The DNA Files:
Unraveling the Mysteries of Genetics

As heard on National Public Radio

Minding the Brain

Hosted by John Hockenberry

Transcript

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JOHN HOCKENBERRY: Welcome to The DNA Files. I'm John Hockenberry. Our show today is called, "Minding the Brain," and it's about uh um--it's about, oh, you know, stuff like:

WOMAN: Hello.

MAN: Hi, honey, it's me. I'm just leaving the office now.

WOMAN: Oh, okay, fine. Oh, and don't forget to stop at the grocery store.

MAN: Oh, that's right. Uh what was it that you wanted me to pick up again?

JOHN HOCKENBERRY: Memory, that's it. Memory. Memory, and learning, and the brain.

DAVID GLANZMAN: Memory is a dual edged sword. In other words, we've all had memories that are highly unpleasant, and you don't want just any experience stimulating memory.

PATRICIA CHURCHLAND: I remember when I held a whole human brain in my hands for the very first time, and here was this astonishing machine.

JOHN HOCKENBERRY: Don't drop that brain. We'll be right back after the news.
...

JOHN HOCKENBERRY: This is The DNA Files. I'm John Hockenberry. And today we're going to see what genetics can tell us about memory and learning and the brain, or I could just as well say, memory, learning, and the mind. The mind and the brain are the same thing, right? Or are they?

PAUL CHURCHLAND: I remember wondering as a teenager what thought was, and I remember thinking, "Well, I guess it has to be electricity."

PATRICIA CHURCHLAND: I remember when I held a whole human brain in my hands for the very first time, and here was this astonishing machine

JOHN HOCKENBERRY: Paul and Patricia Churchland are philosophers at the University of California at San Diego. They're kind of unusual for philosophers, because they spend a lot of time studying neuroscience. Sometimes they call themselves "neurophilosophers." Anyway, the question known as "the mind/brain problem" or "the mind/body problem" is an old one. It goes back at least to the 18th century, to the French philosopher, Descartes.

PAUL CHURCHLAND: People didn't really appreciate that the brain was responsible for seeing and hearing and feeling and thinking and so forth until fairly late in human history. Even the Greeks were confused about it. Uh was it uh uh --

PATRICIA CHURCHLAND: Well, Hippocrates --

PAUL CHURCHLAND: Yeah, Hippocrates.

PATRICIA CHURCHLAND: Knew the brain did all those things, but nobody had the slightest idea how this mass of stuff could produce such a thing as perception or thought or regulate sleep. So the mind/body problem as we know it emerged with Descartes. He came to the view that the brain was just a kind of conduit for sensory signals in and motor signals out, and that the soul had to be a nonphysical thing that did the thinking and the deciding. There were really two reasons for thinking that. One, Descartes understood about mechanical devices, and he thought, "The mind is creative, and how could a mechanical device be creative?" The other reason was that he felt there was genuine choice that was uncaused, so that when we made a decision to give alms to the poor, that such a decision would not be caused by any antecedent physical event. And consequently it's really with Descartes that we get this idea that there is the mind, which is nonphysical thing on the one hand, and the body, which is a physical thing on the other hand. Then the problem is: How do they interact?

PAUL CHURCHLAND: [laughs]

PATRICIA CHURCHLAND: And nobody was able to solve the difficulty. And now, of course, we don't think there is a mind/body problem, because we don't think there are two kinds of stuff.

JOHN HOCKENBERRY: The Churchlands say Descartes got it wrong. The mind is entirely caused by the brain. It's the same thing. There's no difference. This does seem like a practical, no nonsense way to solve the problem. All the same, questions come up. For example, if you cut your finger and I say, "I feel your pain," believe me, that's just a courtesy. I don't actually feel a thing. I may empathize with you, because I know what it feels like when I cut my finger, but I have no access to your sensations. In theory, I could check out everything that's going on in your brain when you cut your finger. I could watch the activity of your nerve cells. Your mind though--only you can experience that.

PAUL CHURCHLAND: That's certainly true, but I don't think it's terribly surprising. The parts of my brain that make judgments like "I'm in pain" or "I'm happy" or "I'm afraid" is connected to the rest of my brain in intricate ways that is not connected to yours and similarly for you. So it's no surprise that I should have direct knowledge of my own internal states, and you have a knowledge of your own internal states, and we have to tell one another about them.

