pitcher plant mosquito always has a chunk of individuals that get the timing right.

JOHN HOCKENBERRY: Aha.

ADAM BURKE: And make it through the window to pass on their genes.

JOHN HOCKENBERRY: And because they have short generation times, the mosquito can evolve in a time period as short as five years, right?

ADAM BURKE: Exactly, though it's kind of a bittersweet thing for Bradshaw and Holzapfel.

CHRISTINA HOLZAPFEL: We feel the fact that Wyeomyia is able to adapt and evolutionarily change in response to rapid climate change is a very positive thing. It makes us feel happy. At the same time, we are not so naive to think that we can take its success, and say that that reflects what is going to happen to large mammals and to humans, for example.

ADAM BURKE: If you think about it, a mosquito can go through many generations in the time it takes a polar bear to learn its first baby steps.

JOHN HOCKENBERRY: Yikes. So that means many species aren't going to be able to bob and weave here. I mean, they're not going to be able to adapt, especially in the hardest hit areas of the globe. We've heard about the poles, but there's another red zone. Coming up after the break, the heat is on in Australia. You're listening to The DNA Files. We'll be back in a minute.
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JOHN HOCKENBERRY: Welcome back to The DNA Files. I'm John Hockenberry, here with reporter Adam Burke. Adam?

ADAM BURKE: Hi, again.

JOHN HOCKENBERRY: We're exploring climate change as an evolutionary phenomenon, a force that's re-jiggering the planet on both a physical level and a genetic level, and we've sent our producer, Adam, out into the world, out into the world--did you hear that Adam?--to find out how global warming is pushing species around. Before the break, we heard how species are shifting around geographically, changing their seasonal timing, and adapting genetically in response to a warming world.

ADAM BURKE: But if, on the other hand, you don't have that kind of wiggle room --

JOHN HOCKENBERRY: For example, if you happen to be a little colony of branching coral on Australia's Great Barrier Reef --

ADAM BURKE: And we're not saying that you are.

JOHN HOCKENBERRY: But let's just say for the sake of argument, that you are a small reddish brown colony of coral, about the size of a head of cauliflower attached to a lumpy stretch of reef. It's not like you can pack up the store and head south or north or wherever things might be better. You're stuck. You just sit there.

It sounds like we're on a boat. What happened? Are we on a boat?

ADAM BURKE: We are on a boat, near the Lizard Island Research Station, which is at the northern end of the Great Barrier Reef.

JOHN HOCKENBERRY: Okay.

ADAM BURKE: And a team of divers from James Cook University are getting ready to collect the kind of coral you were just talking about.

JOHN HOCKENBERRY: You mean, the small, reddish brown, about the size of a head of a cauliflower coral?

ADAM BURKE: Yeah, that one. Pocillopora Damicornis, the kind marine biologist Morgan Pratchett studies.

MORGAN PRATCHETT: It's one of the more important corals in terms of habitat for fish and other invertebrates, which tend to live in the branches of corals. So we're going to go collect a heap of these corals, and see what's inside them.

JOHN HOCKENBERRY: Inside of coral? What's inside of coral?

ADAM BURKE: Well, he's looking for little crabs and shrimp and starfish and other critters that live in the nooks and crannies of the branches.

JOHN HOCKENBERRY: Aha.

ADAM BURKE: So soon they're swimming around 15 feet below the surface, prying loose colonies of Pocillopora Damicornis. That's just one of over 300 species of coral in the Great Barrier Reef. They come in all sizes, shapes, and colors.

MORGAN PRATCHETT: Typically, that ranges from brown to green to blue and really quite dark colors.

ADAM BURKE: Some look like big thickets of branching antlers. Others are round and solid, textured like brains. But the structure you see is not the coral animal. It's a calcified skeleton of sorts.

JOHN HOCKENBERRY: It's like the house of the animal, I guess, right?

ADAM BURKE: More like a high-rise building, and the tiny coral animal is attached to the calcified structure. And living inside the cell tissue of this coral animal are microscopic single-celled plant species called--brace yourself for this, John--zooxanthellae.

JOHN HOCKENBERRY: Zooxanthellae. [laughs] Hey, how do you like me now? That is a mouthful, though.

ADAM BURKE: Yeah, and it's this symbiosis that allows corals to grow all these fancy structures. The photosynthetic plant harnesses energy from the sun and passes on nutrients to the coral animal, and the coral animal gives nutrients to the plant.

JOHN HOCKENBERRY: So this animal and plant working together, build all these fabulous [laughs] apartment buildings. Is it a happy relationship?

ADAM BURKE: It's a happy relationship most of the time. But it falls apart when times get tough--pollution, changes in ocean salinity, temperature extremes.

MORGAN PRATCHETT: Any number of these factors could cause the coral to become physiologically stressed, and as a consequence, it will undergo a bleaching. And bleaching is a process where the symbiotic algae, the zooxanthellae, essentially are evicted from the coral host.

JOHN HOCKENBERRY: This bleaching business sounds serious I mean, can the coral roommates get back together?

ADAM BURKE: Well, that depends on how extreme the stress factors are. Historically, bleaching events were small and local, but over the last few decades, warmer ocean temperatures have brought regional scale bleaching. In 1998, it's estimated that 12 to 15% of the world's corals died. So with global temperatures going up, Morgan Pratchett is trying to understand the relationship between reef biodiversity and the presence of living coral.

MORGAN PRATCHETT: We don't know all the myriad of organisms which live on a reef, but if we just think about coral reef fish, at least 70% of those species decline in abundance after a bleaching event.

ADAM BURKE: And don't forget, it's the fish that bring in all of those snorkeling tourists --

JOHN HOCKENBERRY: Right.

ADAM BURKE: Worth about five billion Australian dollars a year.

JOHN HOCKENBERRY: Whoa. That's how the food chain works, I guess. It's not just a few scientists who are wringing their hands over climate change in coral reefs, eh?

ADAM BURKE: No.

JOHN HOCKENBERRY: So it seems that the key question here is: Can coral actually adapt to warmer oceans, even though it's stuck right where it is?

ADAM BURKE: Well, some scientists say no.

JOHN HOCKENBERRY: Oh.

ADAM BURKE: And the reason is that symbiosis we were talking about earlier.

JOHN HOCKENBERRY: You mean the zooxanthellae business with the little coral animal you were talking about?

ADAM BURKE: Yeah, it's a tricky evolutionary relationship. I mean, let's say, one of these symbiotic zooxanthellae is floating around in the ocean.

JOHN HOCKENBERRY: Okay.

ADAM BURKE: Just a little cell, and then that little cell bumps into the particular species of coral host that it likes to live with.

JOHN HOCKENBERRY: Okay.

ADAM BURKE: That symbiont has to get inside a cell of the coral animal, which is not the easiest thing to do.

OVE HOEGH-GULDBERG: Cells spend a lot of energy trying to prevent things from invading them, because they're a little lump of energy, and they're trying to keep it for themselves, right?

JOHN HOCKENBERRY: Meet Ove Hoegh-Guldberg, a marine biologist at the University of Queensland.

OVE HOEGH-GULDBERG: These are these immune systems, and there's ways of destroying invading pathogens and bacteria and so on, and then suddenly it's, "Come inside. Live inside my cell. You know, I'm not going to fear you. I'm going to live with you." And, of course, that's a very bizarre situation, when you think about it.

JOHN HOCKENBERRY: I'll say. But they are coral, after all. And how do these coral know if you're a friendly cell or an enemy cell?

OVE HOEGH-GULDBERG: What we do know is that there are some molecules in the surface of the right type of zooxanthellae, which are being recognized by systems on the coral side. This is acting essentially like a set of keys. You get the key to the first room, if you get into the cell. A broad range of cells might actually get taken in. What happens next is if they're the wrong type, then they get attacked by little parts of the host cell called lysosomes, and they're eliminated that way. So if you have the first set of keys, you get into that first room. If you have the second set of keys, you avoid digestion.

Then the next trick is, of course, you've now got to integrate into the physiology of the host. So this is like the third set of keys. This is where you have the ability to take up nutrients in the host and to pump out sugars, and to make sure that you start to grow in the tissues.

ADAM BURKE: So it's pretty complex and delicate on the molecular level. We're talking about two species that have both evolved together, and Hoegh-Guldberg believes that co-evolution took a long time.

OVE HOEGH-GULDBERG: I think the problem with this is it's not a single character. It's a whole set of genes, which are involved in symbiosis, which have to be concerted in their evolution. You know, maybe hundreds of genes have to slowly co-evolve with the host to get to a point where they've got this sophisticated and intimate relationship between the two cells.

ADAM BURKE: Now, that's not saying corals can't evolve to cope with increased temperatures. In fact, there's evidence that they can and have. The Great Barrier Reef is 1,400 miles long. Temperatures range from one end to the other, and you can find the same coral symbiont combination living in different locations with different temperature tolerances. So Terry Hughes, who runs the ARC Center for Marine Excellence in Townsville, Queensland, says it's premature to say whether corals will adapt or not.

TERRY HUGHES: Clearly, corals are locally adapted to the temperature regime that they're currently found at. We don't know how long that local adaptation took. It might have taken millennia. So the million dollar question is: Can corals adapt to rapidly rising temperatures? And we don't know the answer to that.

ADAM BURKE: They do know these mass bleaching events can be somewhat selective. Some species are surviving better than others.

TERRY HUGHES: We're already seeing a shift in the composition of species in favor of species that are more resistant to bleaching.

ADAM BURKE: So in the short run anyway, Hughes believes we'll continue to have what he calls "vibrant coral reefs" if we can slow the rate of climate change.

TERRY HUGHES: I don't want to overstate the optimism. I think coral reefs are going to be degraded, but I don't think we're going to see them destroyed in 30 years. We're going to see a shift in species composition, but if we can limit the temperature rise to two or three degrees --

ADAM BURKE: That's four to five degrees Fahrenheit.

TERRY HUGHES: And if we take strong action now, then I think we've got considerable optimism in terms of the future of coral reefs.

JOHN HOCKENBERRY: So Terry Hughes sounds hopeful here. I'm going to have to say it's kind of a relief to hear that reefs won't be destroyed in the short run.

OVE HOEGH-GULDBERG: On the raw face of it, yes, that's correct.

JOHN HOCKENBERRY: There's Ove Hoegh-Guldberg again.

ADAM BURKE: Yeah, and he would tell you that changes that Terry Hughes is talking about aren't just cosmetic.

OVE HOEGH-GULDBERG: I think it's a little misleading to say that they’re going to be anything like a coral reef as we know it today, because corals, I think, will be quite rare organisms. They've got huge ranges. They can reproduce asexually. So there's no problem about corals in the short term as far as extinction, but in terms of their dominance of ecosystems like the Great Barrier Reef, I think they will be rare members of the community.