JOHN HOCKENBERRY: All right. Let me take another shot. If we are entirely physical creatures, then everything we do or think or feel must have a purely physical cause. Doesn't that mean we're somehow just machines?

PATRICIA CHURCHLAND: No, it doesn't mean that you're just a machine. Simple machines are the model for what we have in mind when we say we're just a machine, like a television set or a desktop computer. We're vastly more complicated than that. A sea slug is a relatively simple machine, but even it's not simple, and we are vastly more intricate than that.

JOHN HOCKENBERRY: The sea slug, that relatively simple machine, is interesting to neuroscientists precisely because it's so simple, but it can learn and remember, and it can tell us something about how we learn and remember.

Near Miami, Florida, out in Biscayne Bay on a little spit of an island, there's a two-story building shaped like a shoe box, more or less the color of the sand all around. If you notice it at all, you might take it for a warehouse or a lumberyard. Yet the sign reads, "National Resource for Aplysia Facility," and if you go in the door, you'll see hundreds and hundreds of fish tanks, like the tanks you might keep tropical fish in at home--tanks just sitting there, bubbling away in the air-conditioned gloom. And in these tanks are odd creatures.

TOM CAPO: To the touch, they're soft, like a piece of liver. There's no real structure to them. So if you pick them up, they tend to flop off each side of your hand. So they're sort of like a pliable ball in your hand.

JOHN HOCKENBERRY: These are Aplysia. Aplysia californica. Sea slugs, yeah. The National Resource for Aplysia Facility funded by the National Institute of Health is a slug farm. Aplysia can get pretty big--two or three pounds if they've been eating plenty of seaweed, but basically you can think of them as ordinary garden slugs with some extra hardware for underwater living.

TOM CAPO: There's two flaps of skin called parapodia, and underneath or between these flaps of parapodia are the gills and the remnants of the shell. They do have a shell. So if you rub it, you can sort of feel something a little stiff. That's the remnant of the shell for Aplysia, and that's the basic animal, except that if you annoy it enough, it will release purple ink and make a mess. But we have plenty of water that we can wash the ink away.

JOHN HOCKENBERRY: Tom Capo, the manager here, says he's shipping out 30,000 Aplysia this year to researchers all over the country. What with growing tons of seaweed to feed them and pumping and cleaning the water from Biscayne Bay, this is a big operation.

TOM CAPO: We're running water 24 hours a day, cooling it 24 hours a day, and we have one person that just takes care of the seaweed. We have another person that takes care of growing the larvae. So when you think of all the pumping and all the people 24/7 that goes into keeping this facility afloat, it's a pretty expensive proposition.

JOHN HOCKENBERRY: Expensive, when you consider the limited interests of the sea slugs.

TOM CAPO: In the laboratory, all they do is eat, sleep, and copulate.

JOHN HOCKENBERRY: What matters to scientist are the nerve cells, the neurons. Aplysia have humongous neurons.

DAVID GLANZMAN: Most neurobiologists , 99% of the time, they'll go for the big neuron. That just makes life easier.

JOHN HOCKENBERRY: David Glanzman studies the neurobiology of learning and memory at the University of California at Los Angeles. The great thing about Aplysia neurons, he says, besides being big, is how they work. They work the same as human neurons.

DAVID GLANZMAN: I wouldn't be working on Aplysia if I didn't believe that on a fundamental level, the cellular and molecular mechanisms of learning and memory in sea snails weren't the same as they are in our brains, and actually I believe that.

JOHN HOCKENBERRY: When we think of evolution, we usually think of the big changes that have happened over a long period of time. Evolution is radical in this way, but it's also conservative. The basic building blocks of biology are used over and over again.

DAVID GLANZMAN: Minds evolved. They evolved, because brains evolved. And our brains evolved out of simpler brains, but the mechanisms on a fundamental cell and molecular level remain the same. When an animal learns something you and I learn something, there are changes in the strength of the connections between neurons and our brain.

JOHN HOCKENBERRY: Okay, let me draw you a picture here. I'm getting a big sheet of paper and some charcoal and yeah, true, neurons are complicated, and I don't draw all that well, but I can make you a stick figure version. It's a cinch. It's like a child's drawing of a tree. You make a long line for the trunk, and then at the top, you sketch in some little lines for the branches, and at the bottom, more lines coming out for the roots. Simple, huh? A child's image of a neuron. The branches up top are called dendrites. Information comes into the neuron through the dendrites. It moves down the trunk, which is called the axon, and exits at the bottom through the roots called axon terminals. So branches, trunk, roots. In through the dendrites, down the axon, out the axon terminals, that's the information flow. Got it?

Now I'm going to draw a second neuron under the first one. Here we go. Dendrites, axon, oh I love that, that’s nice, that’s nice, axon terminals, another stick tree, you see? I've drawn it so the branches, the dendrites of this lower tree are almost, but not quite touching the roots, the axon terminal of the top tree. There's a tiny, little gap between them. The synapse. So if the first neuron, the tree on the top, wants to talk to the second neuron, it will have to send a messenger across this gap. This synapse. The messenger is a specialized chemical called a neurotransmitter. It bubbles out from a root, an axon terminal makes his way across the gap, and it's picked up by dendrites, the branches in the lower tree.

DAVID GLANZMAN: So the way information travels in the brain is that an electrical impulse travels down the axon until it reaches the end of the axon, which we call the axon terminal, and when it does that, it releases a neurotransmitter. The neurotransmitter binds to receptors in the dendrites of the next cell, and then the electrical impulse will travel down the axon to the next neuron, etc., etc., etc.

JOHN HOCKENBERRY: Coming up, we'll find out what goes on when a sea slug learns. We'll be right back.
...
JOHN HOCKENBERRY: Welcome back. You're listening to The DNA Files, and our show today is called "Minding the Brain." We're talking about memory and learning. To acquire a new behavior like riding a bike or playing the kazoo, you need to learn how to do it, and then remember. Now, scientists believe that when we learn and remember something, there are changes in the flow of information between our neurons. The question is: What changes? What exactly are these changes? I warn you, if you ever put this question to a practicing neuroscientist like David Glanzman --

DAVID GLANZMAN: Cyclic AMP when it synthesizes …

JOHN HOCKENBERRY: Make sure you're sitting down.

DAVID GLANZMAN: …causes the activity of a kinease, known as protein kinease A, and protein kinease A can travel from the cytoplasm to the nucleus and phosphorylate CREB, and when CREB is phosphorylated that in term stimulates the process of gene transcription…

JOHN HOCKENBERRY: Talk about complicated. This is really complicated stuff.

DAVID GLANZMAN: Those are very complicated questions. I think of those as the lifetime employment act for neuorscientists, because [laughs] they're so complicated, it's going to take me the rest of my life to figure them out.

JOHN HOCKENBERRY: Fortunately, we can simplify. We can make a child's version of memory, the same way we made stick figures for neurons. In fact, we can do an experiment with Aplysia, a cartoon version of a real experiment. No actual sea slugs will be harmed in this reenactment.

Picture this. Here's our buddy, Aplysia the sea slug meandering around its fish tank in the laboratory. It's having a good day. The seaweed lunch was especially delicious today, and it's happy. Its gill right under the flaps of skin on its back is busy filtering oxygen out of the water. All is well.

But now since we are pretending to be scientists, we are going to give Aplysia a tiny electric shock. Nothing dangerous, you understand, just a wee shock. Hmm, doesn't like that. We know it doesn't like it, because Aplysia pulls in its gill and shuts it down. This is an instinctive reaction to the shock, perfectly natural. When something ugly happens, you batten down the hatches. Of course, after a while, if there's no further unpleasantness, you forget about it. So the gill comes out again, and Aplysia is happy once more. It has learned absolutely nothing.

Next, we're going to do something clever. We're going to give Aplysia a gentle tap--let's say, on the butt. This won't get much of a response, maybe the sea slug equivalent of "Huh?" The tap isn't threatening. The slug doesn't care, unless right after the tap, we give it a shock. If we keep doing things--tap, zap, tap, zap, tap, zap, tap, zap--[clears throat] over and over, our little slug will begin to learn. It will start to associate the tap with the shock that follows. After a while, we can drop the shock. The tap alone will cause the Aplysia to batten the hatches. This is new behavior. Ladies and gentlemen, this is learning. This is memory.

And our question was, you recall, "What's happening in the neurons--in the nerve cells when memory is formed? Since Aplysia has wonderfully large neurons, scientists are able to follow the action while the slug is being tapped and zapped. What do they see?