JOHN HOCKENBERRY: When it comes to extinction, it's difficult to know exactly which species are next, but that doesn't stop scientists from trying to understand how rare species will fare with this climate change business. I mean, I'd want to know if I was next.

ADAM BURKE: Me, too.

JOHN HOCKENBERRY: So just west of the Great Barrier Reef, along the northeast edge of Australia, there are scientists who are studying species at risk. And you went out with them into the woods, Adam, right?

ADAM BURKE: Uh huh.

JOHN HOCKENBERRY: Tell me if I have this right. These are a chain of mountains in Australia known as the Wet Tropics.

ADAM BURKE: That's right. That's right.

JOHN HOCKENBERRY: High altitude, right? Cool, misty rainforest?

ADAM BURKE: That's exactly right. The Wet Tropics are some of the last shreds of an ecosystem that once blanketed Australia, and Steve Williams studies the plants and animals that live only in the Wet Tropics--in other words, found nowhere else in the world. He's an ecologist based at James Cook University in Townsville, Queensland, but more often than not, you can find him out in the rainforest with a research team, documenting biodiversity.

STEVE WILLIAMS: There's another possum way up in the canopy.

ADAM BURKE: Oh, yeah.

STEVE WILLIAMS: There's another lemuroid.

ADAM BURKE: So it's the middle of the night, and we're out with flashlights, counting the marsupial possums that we can spot in the tree canopy. These animals are about the size of a cat. They're hundreds of feet up. You can actually identify them by the color and shape of their eye shine--or, at least, Steve Williams can. We're also on the lookout for other nocturnal animals--owls, bats, a rare species of kangaroo that lives in trees --

JOHN HOCKENBERRY: Oh, man. Dude, you saw kangaroos that live in trees?

ADAM BURKE: Yeah, we didn't see any.

JOHN HOCKENBERRY: Oh.

ADAM BURKE: But one of the students caught a lizard called a leaf-tailed gecko, and we all gathered around--a foot long, mottled green and tan coloring, bulging, yellow eyes.

JOHN HOCKENBERRY: Cool.

STEVE WILLIAMS: You know, these things rely on camouflage. You can see by the pattern. They look like the lichen on tree bark, and their tail is leaf-shaped, which is what gives them their name of leaf-tailed geckos. And even their eyes have a camouflage pattern on them. [laughs] You can hear a little squeak. Hi, cutie.

ADAM BURKE: Wow, they are really beautiful.

STEVE WILLIAMS: Oh, yeah, they're fantastic, one of my favorite animals.

JOHN HOCKENBERRY: With a tail shaped like a leaf and yellow camouflaged eyes --

ADAM BURKE: It looks like a creature from another planet.

JOHN HOCKENBERRY: Ah, man.

STEVE WILLIAMS: The belly is just like soft as silk, isn't it?

STUDENT: Yes.

STEVE WILLIAMS: Here, feel the belly.

STUDENT: Uh.

ADAM BURKE: Can I feel the belly, too? [Gecko squeaks.] Oh. [laughter]

ADAM BURKE: In the last few million years, climate has fluctuated wildly in the Wet Tropics. For example, the last Ice Age, 18,000 years ago, caused the region to dry out considerably, leaving just tiny islands of cool misty rainforest on a few mountaintops.

STEVE WILLIAMS: As the rainforest contracts, each one of those mountaintops becomes more and more isolated and smaller and smaller area. Sometimes if it gets too small, the rainforest completely disappears, the populations in that area would have gone extinct. And as the rainforest has expanded again, over the last 5,000 years, species have been able to re-colonize those mountains.

JOHN HOCKENBERRY: So climate has crunched the forest down to these tiny isolated pockets, and then they've expanded out again and crunched down again, and expanded out again.

ADAM BURKE: And the tiny isolated pockets that remained became kind of these life rafts for many species of vertebrates. That's where they hunkered down and rode out the dry times. Creatures like the lemuroid ringtailed possum.

JOHN HOCKENBERRY: And I'm almost afraid to ask, the tree kangaroo?

ADAM BURKE: Yup, and the tree kangaroo, and birds, and frogs, and our friend, the leaf-tailed gecko.

JOHN HOCKENBERRY: Your friend.

ADAM BURKE: My friend. All of these different critters survived in tiny patches of forest that were left on mountaintops.

JOHN HOCKENBERRY: So whatever happened to your little leaf-tailed gecko pal? I mean, what did the scientists do with it?

ADAM BURKE: Well, they weigh it and measure it, record the coordinates where it was found, and they take a DNA sample.

JOHN HOCKENBERRY: That's interesting--I don't know how interesting for the gecko, but it's interesting.

ADAM BURKE: It is really interesting. Part of the story of past climate change can be found in the genes of these animals.

JOHN HOCKENBERRY: Really?

ADAM BURKE: Yeah, which is why Steve Williams is working with a population geneticist named Craig Moritz at the University of California, Berkeley to decode this story of past isolation.

CRAIG MORITZ: Take a population down to a very small size, it loses a lot of those genetic variation, and that loss of genetic variation takes a long time to recover. You have to get it back by mutation, and that takes tens of thousands of years to do. So there's a record of history sitting in the DNA that we can use to try and estimate what was the population size like through time from the pattern of variation.

ADAM BURKE: So for example, if a population of leaf-tailed geckos were confined to a mountaintop thousands of years ago, that population is going to have a recognizable genetic signature.

JOHN HOCKENBERRY: Just because of a mountain? Why?

ADAM BURKE: Well, remember, Craig Moritz said, "Take a population down to a very small size, and it's going to lose a lot of its genetic variation." Okay, here, let's think about it this way. See this bag of candy?

JOHN HOCKENBERRY: This bag of candy right here?

ADAM BURKE: That bag of candy.

JOHN HOCKENBERRY: Wow.

ADAM BURKE: There are 13 different colors of jellybeans inside.

JOHN HOCKENBERRY: You've already inspected this?

ADAM BURKE: I have already inspected it. Now, reach in, grab a small handful, and put them in that bowl.

JOHN HOCKENBERRY: All right.

ADAM BURKE: Just a small handful, John.

JOHN HOCKENBERRY: All right. There's some for you, don't worry.

ADAM BURKE: Okay. So what colors do you have?

JOHN HOCKENBERRY: All right. I've got some dark blues, two yellows, a brown one, some red ones.

ADAM BURKE: So just four of the 13 colors.

JOHN HOCKENBERRY: Yup, that's all I got.

ADAM BURKE: So it's not really a surprise, right, that there's going to be less variety in the bowl --

JOHN HOCKENBERRY: I see.

ADAM BURKE: Than there is in the whole bag? I mean, odds are really low that you're going to have all of the colors, right?

JOHN HOCKENBERRY: Right. So 13 colors in the bag, only four in my little bowl here.

ADAM BURKE: The same thing happens with leaf-tailed geckos when their habitat crunches down to a little island on a mountaintop.

JOHN HOCKENBERRY: Right.

ADAM BURKE: That bag represents the diversity before the crunch. The candy in your hand represents the genetic diversity of geckos remaining on a particular mountaintop after the crunch.

JOHN HOCKENBERRY: Okay.

ADAM BURKE: Okay. So now reach in the bag and get another handful and tell me the colors.

JOHN HOCKENBERRY: All right. All right. We've got one brown, some yellows, some orange ones, and some green ones.

ADAM BURKE: So that represents the genetic diversity of geckos on another mountaintop.

JOHN HOCKENBERRY: Different combinations of colors.

ADAM BURKE: And each combination represents a different genetic signature.

JOHN HOCKENBERRY: Which allows our geneticist Moritz to tell descendants of one population from another.

ADAM BURKE: Exactamundo. So they start with some genetic data collected from leaf-tail geckos throughout the Wet Tropics.

CRAIG MORITZ: So we look at the leaf-tail geckos, we see two genetic groups. Within each population, the level of variation is exceptionally low, which suggest they contracted back to a very small population.

ADAM BURKE: And because they mapped where each genetic gecko sample came from, they know something about where these creatures survived during the rough times.

CRAIG MORITZ: There are different numbers of genetic clusters, if you like, within each species. So the leaf-tail gecko had just two--one north, one south--a very, very clear picture. In others, there could be five or six or seven different genetic groups, which implies that they survived the glacial periods in multiple places.

ADAM BURKE: There are actually a whole range of genetic signatures that tell Moritz where species hunkered down, where they went locally extinct, and how long it took them to spread back out again.

JOHN HOCKENBERRY: It's like DNA's a map. I mean, Steve Williams is out there, running around in the woods, catching lizards and frogs, and taking tiny tissue samples, which he sends to Craig Moritz.

ADAM BURKE: And Craig Moritz uses the genetic signatures to reconstruct a story of how that map has changed over time for the gecko and many other species in the Wet Tropics.

CRAIG MORITZ: It's like trying to read molecular tea leaves. You know, whoa, what's in the bottom of the cup, and what did that mean about the past? You need to draw multiple lines of evidence, and it's when you put all the different lines of evidence together, we can build up a fairly consistent picture of what happened.

ADAM BURKE: Williams and Moritz are also using their information to estimate how these species are going to cope with rising temperatures now, based on what happened in the past.

JOHN HOCKENBERRY: How much warming is predicted here?

ADAM BURKE: Between three and ten degrees Fahrenheit.

JOHN HOCKENBERRY: That Fahrenheit thing again. And what do they say will happen to the Wet Tropics species?

ADAM BURKE: Similar to what happened in the past. As temperatures increase, these species will retreat up to the highest reaches of the mountains until there's nothing above but blue sky.

CRAIG MORITZ: I think the consensus at the moment is that this is a type of climate that these fauna simply haven't experienced in the last few million years, and these species, which formerly evolved in much cooler, wetter climates are going to get hammered. So I desperately hope these models are wrong, and we're doing everything we can to disprove them.

JOHN HOCKENBERRY: Coming up, a species that is changing the climate. This is "The Heat is On: Evolution in Action." We'll be back in a minute.
...
JOHN HOCKENBERRY: This is The DNA Files. I'm John Hockenberry, and Adam Burke is with me. Adam?

ADAM BURKE: Hi, John.

JOHN HOCKENBERRY: So we've been talking today about how a little bit of climate warming over the past century--just 1.2 degrees on average has already shaken up the biological world, and is pushing species towards extinction. But what we tend to forget in all this is how ordinary extinctions are--Earth, you see, is not a stable place. It never has been. You've got continents moving around. You've got changes in temperature, changes in ocean chemistry. You've got volcanoes, even asteroids hitting the earth.

STEVE JONES: At the end of the Permian Era, 241 million years ago, there was a massive extinction.

JOHN HOCKENBERRY: That's evolutionary biologist Steve Jones of the University College, London.

STEVE JONES: Over 90% of all creatures disappeared. Whole groups of animals like the trilobites--one of the most abundant of all, just went. Fortunately, a few things were left, and the evolution went back almost to the beginning of the chess game and started again.

ADAM BURKE: Lucky for us. [laughs]

JOHN HOCKENBERRY: [laughs] That's right, and you might see this as a story of resilience, but it also reminds us that even the most robust life on earth could be a hair's breadth away from the whirling blades of extinction, at least if you consider evolutionary time.

STEVE JONES: I often think of natural selection as a factory--a factory for making almost impossible things--you're an almost impossible thing. I am. Every bird is, every plant is, every bacterium is. You and I and all those other creatures stand at the summit of an enormous mountain of extinct life--creatures which did not survive to pass on their genes.

JOHN HOCKENBERRY: It's amazing. Jones is describing an entire parallel universe of extinct life. Our current warming trend here on earth could add another heap of species to that collection of extinct organisms. It kind of makes me wonder. What kind of a world are we headed for here?

STEVE JONES: Evolution in some ways is the triumph of the weeds, and the weeds are already taking over. Climate change is going to make it worse.

ADAM BURKE: I don't suppose Jones is talking about dandelions or crabgrass.

JOHN HOCKENBERRY: Uh not really, but sort of. I mean, he is talking about all the species that can live in a wide range of habitats. You know, the cockroaches, the raccoons, the coyotes--

STEVE JONES: And the weediest species of all, of course, is Homo Sapiens, in the sense that we're the species that's come and ruined everybody else's habitat and trampled all over it for our own delectation rather than staying rare, specialized, and rather beautiful in a valley in East Africa.

JOHN HOCKENBERRY: Get used to it, folks. Homo Sapiens, the ultimate weed. We live on almost every continent, and in almost every climate on earth. Why didn't we remain rare, specialized, and beautiful in a valley in East Africa?

ADAM BURKE: I got a theory to share.

JOHN HOCKENBERRY: Well, aren't you just the little theory meister here?

ADAM BURKE: It's a good one.

JOHN HOCKENBERRY: Okay, let's--let's hear it.

ADAM BURKE: Okay, good. So anthropologists have long theorized that climate change played a role in making humans the wily generalists that we are.

JOHN HOCKENBERRY: [laughs] Oh, you wily generalist, you. But I've heard that theory. Five millions years ago, human ancestors were living in dense forests, and then when East Africa transitioned into an open grassland environment all of a sudden, our ancestors had to come up with a very serious Plan B.

ADAM BURKE: Yeah, and anthropologist Rick Potts of the Museum of Natural History in Washington, D.C. says this was a prevailing theory for a long time.

RICK POTTS: We kind of all thought that we knew what the setting was, that basically Africa dried out, and that was the cauldron in [laughs]--in which human evolution took place. It bubbled along, and out came new adaptations to the challenges of the open grasslands.

JOHN HOCKENBERRY: That sounds like the standard evolutionary story.

ADAM BURKE: Well, it is. The environment changes, and human ancestors evolved to cope with the new environment, giving rise to the many things we prize in ourselves.

JOHN HOCKENBERRY: Like tool use, like walking upright, social cooperation, hunting, meat eating.

RICK POTTS: And you could basically unfurl all the different qualities that we are so proud of in terms of human uniqueness just by getting early humans into one environment.

JOHN HOCKENBERRY: Now, as I'm listening, I assume there's a flaw in this theory, right?

RICK POTTS: Well, the problem with that is that there's no longer any evidence for it.

ADAM BURKE: Now, East Africa is drier than it was five million years ago, but when you consider multiple sources of climate data, things like ancient pollen samples, lake beds, sediment cores from the Indian Ocean --

RICK POTTS: None of that indicates that the savanna was contemporaneous with the earliest evidence of fossil humans. And so, the question is: Well, what is the environment?

ADAM BURKE: It turns out it wasn't any one environment at all. Rick Potts turned to paleo-climate modelers like Peter DeMenocal of Columbia University. And DeMenocal says East Africa saw dramatic climate swings between wet and dry over the last five million years, or as he puts it, there were greener times and browner times.

PETER DEMENOCAL: Greener times with more vegetation, browner times with less vegetation.

JOHN HOCKENBERRY: So in some periods, rainfall increased, and forests expanded. In others, rain was more scarce, and things dried out.

ADAM BURKE: Right, but remember this swinging back and forth is happening over periods of tens of thousands of years. DeMenocal's data lets him watch these fluctuations like a movie.

PETER DEMENOCAL: If you were to play this movie, you would see this pulsing of greener times and browner times, going back and forth, but then as we move toward the present, you notice that the range of variations increases as well.

ADAM BURKE: In other words, there were times--stretches of a few hundred thousand years where the swings between wet and dry became more dramatic.

JOHN HOCKENBERRY: So greater contrast between the wet, wet and the dry, dry during these periods.

ADAM BURKE: Yeah, and Rick Potts began to believe that the increase in climate variability was an important piece of the human evolution story.

RICK POTTS: It dawned on me that we really didn't have any idea about what that meant. We always treated it as just noise in the signal. [laughs] The signal represented the constant qualities of environments, the stable qualities, but to my mind, the variability might itself represent a very important signal of uncertainty and unpredictability that might help us understand the emergence of new adaptations, new traits.

ADAM BURKE: This is something Potts calls variability selection, and the idea is that environmental instability over long periods of time will favor organisms that can cope with a range of environments.

RICK POTTS: What ultimately will survive that are those genes and those strategies of behavior that allow versatility, allow versatile or adaptable response to when things do change.

ADAM BURKE: What's interesting is that the fossil record of human ancestry seems to bear this idea out. For example, take the well-known fossil, Lucy.

JOHN HOCKENBERRY: Oh, yeah, I know her--female, about 3.2 million years old, discovered in Ethiopia in the mid-1970's, likes to date anthropologists.

ADAM BURKE: That's the one. Lucy is the most famous fossil member of a species called Australopithecus afarensis. Lasted in Africa for one million years in a region that fluctuated dramatically between wet and dry.

RICK POTTS: What was amazing is that Lucy's lineage was found in all of the layers through all of these different environmental changes, and Lucy was an amazingly adaptable early human, even without a large brain and stone tools. Lucy's lineage, Australopithecus afarensis, became extinct some time around 2.9, 2.8 million years ago, and that's a time when the amount of environmental fluctuation in Africa increased even more, more than it was during Lucy's time.

ADAM BURKE: Around the same time, two new hominids emerge--including the earliest appearance of our own genus, Homo, the first hominid with a slightly larger brain.

RICK POTTS: And what's interesting is that what comes out of Lucy's extinction is the emergence of two new branches in the human family tree that are more adaptable than Lucy was.

ADAM BURKE: So Potts argues environmental instability rewarded those that could branch out and diversify, and he lumps cultural innovations in there, too. This same period, 2.8 to 2.5 million years ago, marks the earliest evidence of eating meat and the earliest evidence of stone tools, which Potts says was like getting access to a whole new set of teeth.

RICK POTTS: All sorts of different foods open up to the possibility of being processed with these stone tools, with these teeth outside of your body.

ADAM BURKE: Stone tools were an early indication that human ancestors were becoming more adaptable, not only by evolving new physical characteristics, but by tinkering with the environment and sharing their know how with each other.

JOHN HOCKENBERRY: So better brains meant more elaborate cooperation, snazzier tools. We get language, agriculture--all these are adaptive responses to a volatile environment

ADAM BURKE: That's what Potts argues.

RICK POTTS: We are tinkerers. We change, and we like to change everything. And what we face right now is an experiment in earth's climate that has never really been tried. We are now a new factor on the volatile planet. It's not that the planet is inherently stable. We know that that's not the case. The problem is is that we're now pulling on some of the same strings that have in the past led to climate change and led to extinctions.

JOHN HOCKENBERRY: Okay, that's a problem, but to deal with it, we've got our plasticity and our adaptability as a species, an evolutionary product of a volatile world, right? I can feel good. But I have a feeling that there are people who disagree with Potts, right?

ADAM BURKE: Sure, there are other theories on what drove human evolution and then some anthropologists say it's an interesting idea with no conclusive data.

JOHN HOCKENBERRY: But whatever disagreement there may be about the mechanisms that drove human evolution, I mean, [laughs] few can argue about the net result. We're doing pretty well here.

ADAM BURKE: It's hard to argue with the reality of 6.7 billion Homo Sapiens.

JOHN HOCKENBERRY: That's right. [laughs] We talked with a guy who spent his life thinking about human population numbers, Paul Ehrlich of Stanford University. He says the way we have literally infested the planet is a kind of evolutionary success.

PAUL EHRLICH: One can argue about whether certain bacteria or so on are dominant over us, but there's no question that as animals go, we're the top dog on the planet.

JOHN HOCKENBERRY: And it's those very same human top dog qualities forged over the last five million years that Ehrlich says explains why we have become the life of the party here on earth.

PAUL EHRLICH: So we have a relatively small, but very effective set of genetic information, which produces among other things this marvelous brain and the capacity to manipulate gigantic amounts of cultural information.

JOHN HOCKENBERRY: We pass along our genes, and in a similar way, we pass along our culture. Ehrlich argues that culture is what gives Homo Sapiens the power to respond to environments in very rapid and sophisticated ways. In early human societies, you didn't need to invent stone tools from scratch every generation. You could learn how to make them from your pals. In modern societies, we screw in the light bulb and flip the switch without ever needing to know how to make one. We evolve to do this, and we do it very, very well.

PAUL EHRLICH: Human beings have become dominant by manipulating their environments. In other words, rather than just reacting to whatever the environment does, we change environments, and that's what we're still doing. We are now changing the environment of essentially every organism on the face of the planet.

JOHN HOCKENBERRY: And now we've tilted the climate systems, too. It's an unintended byproduct of the human way of life, but the reality of climate change challenges Homo Sapiens to change the way we live, and the stakes are high. Rising sea levels, disrupted food supplies, rising temperatures that could throw Earth's systems into ecological chaos.

PAUL EHRLICH: So it's basically a problem in cultural evolution. How do you transform what we know scientifically and what we know we should be doing into actual social action? And there's lots and lots of things we could be doing this very day. So the issue is: Why don't we use the tools we've evolved?

ADAM BURKE: Yeah, John, why don't we?

JOHN HOCKENBERRY: You're asking me?

ADAM BURKE: I'm asking you.

JOHN HOCKENBERRY: You're asking me?

ADAM BURKE: [laughs] I'm still asking you.

JOHN HOCKENBERRY: Well, I was thinking of the story Rob Boyd tells. He's an anthropologist from UCLA.

ADAM BURKE: And that would be the story of?

JOHN HOCKENBERRY: You know the story. You know the story. Eric the Red.

ROB BOYD: Eric the Red settled in Greenland from Iceland right around 1000 A.D., and there was a fairly thriving community of Norse settlers on the southwest coast of Greenland. Think of these people living on, you know, beautiful, grassy valleys on the edge of fjords and stone houses, and living and marrying and drinking, and doing all of the things that people did.