All right. Let's go back to my stick figure drawing. I drew two neurons, remember? Like trees with branches and roots, one right on top of the other, almost touching. Let's pretend now these are neurons inside Aplysia while our learning experiment is going on. The top tree, the top neuron is coming in from the rear of the slug. The lower tree is going out to the gill. It's telling the gill to retract. So, incoming butt neuron on top, outgoing gill neuron on below. Normally, there wouldn't be much going on between these guys. The tap doesn't mean a lot until Aplysia starts to associate it with the electric shock. Once it does though, the butt neuron figures it better send a message to the gill neuron. Now we have tap on the butt, information running down the butt neuron through the end of the axon, and bingo--a messenger, a neurotransmitter is sent out. The neurotransmitter hotfoots it over to the gill neuron, hooks up with the dendrites there and information continues down that neuron all the way to the gill itself to say, "Yo, gill, danger. Pull in."

The more we repeat our experiment--tap and zap, tap and zap, tap and zap--the more neurotransmitters flow from one neuron to the next. What was once a trickle becomes a flood. The connection between the neurons is getting stronger. The slightest tap to Aplysia will cause it to retract its gill immediately. This is memory at work, and this connection can get even stronger. There may be structural changes. Word may go to the nucleus of the cell in the crown of the tree right under the dendrites to the DNA. "Wake up, it's construction time. We're going to need carpenters, bricklayers, electricians, plumbers," and the DNA swings into action. As scientists say, it expresses itself. And the heavy building begins. You might see new roots, new axon terminals built on to one neuron, new branches, new dendrites built on to another. These are serious physical changes. You end up with more connections and stronger connections between the neurons. This is now good, solid, long-term memory. Aplysia is going to remember that tap on the butt for a long time.

There you have it. Now you know at least in cartoon form what happens in the neurons when we form a memory. You know there's increased flow of neurotransmitters between the nerve cells, and then as we move to long-term memory, genes are expressed to help make structural changes between neurons. Memory is all about strengthening the connection between nerves.

And now that neuroscientists are beginning to understand what goes on in the nerve cells when we form memories, so what? What good does this do, you may wonder. What difference does it make? Well, look at this.

DR. TIM TULLY: We're going in here. So this--this is the outer room that's like the control center. Let me step over there, and I'll just give you a view.

JOHN HOCKENBERRY: This is Dr. Tim Tully at Cold Spring Harbor Laboratory on Long Island. It's kind of Star Trek in here--computers and buzzing wires and solenoid thingies. But what it's all about is fruit flies. You know, those tiny flies that seem to emerge spontaneously from the cantaloupe or the peaches you left on your kitchen table. There are lots and lots of little flies here in little plastic jars. The jars have openings or channels through which scientists can inject odors.

DR. TIM TULLY: One smell is a chemical called octynol that smells kind of like licorice. And the other one is methylcyclohexonol, which smells a little bit like my tennis shoes in July. So flies are first exposed to the smell of licorice, and they're shocked on their feet. A mild shock. It's just--it just makes them feel uncomfortable, and then we pass fresh air through the chamber, and then expose them to my tennis shoes in July without shock, and we do that for 10 pairings. And subsequently, when we give them a choice between licorice and my tennis shoes in July, the flies will run away from licorice.

JOHN HOCKENBERRY: So the flies associate a smell with danger. Like our sea slugs, the flies learn and remember. What's unusual here in Tully's laboratory is that some of these flies are much better than others. They're [laughs] superflies. They learn faster. They remember longer. How is that possible?

DR. TIM TULLY: When we make new structural connections in the brain, it's basically a growth process. When the biochemistry is properly activated, that connection between two neurons grows stronger. So that structural process is a building process, and we found the general contractor, and so as I was saying --

JOHN HOCKENBERRY: The builder.

DR. TIM TULLY: Yeah.

JOHN HOCKENBERRY: The neuronal builder.

DR. TIM TULLY: The master builder, and it's actually called CREB. C-R-E-B. So CREB is the general contractor, and the analogy is good. If you want to build an addition on to your house, you call the general contractor and you say, "Here's the structure I’d like. Go ahead." He says, "Okay, I know how to do this," and he will call the electricians and the foundation guys and the bricklayers and the carpenters, and organize the whole process of building that structure, and then when it's all done, all the subcontractors and the general contractor goes away.

JOHN HOCKENBERRY: So something in the urgency of the experience--smell, shock, smell, shock, smell, shock--triggers something in the genome to say, 'Call CREB."