JOHN HOCKENBERRY: So there they were --

ADAM BURKE: Minding their own Nordic business.

JOHN HOCKENBERRY: Growing hay in summer and storing enough to last the winter months, and it lasted that way in Greenland for a few hundred years, and then the little Ice Age happened.

ROB BOYD: When it got a little colder, it shifted the balance so that the system they had--the Norse economic system stopped working.

ADAM BURKE: Uh what does he mean it stopped working?

ROB BOYD: There were occasional visits from trading ships from Iceland, and the last one came, and everyone was dead.

JOHN HOCKENBERRY: Meanwhile, living up the coast, there were Inuit hunter gatherers who also had to brave the little Ice Age, but they survived in different ways.

ADAM BURKE: What, kayaks? Harpoons? A delicious seal diet?

JOHN HOCKENBERRY: Hey, Adam, what are you doing? Reading ahead? Yeah, that's what they did.

ROB BOYD: And the interesting thing is, there was lots of contact between the Norse and the Inuit, and so even though their neighbors were a success, the Norse never copied this way of life from their neighbors, and stuck to their guns, and in the end, went out of business.

JOHN HOCKENBERRY: Score one for the Inuit. So the question, of course, is: Why? Why did these Norse settlers starve to death when the keys to survival were right in front of their highly evolved, adaptive faces?

ADAM BURKE: You know what I would have done?

JOHN HOCKENBERRY: What?

ADAM BURKE: I would have put down my horned Viking hat and started taking harpoon lessons from my Inuit buddies.

JOHN HOCKENBERRY: Some Viking you are. I mean, you're a sensitive, international guy, Adam. Of course, you would have done that. And maybe there were some Nordic folks who traded their myths for mukluks, but not enough did. Most didn't. No one knows why for sure, but Rob Boyd thinks that culture had something to do with it.

ROB BOYD: So even though, the Inuit system seemed to be better, you could see a--a Viking guy thinking, "Well, my neighbors will think it's ridiculous if I stop farming and start paddling around in a kayak. That's not what we do. That's what those other people do." And so I think that it's completely understandable how this happened, but it does illustrate that despite the fact that we're great adapters, sometimes we--we don't adapt well enough.

JOHN HOCKENBERRY: So culture is kind of our mixed blessing. It's brought humankind a long, long way. But sometimes culture also prevents us from recognizing the path to survival, even if it's right there in front of us.

ROB BOYD: We have the capability of adapting that's unprecedented, I think, and that comes from the fact that we have these cultural tools, which let us adapt non-genetically on really rapid time scales, but whether we'll channel those in our collective interests, that's the hard question.

JOHN HOCKENBERRY: Hard question? Hard question? [laughs] That is the only question. There is no other question than this.

ADAM BURKE: Okay. So where does that leave us?

JOHN HOCKENBERRY: Well, it seems like it leaves us facing the same mind boggling global problem we started with, Adam. I mean, climate change is going to hit us, right?

ADAM BURKE: Right. I mean, it's already hitting us.

JOHN HOCKENBERRY: The question is: What human changes is that going to bring?

PETER DEMENOCAL: Right now, we're dealing with an earth that's warming, because of human activities. That's just the fact, Jack.

CAMILLE PARMESAN: The climate space in which species now exist is gone if we have business as usual.

CRAIG MORITZ: Humans are just one species of perhaps 10 million on the planet.

CHRISTINA HOLZAPFEL: Who among us cannot give up one or two luxuries?

WILLIAM BRADSHAW: If all we could do is slow the process of climate change, we would provide greater opportunities for plant and animal communities to adapt.

PAUL EHRLICH: We're either as a culture--and we're a global culture in this sense with this problem--we're either going to solve it as a global culture or we're not going to solve it as Homo Sapiens.

JOHN HOCKENBERRY: Ehrlich said it. We are an evolutionary experiment living on the edge.

ADAM BURKE: An almost impossible thing.

JOHN HOCKENBERRY: I love that. A hominid with a big adaptable brain.

ADAM BURKE: Capable of unlocking Nature's secrets and solving the puzzles inside.

JOHN HOCKENBERRY: And whether we like it or not, we are the authors of the latest chapter in the human evolutionary story. What do you out there think should be written? Here with Adam Burke, I'm John Hockenberry. Thanks for listening to The DNA Files.

CREDITS:
To find out more about climate change, evolution, and genetics, visit our website at dnafiles.org where you can download a podcast of this program. This series, The DNA Files, was produced by SoundVision Productions with funding by the National Science Foundation, U.S. Department of Energy, National Institutes of Health, and the Alfred P. Sloan Foundation. This program, "The Heat is On: Climate Change and Genetics" was produced by Adam Burke. The DNA Files is managing editor, Loretta Williams, editor, Deborah George, science content editor, Sally Lehrman. Research director is Adi Gevins. Production support by Noah Miller, Julie Caine, and Raynelle Rino. Office support provided by Steve Nuñez and Beverly Fitzgerald. Our web director is Ginna Allison. Technical engineer and music director is Robin Wise. Our host is John Hockenberry. Our theme music was composed and performed by Steve White. Additional music by Adam Burke, Conrad Praetzel and Robert Powell. Marketing of The DNA Files is by Schardt Media. Legal services by Cooper, White and Cooper and Spencer Weisbroth. Special thanks to Murray Street Productions. Send your responses and letters to feedback@dnafiles.org. For CDs and transcripts, call 888-303-0022. That's 888-303-0022. The executive producer is Bari Scott. This has been a SoundVision production, distributed by NPR, National Public Radio.

The DNA Files:
Unraveling the Mysteries of Genetics

As heard on National Public Radio

Rewriting Heredity: Environment and the Genome

Hosted by John Hockenberry

Transcript

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and the Alfred P. Sloan Foundation.
JOHN HOCKENBERRY: This is The DNA Files. I'm John Hockenberry. In the next hour, a collision with the American diet leaves an indigenous people reeling from runaway obesity.

PETER BENNETT: They had an extremely high prevalence of diabetes that was estimated to be eight to ten times higher than in any other population in that particular time. In truth, we had really no idea what the underlying causes were.

JOHN HOCKENBERRY: Meanwhile, in the Court of Long Beach, an asthma epidemic, but the sufferers tend to be related.

KARENA HAMILTON: My mom takes daily medicine for it, an inhaler, and my sister does as well and her daughter.

JOHN HOCKENBERRY: And scientists are learning that our genes and the environment are entangled in an embrace that may alter our legacy to our children and our children's children. Join us for "Rewriting Heredity: Environment and the Genome" after the news.
...
JOHN HOCKENBERRY: This is The DNA Files. I'm John Hockenberry.

Welcome to New York City, eight million sharp elbowed homo sapiens, crowded together, breathing, eating, jostling.

JOHN HOCKENBERRY: Hi, how are you doing?

JOHN HOCKENBERRY: Each one a little different, but all immersed in the same complex environment. Truck exhaust. [laughs] There's somebody smoking over there. That means I'm smoking.

JOHN HOCKENBERRY: Sorry. It's okay. It's fine. I don't want to cause a fight.

JOHN HOCKENBERRY: Like pedestrians in a crowded city, the chemistry of the human body is constantly being bumped and elbowed by the environment -- pollution, pathogens, stress --

JOHN HOCKENBERRY: Whoa. Hey. What are you trying to do, kill me? Hey, you almost ran over me, what's going on?

JOHN HOCKENBERRY: Even what you eat and drink affects the chemistry inside your body where the crucial genetic machinery does its work. From the gene's point of view, your diet is part of the environment, but each one of us responds to this environment a little differently. Hang on a second.

JOHN HOCKENBERRY: Hot dog? Hot dog?

VENDOR: Hot dog? How many?

JOHN HOCKENBERRY: Yeah, with everything. One.

VENDOR: Okay.

JOHN HOCKENBERRY: With everything.

VENDOR: Okay.

JOHN HOCKENBERRY: I mean, everything.

VENDOR: Okay.

JOHN HOCKENBERRY: Take this New York delicacy, for example.

JOHN HOCKENBERRY: Oh, yeah.

VENDOR: 2, 3, 4, 5. Thank you very much.

JOHN HOCKENBERRY: Change.

VENDOR: Have a nice day.

JOHN HOCKENBERRY: All right. Thanks so much

JOHN HOCKENBERRY: A hot dog wolfed down on the street isn't on anybody's celebrity diet plan, but some people can eat anything, and never gain a pound, while others diet constantly, and just can't seem to lose weight. Well, no mystery there. It's genetic, right? Some people are just naturally slim. So, then why is America suddenly in the midst of an obesity epidemic? Are we all changing genetically?

For nearly a century, geneticists have searched for the code that makes one person fat, another thin, one sickly, the other robust. The quest has drawn them into a labyrinth of genetic pathways and environmental turning points, the plan of which is still unknown. In the American Southwest, one historically isolated population has been devastated by unprecedented rates of obesity and diabetes. For more than 40 years, scientists have been asking why. Producer Vicki Monks reports from Arizona.

VICKI MONKS: An hour before sunrise, 15 Tohono O'odham runners leave their encampment on the sacred mountain southwest of Tucson, Arizona, descending the mountain, moving across the desert floor. The runners are lean, athletic, conditioned to the Sonoran desert heat that's pushing over 100 degrees before 10 AM.

Runs similar to this one have been part of sacred ceremonies going back longer than memory. Not so many years ago, nearly all the Tohono were as fit and healthy as these runners, but now, too many people are overweight, in wheelchairs. Some have amputated feet or legs from diabetes. Tohono are Pima Indians who have inhabited what is now the American Southwest for millennia. Their cousins, a bit to the north, occupy reservations on the Salt and Gila Rivers bordering the Phoenix metropolis.

Epidemiologist Peter Bennett visited the Pimas at Gila River in the 1960s to study rheumatoid arthritis, hoping to find arthritis free populations in this hot, dry climate. The study was a disappointment. There was plenty of rheumatoid arthritis among the Pima, but he noticed something else.

PETER BENNETT: They had an extremely high prevalence of diabetes that was estimated to be eight to ten times higher than any other population in that particular time. Of course, we didn't know why it was so frequent. One hypothesis was simply that the Pimas might have been a genetic isolate, and for some unknown reason, those few people with diabetes genes had multiplied and formed the Pima tribe. That was one hypothesis.

VICKI MONKS: Another hypothesis was that some environmental agent was responsible.

PETER BENNETT: Another pretty wild idea, but nevertheless one that we examined at least to some extent was that perhaps the toxins provided by scorpion bites would precipitate diabetes, because there was some fractional evidence that the toxins in scorpion bites would actually cause hypoglycemia in I believe it was mice, if I recall correctly. So, that was one possibility, and of course, that fell flat on its face, too. We could find no evidence that there was an excess of scorpion bites among those who had diabetes as compared to those that did not. In truth, we had really no idea what the underlying causes were.

VICKI MONKS: Diabetes and obesity are closely linked. Obesity is the greatest risk factor for adult onset diabetes that usually develops after age 35. Bennett began to look for high rates of diabetes or obesity in other populations. By that time, he had been joined by other researchers with their work funded through the National Institutes of Health. The team discovered another desert tribe with extraordinarily high rates of both diseases -- the Tohono O'odham, closely related by language and culture, to the Pimas at Gila River. That discovery reinforced the plausibility of a genetic explanation, but what was it, and how might it work? Eric Ravussin, a young specialist in obesity joined the team in Phoenix to investigate how the Pima might be examples of the thrifty gene hypothesis, first postulated in 1962 by pioneering human geneticist, James Neel.

ERIC RAVUSSIN: And he postulated the hypothesis that diabetes has to be associated with a survival advantage. He didn't know what it was.

VICKI MONKS: According to Neel's scenario, the ability to store fat conveyed an evolutionary advantage.

ERIC RAVUSSIN: Larger weight was a good thing in the history of mankind. It's only over the past 70 years that it's becoming a bad thing. Our genome, which has been modified over thousands of years have been adapted to scarcity of food and not abundance.

VICKI MONKS: Eric Ravussin and other NIH researchers embarked on a more than 40 year quest to find evidence of a thrifty gene operating in the Pima Indians. Along the way though they discovered several things about how and why people gain weight, and why it's so difficult to lose it. But to understand, we need to back up and follow the path the Pimas took into the modern world.

WOMAN: Squash, cheese, uh shredded beef, green chile, corned beef, red chile burro, and bean and cheese, and soda.

VICKI MONKS: In Sells, Arizona, on the Tohono O'odham reservation, everyone drives cars these days. So, it's the parking lots where vendors do their best lunchtime business. You can buy pork tamales, pizzas, sodas -- high fat, high calorie quick food.

TERROL DEW JOHNSON: You know, I used to drink at least a 12-pack of soda a day. Two, three in the morning, two, three for lunch, two and three or four for dinner.

VICKI MONKS: At 6 feet tall and 300 pounds, Terroll Dew Johnson seems an unlikely figure to be the leading health advocate on the reservation, but over the past 12 years, his organization, Tohono O'oodham Community Action or TOCA has been fighting some of the more destructive effects of modern life by helping people reclaim traditional diets.

TERROL DEW JOHNSON: This is the food the Creator gave us. This is what kept the people in a desert, where there's hardly any rainfall, alive for thousands of years.

DANIEL LOPEZ: Sometimes we just walked out in the desert to look for mesquite bean when they were in season. That was our sweet. The mesquite sap called usabi

VICKI MONKS: Daniel Lopez was born in 1936 when most Pimas still held to traditional ways, relying on desert plants for food. Cholla buds, mesquite beans, wild spinach, the sweet red fruit of the saguaro cactus, and there was plenty of physical activity.

DANIEL LOPEZ: Well, we didn't have TV. We didn't have Game Boys, but our playground was the desert, and the girls were over there by this clearing near the ceremony house, and they're playing the woman's game called Toka. I mean, you're running back and forth -- that's a very active, strenuous game, the same thing with the kickball that the boys played. We ran all the way up there, barefooted, you know. But we did it back then.

VICKI MONKS: But changes were coming fast.

DANIEL LOPEZ: Maybe around the 1940s, the cotton field era came in, and the farmers would come out and recruit O'odham families to go and pick cotton. That's when I say the traditional farming began to decline, because so many people were gone, because to go to the cotton field, chop cotton, starting May, then pick cotton, starting about September, and yet you plant in the summer time. That's when you plant it traditionally with corn, beans, and squash, but now the farmer take it to the store, and you can purchase your canned goods, your bread, your soda, your candy, probably the things that we shouldn't have been eating, but this was things available, you know. We had no choice. That's the only thing we could eat, you know.

VICKI MONKS: Then came World War II.

TERROL DEW JOHNSON: My grandfather was in the Navy. He was taken from his farm and put on a boat where he learned how to cook doughnuts.

VICKI MONKS: When the war ended, Terrol Johnson's grandfather couldn't find a job on the reservation. So he improvised.

TERROL DEW JOHNSON: He made doughnuts in the village and would sell them to people to make maybe one cents or two cents. People loved it, because it was something different.

VICKI MONKS: By the 1950s, the pressures to abandon traditional lifestyles intensified and the disruptions that began with the cotton fields and the war accelerated. As Arizona cities grew, so did demands for water. So the federal government stepped in with money to dam the rivers. That brought traditional farming to an end, and pushed Pimas into the cash economy, earning the lowest wages. Healthy eating can be expensive, and there was the pressure to fit in.

DANIEL LOPEZ: We could eat like you guys, you know -- eggs and ham and all that. The thing is mindset, you know. But we wanted to be like the dominant culture -- dress like them and talk like them, eat like them.

VICKI MONKS: Of course, Pimas value modern innovations as much as anyone else. The Internet's an important tool on the reservation, and without cars to travel vast expanses of desert, it could be nearly impossible today for the Tohono O'odham to hold jobs or carry on business. But changes over the past 60 years have been disastrous for Pima health. College professor Tony Chana recalls his own diagnosis with diabetes in 2002, when he was 63 years old.

TONY CHANA: My blood sugar was over 500. They put me on IV and said that I was critical. And when I was lying there, taking the IV, I thought about all the kinds of things that people who have diabetes seem to go through -- many of my friends who have diabetes where they've lost their toes, some of them who eventually died from failure of heart or something like that -- diabetes related, I'm sure. Now I see it in people younger than myself, and it's tragic, even kids who have diabetes.

VICKI MONKS: More than three-quarters of older Pima adults have diabetes, and this adult onset disease is now showing up in Pima children as young as 7. Obesity among children is the culprit.

JOHN HOCKENBERRY: When The DNA Files returns, measuring a metabolism. This is "Rewriting Heredity: Environment and the Genome." I'm John Hockenberry. We'll be back in a minute.

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JOHN HOCKENBERRY: Welcome back. This is The DNA Files. I'm John Hockenberry. It was a promising hypothesis -- a tribe living where food was scarce might harbor a thrifty gene that promoted fat storage. One way such a gene might work is by lowering the rate of metabolism. Perhaps the Pima was fat, because they conserve more calories. Investigator Eric Ravussin's team began the painstaking work of measuring the metabolic rate of the Pimas, one individual at a time. And in Phoenix, they built a special sealed room called a metabolic chamber to do the measuring, a facility much like this one, back on the streets of Manhattan, at Columbia's New York Obesity Research Center.

DR. ALLAN GELIEBTER: A metabolic chamber is used to measure the amount of energy that an organism consumes by measuring the amount of oxygen consumed and carbon dioxide produced.

JOHN HOCKENBERRY: Dr. Allan Geliebter is a senior research scientist to Columbia University. In metabolism, you'll remember, the body consumes oxygen, and produces carbon dioxide. Got it? So a person in a sealed room gradually changes the composition of the air. You may have noticed this. The faster their metabolism, the faster the change. So as the air in the room is gradually refreshed, scientists can measure the gases in this outgoing air.

JOHN HOCKENBERRY: It looks like a regular hospital room, sort of, but uh we've got the vacuum door there.

JOHN HOCKENBERRY:There's a sink and other necessities for a 23 hour visit. Tasty meals arrive periodically through an airlock.

DR. ALLAN GELIEBTER: No, we'd rather people in here are not bored. We do have some nice videos.

JOHN HOCKENBERRY: The Abyss, Special Edition, Fargo.

DR. ALLAN GELIEBTER: It's one of my favorites, Fargo. There's a window they can look out.

JOHN HOCKENBERRY: And if you put up a little "Help Me" sign, you can just put it up to the window there.

JOHN HOCKENBERRY: In Phoenix, more than a thousand people spend up to a week in Eric Ravussin's metabolic chamber, but the researchers found no evidence that the Pima had a thrifty metabolism. Then the investigation took an unexpected turn with the discovery of another native population in a remote part of Mexico. They were also Pima, and they were thin. Vicki Monks picks up the tale.

VICKI MONKS: The village of Maycoba nestles beneath dramatic cliffs in Mexico's Sierra Madre Mountains. Traveling there can be risky. Livestock or fallen rocks often block the narrow highway. In the mid-90's, when scientists first came here, the road had just opened. Before that, if you wanted to get to Maycoba, you could drive down a steep gorge and through the river or take your chances on a rickety footbridge.

In a highland meadow near Maycoba, Pima elder Jose Angel Galaviz is constructing a wooden plow for planting corn. It's built on the same design used by his ancestors who inhabited this region for at least 500 years, when it's believed they drifted apart from their Pima cousins in Arizona. Wiry, thin, and muscular, like most of the Pimas here, Angel is fit by default. Survival for Maycoba Pimas depends upon constant work.

JOSE ANGEL GALAVIZ: (speaks Pima)

INTERPRETER: One person turns the ground with burros or with oxen, and the other goes to plant, and then the corn is born. When the cobs are there, then you start to pick -- to pick the corn. So from there, we can feed all of the indigenous companions for the whole rest of the year.

VICKI MONKS: Scientists working with the National Institutes of Health who had been studying the Arizona Pimas wondered if the Maycoba Pimas could help prove the thrifty gene theory. They reasoned that even though intense physical labor and a limited food supply kept the Maycoba group thin, the Pimas there might still be genetically susceptible to obesity. In 1995, the scientists hauled a trailer into the mountains to set up a makeshift research station. It's been shuttered now for several years, and locks were rusty when Julian Esparza and Leslie Schulz opened it again last spring, their first visit in more than a decade.

LESLIE SCHULZ: Yeah, it was pretty fancy at the time. [laughs] Now it doesn't look quite so fancy any more.

JULIAN ESPARZA: You see?

LESLIE SCHULZ: Yeah.

VICKI MONKS: Esparza and Schulz are both specialists in the nutritional aspects of diabetes and obesity. Collaborating with other scientists under a grant from NIH, the team ran the same battery of tests here in 1995 that they’d used earlier in Arizona. If the Maycoba Pimas had thrifty genes, the resting metabolic rate should be lower than that of non-Pimas. Eric Ravussin was part of the team.

ERIC RAVUSSIN: And in the same environment, there are people calling themselves "blancos" or "mestizos" who are not Pimas, and they are different genetically, but they live in the same environment. And we're hoping to find a difference between Pima in this environment versus non-Pimas.

VICKI MONKS: But as it turned out, there was no difference. The Maycoba Pimas didn't have thrifty metabolisms. The research team in Mexico now expanded the investigation to include environmental factor, such as diet and physical activity Leslie Schulz turned to doubly labeled water, a technique for measuring energy burned as people carry on their daily lives A research subject drinks a short glass of special water containing heavy isotopes of hydrogen and oxygen that can be tracked as they're gradually eliminated from the body.

LESLIE SCHULZ: It's perfectly safe. It sounds terrible when you say you're giving people this water that has isotopes in it, but they're both stable, and they're perfectly safe to consume.

VICKI MONKS: A few hours after someone drinks the water, researchers collect a urine sample, then wait one week, and collect another. By comparing the ratios of hydrogen to oxygen in the samples, they can calculate precisely how many calories that person burned during the week. The test is expensive, about $500 a glass, and the team found that follow-up in these mountains could be problematic.

LESLIE SCHULZ: It's very important that they are available for that seven day follow-up to give another urine sample. Some time life gets in the way. [laughs] And so if somebody has work to do out in the field, they don't have time to come into the clinic in order to give their urine sample. That's not their biggest priority in the day.

VICKI MONKS: More than once, the researchers climbed through the mountains to do their follow-ups. Esparza lived among the Maycoba Pimas for two years during the study. His rapport with the community set this study apart from other research involving Native Americans. It's a common complaint that scientists focus so much on the science, they ignore the people themselves.

JULIAN ESPARZA: I grew up in the kind of community like that, so that was like my home. So I think it was one of the key to have good relations with this community. If we have this good relations with the people, I think we have the best real information.

VICKI MONKS: The doubly labeled water study provided critical data on energy expenditure. Leslie Schulz said the Arizona Pimas burn just as many calories each day as those in Mexico.

LESLIE SCHULZ: The heavier a person is, the more energy it takes to do everything, because you're moving more mass through distance. When we look at the total energy expenditure, if you just look at the total levels, they're not that different, because the Arizona Pimas are considerably heavier. However, if you make that adjustment for their body weight, you find that the total energy expenditure in Mexico is much greater than it is in the Arizona Pimas, and it's definitely an indication of the lifestyle.

VICKI MONKS: So the intense physical activity in Mexico seems to protect Pimas there from developing obesity, and there's one other crucial difference.

CLIFTON BOGARDUS: The difference between people who weigh a lot and people who don't weigh a lot is the people who weigh a lot eat a lot.

VICKI MONKS: Clifton Bogardus is chief of the NIH clinical research branch in Phoenix. He believes that genetic signals are involved in the desire for food.

CLIFTON BOGARDUS: So it's not because they're slovenly, gluttonous individuals. They just have a genetic drive to eat more. The question is, "Why? Why do they eat more?" And I don't think we have a good answer for very many people. I mean, there's a few genetic mutations that cause overeating and obesity in humans, but they account for 5% of the overweight people in the world and no more than that.

VICKI MONKS: The researchers began looking at hormones that control appetite. The hormone leptin, for example, suppresses appetite in animal studies. So in theory, a person with high leptin levels would be satisfied with less food. A person with low leptin levels would eat more. If Pima Indians did have thrifty genes to help them put on fat quickly, they'd most likely have lower leptin concentrations than non-Pimas.

ERIC RAVUSSIN: Once again, we could not say that leptin was the problem.

VICKI MONKS: Eric Ravussin.

ERIC RAVUSSIN: We found that the leptin concentration in Pimas in Maycoba was totally normal compared to the non-Pimas. And, you know, this is frustrating, because we have been trying to find these signals, which confer so much susceptibility.

VICKI MONKS: In the 40 some odd years that they've been studying the Pima, scientists haven't found quite what they're looking for. Pimas don't have genetically slower metabolisms, and they don't have genetically lower hormone levels. Given the sum of these results, is it possible to identify any thrifty genes? Do thrifty genes even exist? Clifton Bogardus.

CLIFTON BOGARDUS: No and no. So it's a very nice theory, but I don't think anyone has found such a thing in a human as yet.

VICKI MONKS: So the thrifty gene was out, but the leptin studies uncovered something else. After adjusting their results for body weight, the researchers discovered that the Maycoba Pimas were actually producing more leptin than genetically similar Arizona Pimas. The finding was a revelation. Somehow something in the Maycoba environment appears to ratchet up leptin production or something in the Arizona environment ratchets it down. Whatever the case, the Maycoba Pima seem to be getting signals earlier to stop eating.

LESLIE SCHULZ: Then when can we learn from that, that's in their environment that's making that difference, that could then potentially cause people to be leaner?

VICKI MONKS: Corn is the staple in Maycoba, along with beans, squash, potatoes, greens, and peaches. The diet contains lots of fiber and healthy nutrients. The leptin studies point to the possibility that this diet or physical activity or both may be influencing gene expression in ways that aren't yet understood.

When we find Maria Luisa Lao Rodriguez, she's washing clothes at a mountain stream, rubbing them with a coarse soap, slapping them on a flat rock.

VICKI MONKS: Trabajo, mucho trabajo. It's a lot of work. Duro. Your work is hard.

MARIA LUISA LAO RODRIQUEZ: Pues, ni modo. Tengo que trabajar duro.Well, whatever, I have to work hard.

VICKI MONKS: Maria's neighbor, 75-year-old Egriselda Coronado Galviz, is hauling water from the spring up the hillside to her home. It's a twice daily chore.

EGRISELDA CORONADO GALAVIZ: Descánsate, pues,esta muy pesado It's really heavy. Let's take a rest.

VICKI MONKS: Whether it's the diet or the grueling work, something in Maycoba seems to play a role in preventing obesity and diabetes. Scientists don't know what it is or how it works, but they suspect that these environmental influences exert their most profound effects in the very earliest stages of life. Twenty years ago on the Pima reservations in Arizona, scientists observed that babies of diabetic mothers were far more likely than other children to become obese. In fact, other studies confirmed that these children are 10 times as likely to be overweight by the time they're 7 years old, and at much greater risk of developing diabetes later on. Eric Ravussin says it's not a matter of simple genetic inheritance.

ERIC RAVISSUN: It's been very well shown by the studies in Pima Indians that if you have diabetes during pregnancy, the impact on the fetus is to provide some excess susceptibility to diabetes, totally independent of your coding DNA

VICKI MONKS: The search to discover why this happens may just unlock some of the mysteries behind the escalating worldwide epidemics of diabetes and obesity.

JOHN HOCKENBERRY: What happened to the Arizona Pima? Obesity rates now exceed 70% among the Pima, and more than three-quarters of older Pima adults have diabetes, and the rest of us may be following in their footsteps. From the science section to the late night infomercials, the drumbeat is relentless. Americans are getting fat, fat, fat. Something is changing our relationship to food at a fundamental level, but the change is happening too fast to be in our genes. So what is it?

RANDY JIRTLE: It's not subtle. One is blond, and the other animal it’s brown.

JOHN HOCKENBERRY: In 2000, Duke University researcher Randy Jirtle performed a landmark experiment with a special little mouse called the Viable Yellow Agouti, abbreviated AVY or “Avy.” Avy mice have been inbred for generations until they are as alike genetically as clones or identical twins. [laughs] Yet some are brown and some are yellow.

RANDY JIRTLE: Now, why this is so very important is that these yellow mice, as they grow, they become obese, they get diabetes, and they get cancer.

JOHN HOCKENBERRY: But when Jirtle fed these yellow mice a special diet during pregnancy, their offspring grew up svelte, brown, and healthy, instead of obese, yellow, and diabetic. The change to brown, Jirtle showed, was caused by a chemical process called "methylation," in which a quartet of carbon and hydrogen atoms called a "methyl group" attaches itself to a spot on the mouse's DNA and blocks the gene for yellow coat color, the Agouti gene. The gene can turn on only in the right place at the right time, making a protein that adds a touch of yellow to the hair. But without that methyl group, the Agouti gene turns wildly overactive, and the mice turn really yellow.

RANDY JIRTLE: Animals that are yellow produce that Agouti protein continuously throughout the body. That's what gives rise to the yellow coat color, but it also is produced inappropriately in the brain, and it blocks a receptor in the brain that's involved with the mouse's ability to determine whether or not it's full. And as a consequence, these animals don't perceive that they're ever full, and they eat themselves into obesity. They're always hungry.

JOHN HOCKENBERRY: But a diet rich in methyl donors shuts down the overactive gene. Here's how it works. Methylation occurs throughout the genomes of multicellular organisms. Think of it as tiny methyl groups clinging to the DNA like charms on a charm bracelet. It's one of a family of so-called epigenetic mechanisms, most of them still poorly understood, that actually tell the genome when, where, and how to work. They're kind of like programs on a computer. They're an intrinsic part of the genetic machinery of the cell.

RANDY JIRTLE: Because you've got to remember, every cell in our body has exactly the same genetic information, but yet we have skin cells, liver cells, eye cells. So how does this happen? It's done through programming differences. There are genes that are turned on and other ones that are turned off, and as a consequence, that repertoire of expressed genes varies from cell to cell. That is done through epigenetic changes.

JOHN HOCKENBERRY: Jirtle had shown that an environmental factor, maternal diet, can reprogram this epigenetic machinery in Avy mice, and there may be a bigger revolution in store. Dr. David Martin is a senior research scientist at Children's Hospital in Oakland, California.

DR. DAVID MARTIN: We were working with what we call "transgenic mice," which are mice that have had exogenous pieces of DNA -- pieces of DNA that have been constructed in the lab, inserted into their genomes in a sort of random fashion.

JOHN HOCKENBERRY: Martin's transgenic mice produced unusual red blood cells. You could spot the difference in a microscope. But over several generations, the transgene that produced this effect stopped working in some of the mice, although they were genetically identical. When they mated these mice with mice from a different strain, the gene turned back on. It had been there, silent all along.

DR. DAVID MARTIN: What that study demonstrated was that a piece of the genome could undergo epigenetic silencing in the germ cells, and that that silencing could be stable for generations, but then be reversed.

JOHN HOCKENBERRY: So an epigenetic state, an acquired trait could be inherited. Scientists searching the genome for the keys to disease susceptibility are now recognizing the power of the environment to alter the epigenome. Some common diseases may have their roots in epigenetic changes caused by the environment in the womb. Randy Jirtle.

RANDY JIRTLE: Many of our chronic diseases -- for example, diabetes, cardiovascular disease, cancer, obesity, etc. develop not really in adulthood, but the susceptibility to getting these problems were established at the very earliest stages of development. But, see, nobody really knew what was the link, the memory that would allow something that occurred very early in development to result in these amazingly devastating chronic diseases in adulthood. What we showed is that link is epigenetic changes.

JOHN HOCKENBERRY: Researchers have now reported that diet, pollution, and even maternal nurturing can cause epigenetic changes in mice. But mice and humans may have very different epigenetic programs, says Randy Jirtle, and David Martin counsels caution.

DR. DAVID MARTIN: We do have evidence that epigenetic states can be passed on from one generation to the next, but that evidence is very sketchy, and I think it's very important when dealing with an issue like this to make sure that one does have the evidence.

JOHN HOCKENBERRY: Coming up next on The DNA Files, genes, the environment, and the frightening incidence of asthma. I'm John Hockenberry. We'll be back in a minute.

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JOHN HOCKENBERRY: Welcome back. I'm John Hockenberry. A century ago, asthma was a rarity. Today, it's a scourge for 300 million people around the world, most of whom live in western countries, where asthma has become the most common chronic disease of childhood. The obvious suspect is our man-made environment, but asthma is a heritable disorder, involving dozens of genes, some connected to the lungs, some connected to the immune system, and that all vary from person to person. Scientists need a map of that underlying genetic variation to have any hope of pinning down the scope and action of the environmental causes of asthma In 1992, scientists began a massive study in about a dozen Southern California communities, examining the effects of air pollution and other environmental exposures on the respiratory health of children. But more recently, they have been trying to understand how genetic makeup and environmental factors interact, as producer John Kalish reports.

JOHN KALISH: Seth and Karena Hamilton live with their two kids in a middle class section of Long Beach, known as Belmont Heights. Mom, Dad, and their son all have asthma.

RICHARD HAMILTON: My name is Richard Hamilton.

JOHN KALISH: And how old are you?

RICHARD HAMILTON: Five.

JOHN KALISH: You got any animals in your house?

RICHARD HAMILTON: My doggie.

JOHN KALISH: Named?

RICHARD HAMILTON: Bell.

KARENA HAMILTON: Why can't we have a kitty?

RICHARD HAMILTON: Because we don't want a kitty.

SETH HAMILTON: Are you allergies to kitties?

RICHARD HAMILTON: Yes.

SETH HAMILTON: And do those make your asthma worse?

RICHARD HAMILTON: Yes.

JOHN KALISH: Asthma began at different times in the Hamilton family. Karena, the mom, has had it her whole life, as did her mother. Karena's sister and niece also suffer from asthma, and son, Ricky has had it most of his young life. Her husband, Seth, however, didn't develop asthma until the family moved to Long Beach.
SETH HAMILTON: The doctor said, "You've got it really bad, and it isn't going away, and you're going to be stuck with this now."

KARENA HAMILTON: For him, it was kind of annoying to be having to take these medicines.

SETH HAMILTON: Yeah.

KARENA HAMILTON: To me, it's just old hat. I've been taking them all my life, at least some form of them, and I've just said, "Welcome to the club, honey."

SETH HAMILTON: Yeah.

KARENA HAMILTON: Now you know what the kids and I feel like.

JOHN KALISH: With so many cases of asthma in their family, the Hamiltons are inclined to believe that heredity plays a role, but they also realize that air pollution in Southern California may have caused Seth's asthma, and may be making asthma worse for Karena and Ricky.

KARENA HAMILTON: I've often thought, "Should we be here?"

SETH HAMILTON: Is there somewhere better that we can live or are we just in L.A., and L.A.'s got polluted air, because there's too many cars and too much industry, and where would we go? I don't know.

DR. FRANK GILLILAND: There's been a number of studies trying to identify genes involved that might explain this inheritance in families.

JOHN KALISH: Dr. Frank Gilliland is a professor of preventive medicine at the University of Southern California.

DR. FRANK GILLILAND: But we know that you can't just focus on the genes. You have to think about the combinations of the genes and the environmental exposures together. If we just think of the environment and we just think of the genes, then we're not going to make very much progress.

JOHN KALISH: Gilliland and his colleagues at USC and UCLA are a part of the Southern California Environmental Health Sciences Center. Since 1992, Gilliland has been studying the respiratory health of thousands of Southern California school children. This children's health study has focused on how air pollution affects kids. Not only does Southern California have some of the most polluted air in the nation, but the City of Long Beach has some of the worst pollution in the region. Scientists and public officials say the asthma rate in Long Beach is double that of the rest of California.

The source of most of the pollution is the Port of Long Beach, the second largest port in America. Art Wong with the Long Beach Harbor Department stands on a pier, watching a 15 story high crane pluck containers from a giant ship, and place them on the beds of waiting tractor trucks.

ART WONG: Each year, about 100 billion dollars worth of products are shipped through here, and that's clothing, toys, furniture, TVs, everything you can think of in a shopping mall or a Home Depot has probably come through here.

JOHN KALISH: Fueled by increasing global trade, the volume of ship traffic here is expected to triple in the next 15 to 20 years. For the people who live in this busy port city, that will mean a lot more exhaust in the air from the ships. Many of these giant vessels burn bunker fuel -- a low grade form of diesel. Just one of these ships emits the same amount of air pollution as 12,000 cars. Diesel burning trucks and freight trains then haul the containers on to local freeways or nearby rail yards, passing through residential areas of Long Beach.

The Hudson School on the west side of Long Beach serves grades K through 8. It's on a suburban street lined with beautiful violet Jacaranda trees, but the rear of the school faces the terminal freeway, where some 3,000 trucks a day, most heading to or from the local piers, drive by spewing diesel exhaust. Researchers say data indicates that truck exhaust pushes the asthma rate up in Long Beach.

In early 2007, local parents used air monitoring equipment, provided by the Southern California Environmental Heath Sciences Center and found high levels of particulate matter, both inside and outside the school. Particulates are tiny, solid, or liquid particles of diesel exhaust that can get stuck in the lungs, triggering asthma attacks. Suzanne Arnold is a nurse at the Hudson School.

SUZANNE ARNOLD: Trucks are literally 20 feet from the chain link fence at the back of the playground where the children are playing. There have been a number of occasions when I've had to go out to the field with my wheelchair, and bring a child back to the office, or take an inhaler to them, and wheel them back into the office. That usually happens when the weather is warmer, and when they've been running. That's usually when I have that kind of a problem.

JOHN KALISH: Nurse Arnold says that protecting the health of kids in her school made it necessary for her to speak out against a proposed rail facility across the freeway from the school. That rail yard would bring even more trucks and trains into the area. But there's no simple relationship between asthma and air pollution. Even at the Hudson School, not every child will develop asthma. Yes, pollutants can bring on an asthma attack, but so can emotional stress, mold, and cold air. Professor Gilliland and USC biostatistican Jim Gauderman have been studying a number of genes and genetic variations that are thought to make people either susceptible or resistant to pollutants. For example, one gene called GSTM1 helps the body rid itself of toxins that enter through the lungs. Jim Gauderman.

JIM GAUDERMAN: GSTM1 is what I think of as a garbage truck gene. It goes around and tries to clean up the garbage, meaning things like external environmental toxins, and people that have the null genotype don't have that garbage truck to go around and pick up those kinds of toxins.

JOHN KALISH: 40 to 50% of the people in the world are this null genotype, meaning they don't have a working GSTM1 gene. A study led by Dr. Frank Gilliland found that kids who don't have the GSTM1 gene are at greatest risk for developing asthma, if they're exposed to certain environmental toxins, even in the womb.

DR. FRANK GILLILAND: If you're missing this gene, then if you're exposed to, say, an allergen you're allergic to and an environmental exposure like diesel exhaust, your responses are 20 fold higher than if you had this gene. We don't really understand all the different mechanistic basis for why this gene is so important, and we're frankly surprised by it, but there's lots of work being done on trying to understand that better.

JOHN KALISH: That work is complicated by the fact that GSTM1 is just one of roughly 20 known genes that seem to work together and have strong ties to asthma in multiple populations. Many more genes, perhaps 30 to 50, seem to chime in for different people at different times.

DONATA VERCELLI: Is there anything such as an asthma gene? The gene that is going to explain asthma? The answer is no, I think. That leaves us with a constellation of genes.

JOHN KALISH: Donata Vercelli is assistant director of the Arizona Respiratory Center at the University of Arizona. Not only is asthma genetically complex, says Vercelli, it clearly shows evidence of the epigenetic effects -- genes that work differently based on the environment.

DONATA VERCELLI: What we see is that a certain gene can be associated with less asthma in a certain environment, with more asthma in another environment, and with no effect in yet another environment I think that it is only epigenetics that make it possible for the same gene to do the opposite thing.

JOHN KALISH: It is exactly this astonishing ability of the environment to change the way our DNA works, says Vercelli, that makes it essential to identify the responsible environmental factors.

DONATA VERCELLI: Because we can't change the genes, but we can act on the environment.

JOHN KALISH: Dr. Gilliland says genetic and environmental science will have an important role to play in the development of public policies to curb the kind of air pollution that affects kids at the Hudson School.

DR. FRANK GILLILAND: Right now, there really are no regulations that are directed towards being exposed to proximity to busy roadways or freeways. You can imagine -- it's a whole other level of regulatory approach that would be needed in terms of long term land use planning and school site-ing and other things that need to be considered to be able to address this potential threat to children and asthma in particular.

JOHN KALISH: In the meantime, work continues at the Southern California Environmental Health Sciences Center to develop a better understanding of how the genetic and environmental underpinnings of asthma work. Using genetic samples from thousands of Southern California school children, Gilliland and Gauderman hope to identify what they suspect are tens or maybe even hundreds of genetic variations that play a role in asthma. For The DNA Files, I'm John Kalish.

JOHN HOCKENBERRY: Once upon a time, scientists racing to sequence the human genome believed they would soon have the map to disease susceptibility. [laughs] Now we know that a complex regulatory system of epigenetic mechanisms, the egigenome, can alter and even reverse gene function in different environments. Scientists suddenly find themselves, like eager cave explorers, back facing a baffling network of dark passages, uncertain of which way to proceed.

But the Pima Indians don't have the luxury to wait around. For health reasons, they need to act. And while the epigenetics of complex diseases like asthma and obesity remain obscure, some of the environmental components are coming into clearer view. As Vicki Monks tells us, this is the challenge for the Pima. What to do right now?

VICKI MONKS: In the cool of a light spring desert evening, Rose Martin and Terrol Dew Johnson are picking buds from the cholla cactus. The buds are unopened cactus flowers, one of the desert plants that Pima Indians relied on for centuries. Scientists now understand that cholla buds and other desert foods actually slow down the release of sugars into the bloodstream. They're the perfect foods for preventing diabetes.

Karen Blaine is sauteing cholla buds with olive oil, onions, and garlic, a cooking demonstration.

KAREN BLAINE: We use it in salads. A really great thing about cholla is that it's very high in calcium. One tablespoon is equal to an eight ounce glass of milk.

VICKI MONKS: It's one of the strategies TOCA -- Tohono O'odman Community Action -- is using to promote dietary changes. Cooking lessons will only go so far though, if the foods aren't available. So, TOCA's taking on that mission, too. TOCA's co-director, Tristan Reader, is checking the old irrigation pumps watering farmland on a remote stretch of the reservation where TOCA's growing traditional crops -- corn, squash, watermelon, and tepary beans.

TRISTAN READER: If you tell someone, "You need to eat these foods," but they can't go to the grocery store and buy them. They no longer farm, they're not available anywhere, then all the choices in the world make no sense.

VICKI MONKS: So TOCA's raising traditional food crops on a commercial scale. The effort could go a long way in improving health here, but projects like this don't get much government support. Pima Indians in Arizona have cooperated with government scientists for decades, and all the while diabetes and obesity rates were escalating. Reader believes that the Pimas would be better off if just a fraction of the millions spent on genetic research could have gone to helping people lead healthier lives.

TRISTAN READER: There's a real sense that research has made Native peoples the subjects of the research, but never the beneficiaries, that they've never really been partners. It says, "There's something wrong with you fundamentally, genetically, and it's hopeless, unless the scientists find an answer." What we're saying is, "No, you do have the capacity to choose what you eat, to engage in traditional games and traditional dancing and other forms of physical fitness. You do have that power within yourself, within your family, within your village, within your community to really make changes.

ERIC RAVUSSIN: I think that if I was Pima, I would be very disappointed, too.

VICKI MONKS: Eric Ravussin.

ERIC RAVUSSIN: Because these people have provided help to the scientific community for almost 40 years now, and they have more obesity, they have more Type 2 diabetes. But the thing that we don't know, without these studies, without the careful checking of the population, it would be even worse.

VICKI MONKS: Pima Indians are faced with trying to reverse the effects from 75 years of escalating health problems, brought on by abrupt drastic changes in lifestyle. They can't roll back history and return to completely traditional ways. They live in the modern world. Going back to a subsistence lifestyle plowing with mules isn't the answer. But reestablishing healthy food choices and other traditions could help. From what we know now about epigenetics, intervention is most crucial during key points of development, such as during pregnancy as the fetus develops. And that's the part of this epigenetic research that holds promise for the Pimas. Knowing this much, it's possible to do something, even before all of the science is fully understood. From the Tohono O'odham reservation, I'm Vicki Monks.

JOHN HOCKENBERRY: So we return to the question with which we began. Why do some people get sick while others remain healthy in the same environment? Could it be that large parts of our modern lives -- the food we eat, the air we breathe, the uncounted details of life in our all enveloping manmade world have become an accidental epigenetic experiment. Are we rewriting heredity by inadvertently tinkering with the software that controls our genes or our children's genes? As scientists grope their way towards a new paradigm of gene /environment interaction, we must all take another look at how we choose to live, for what we eat, drink, breathe, how we work and play may exact a personal toll, not only on us, but on our children and their children to come. I'm John Hockenberry. Thanks for listening to The DNA Files.

To find out more about genes and environment, visit our website at dnafiles.org where you can download a podcast of this program. This series, The DNA Files, was produced by SoundVision Productions with funding by the National Science Foundation, U.S. Department of Energy, National Institutes of Health, and the Alfred P. Sloan Foundation. This program, "Rewriting Heredity: Environment and the Genome" was produced by John Rieger, Jon Kalish, and Vicki Monks. The DNA Files is managing editor, Loretta Williams, editor, Deborah George, science content editor, Sally Lehrman. Research director is Adi Gevins. Production support by Noah Miller, Julie Caine, and Liza Graffeo. Office support provided by Steve Nuñez and Beverly Fitzgerald. Our web director is Ginna Allison. Technical engineer and music director is Robin Wise. Our host is John Hockenberry. Our theme music was composed and performed by Steve White. Additional music by Steve White, Conrad Praetzel and Robert Powell. Marketing of The DNA Files is by Schardt Media. Legal services by Cooper, White and Cooper and Spencer Weisbroth. Special thanks to Murray Street Productions. Send your responses and letters to feedback@dnafiles.org. For CDs and transcripts, call 888-303-0022. That's 888-303-0022. The executive producer is Bari Scott. This has been a SoundVision production, distributed by NPR, National Public Radio.

The DNA Files:
Unraveling the Mysteries of Genetics

As heard on National Public Radio

Beyond Human

Hosted by John Hockenberry

Transcript

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and the Alfred P. Sloan Foundation.
JOHN HOCKENBERRY: This is The DNA Files. I'm John Hockenberry. What does it mean to be human? Philosophers have asked that question for hundreds of years. Now scientists consider the question by comparing the DNA of humans to other species.

SEAN CARROLL: The more you look at the genetics, the less unique we are. You know, we don't even have more genes than a puffer fish. So you know, you're just going to have to get over that.

JOHN HOCKENBERRY: We share most of our DNA with chimps, a lot with mice, and even a good bit with animals that seem quite remote like sea urchins and sea slugs.

ROSS HARDISON: There's no reason to think that every nucleotide or every base pair in the human genome is important in making you human. It is possible, maybe way more than half of the DNA in our genomes is doing nothing.

JOHN HOCKENBERRY: Coming up in this hour of The DNA Files, "Beyond Human." We'll be right back after the news.
...
JOHN HOCKENBERRY: All right. Let's talk for a minute about gorillas and chimpanzees. How different do you think they are from us? How different do they seem?

GIRL 1: This sounds kind of cheesy, but when we were at the gorilla exhibit, and the little baby gorilla looked you right in the eye, you could just tell that they were making connections with you, and that you were similar to them, really like making judgments about you.

JOHN HOCKENBERRY: This is The DNA Files. I'm John Hockenberry, and this program is "Beyond Human."

GIRL 2: I guess we're more advanced, like our world, but I doubt a lot of us would be able to survive in the wild, how they do.

JOHN HOCKENBERRY: About 10 feet away, there's a family of Western Lowland gorillas walking through the woods. Well, 10 feet plus some pretty thick glass that we're looking through. Welcome to the world famous Bronx Zoo in New York. I'm here with some 8th graders from Owego, New York in the Congo Gorilla Forest.

GIRL 3: There's a lot of similarities that you can see, but there's also a lot of differences, just structural, like their brain case is smaller.

JOHN HOCKENBERRY: Half a century ago, biologists compared species by looking at body parts and brain size, behavior. Now we have something else to look at, the entire DNA sequence inside our cells, our genomes that help make us us and chimps chimps, aardvarks aardvarks, and algae algae.

JOHN HOCKENBERRY: What percentage of similarity do you think, just guessing between chimps and humans, if you're looking at DNA?

GIRL 4: Probably like 80 or 90?

JOHN HOCKENBERRY: 80 or 90? So that would be like a 10% difference?

GIRL 4: Yeah.

JOHN HOCKENBERRY: What do you think?

GIRL 5: 75, 80%.

JOHN HOCKENBERRY: 75, 80%? Do you know what it really is? Are you ready? Are you sitting down? [laughter]

GIRL 6: Yes, we are sitting down.

JOHN HOCKENBERRY: 99%.

GIRLS: Oh, my gosh. I would have never guessed.

JOHN HOCKENBERRY: I mean, probably there are people in your class that you don't even think are 99% similar to you, right? [laughter] Ooh, touched a nerve.

GIRL 8: Ouch.

JOHN HOCKENBERRY: Okay. Thanks. We'll go down to this end of the table now.

ROSS HARDISON: We have a wonderful resource of many, many new genome sequences that are being determined. Of course, the sequence of the human genome was a revolutionary event for our field.

JOHN HOCKENBERRY: Comparative genomics is a relatively new science. Researchers line up and compare the genetic sequences of different species.

ROSS HARDISON: For comparisons, you need at least two, but we are putting together with our collaborators our alignments among 28 different vertebrate species -- that'd be human and mouse, chimpanzee and macaque and other monkeys --

JOHN HOCKENBERRY: Ross Hardison is director of the Center for Comparative Genomics at Penn State University. The Center analyzes patterns in genomes that contain millions, sometimes billions of bits of information.

ROSS HARDISON: The dog genome is in very good shape, and has been a spectacular resource for study. The cat genome is catching up, and the horse is quite similar to the human genome. We can move over to another continent, Africa, the elephant sequence --

JOHN HOCKENBERRY: As they compare these genomes, scientists are finding subtle differences and surprising similarities in everything from birds to baboons to bacteria.

ROSS HARDISON: And then happily, we're getting several other vertebrate species that are great for certain types of comparisons. Chicken has been published for about two years now. I see a lizard that's coming along that's going to be very useful, and frog -- the frog genome sequence is available, and I think five different fish.

SEAN CARROLL: So we can decode a bacterium. We can decode a virus. We can decode a -- a redwood. We can decode a human using all the same genetic code, and that's just terrific.

JOHN HOCKENBERRY: In the next hour, we'll cross the country visiting the labs and people who are pioneering this new way to look at ancient patterns in DNA. Sean Carroll is a molecular biologist at the University of Wisconsin in Madison.

SEAN CARROLL: So comparative genomics. What do we see when we gaze into genomes, and especially about evolution?

JOHN HOCKENBERRY: Carroll studies how various species evolved to have particular shapes, and what DNA can tell us about how that happened. He's the author of popular books, Endless Forms, Most Beautiful and the Making of the Fittest.

SEAN CARROLL: So the genome is the complete DNA information of an individual, and in us, it contains about three billion bits of individual pieces of information. And what scientists are able to do now is inventory all that information for an individual species. Now this DNA record can tell us about species relationships. It can tell us about how species are different from their ancestors, and of course, it also tells us about the operating instructions for making new individuals. So the DNA record is written in a very simple alphabet, that of just four letters, A, C, G, and T, but it's almost the infinite permutations of those four letters that gives us all the complexity of the living world.

ROSS HARDISON: If you can imagine three billion characters -- and there are only four types of characters -- A, G, C, and T -- and it's the order that they are along these three billion positions that's important.

JOHN HOCKENBERRY: Again, Ross Hardison of Penn State's Center for Comparative Genomics.

ROSS HARDISON: If you line up the genomes of two species, and you find segments that are still quite similar, we say they are conserved. It's an inference that we're drawing.

JOHN HOCKENBERRY: These conserved DNA segments give us a glimpse into the past we share with other species. Researchers are finding similar DNA sequences doing similar tasks in very dissimilar animals.

ROSS HARDISON: That means that they were the same sequence and the last common ancestor, and they're still similar enough for us to line them up. Almost the entire genome has that property between humans and chimp. You go out to mouse and it's a lot less. So we can line up of the order of -- depending on how you do it, maybe 40%. So you can say that 40% of human is conserved with mouse. Then if you line up human with chicken, it's a very small percent of human that lines up with chicken.

So the fact that something is conserved in human and chimps doesn't mean much. It sure means a lot if you can find it conserved between humans and fish or humans and chickens. And in fact what we see, if we look at thousands of regulatory regions, you see that a small fraction of them, about 2% align all the way from humans out to chickens, and they have some very interesting properties. I mean, not only has selection been working on them really hard, so they don