DR. TIM TULLY: So CREB in technical terms is a protein called the transcription factor, and transcription factors are proteins that regulate the expression of other genes. So as a transcription factor, CREB is controlling the raw materials needed to grow a structure. And back to the contractor analogy, the phone call that you make to the general contractor is the signal from an active neuron on to CREB. So when a neuron is electrically active from an experience, it starts a biochemical signal to CREB, and when CREB gets it, he goes, "Okay, I got it. I know what you want now. I'll call the subcontractor."

JOHN HOCKENBERRY: So the neuron is basically saying, "Whoa, this is pretty heavy duty. I think we need to nail this one down for life."

DR. TIM TULLY: Right.

JOHN HOCKENBERRY: And that's called long term memory.

DR. TIM TULLY: That's right. So we believe that a long term memory resides in that structural change at the connections among neurons, and CREB is a general contractor for that construction process.

JOHN HOCKENBERRY: So what do you do, if you want to improve that? Would you hire more laborers for CREB? You get more CREBs? What do you do?

DR. TIM TULLY: You could do those things. What we happen to find was a drug that had the effect of making the call, the phone call to CREB stronger. Again, if you imagine working out your structure, your addition to your house with a contractor, you're not going to make one phone call. You're going to make several phone calls. You got to convey a lot of information to the general contractor. So it's going to be a few phone calls. And so basically we found small molecules that increased the signal content to CREB.

JOHN HOCKENBERRY: So you created, biochemically, a situation where I want to put a deck in my house. I call up the contractor. They answer on the first ring, and they're on their way over there with the trucks that afternoon.

DR. TIM TULLY: They understood what you wanted. They know down to detail how to do it. Fine, they got it. So we just turn the gain up on CREB, and that means that we got that building process going with less practice.

JOHN HOCKENBERRY: Now, Tully says the CREB amplifying chemical he's found might be available to you and me one of these days. If that happens, who would want it? You can think of unimpeachable reasons to pop a memory pill, for example, to stem the forgetfulness that comes with old age. You can also think of some not so unimpeachable reasons like "I got to memorize this Shakespeare sonnet for English class tomorrow."

DR. TIM TULLY: The objective of spending the millions of dollars that it takes to find drugs of medical usefulness is not to memorize Shakespeare. It's to cure problems that we get with our brain, either because of age or injury or heredity. We can do these things in principle. That's what medicine is all about. One such example is rehabilitation after stroke. So a stroke is a very focal event in the brain that damages the circuitry. And when you rehab after stroke, what you're doing is reactivating the learning and memory and plasticity machinery to rewire the circuitry around the damaged area to regain lost function. And slowly but surely, your brain uses that memory biochemistry to rewire the damaged area, and you get some recovery of function.

JOHN HOCKENBERRY: There are several companies trying to develop a so-called memory pill, and you can imagine there'd be no shortage of buyers. There are a lot of hurtles to making such a drug, but if the FDA ever approved such a pill, that still doesn't mean you couldn't get in a world of trouble with it. Do you remember David Glanzman who studies sea slugs at the University of California at Los Angeles?

DAVID GLANZMAN: Most people's ideas are, "Well, look, I want to remember. So CREB is a good thing. So the more CREB I have, the better off I am." I once had a colleague who came to me and said, "You know, I'm going to go on a trip to Italy, and I wish I could take a drug that would just stimulate CREB in my brain so I could learn Italian in two weeks." And I said, "Well, maybe you'd be able to learn Italian in two weeks, but if anything bad happened to you, you'd never forget it." That's the opposite side of memory, the thing that people don't understand at first, because they're so obsessed with improving their memory, they don't realize that in fact, memory is a dual edged sword. In other words, we've all had memories that are highly unpleasant, and you don't want just any experience stimulating memory.

JOHN HOCKENBERRY: So far, we've been talking about memory at the level of genes inside a neuron, but brains are networks of neurons. Human brains house something like 100 billion neurons. Each one of them can have thousands of connections to other neurons. Pick up a model of the brain. Hold it in your hands. It looks like a mysterious toy with interlocking parts. What do the parts do? How on earth could you figure it out? Well, you may possibly recall from childhood experiments on watches or clocks that one of the most tempting ways to figure out what a part is doing in a machine is to break it. Afterwards, when you see what's stopped working, you may be able to deduce what the part was meant for. In a similar way, over the years, neurobiologists have learned a lot by looking at broken brains. The scientific literature in fact is chock full of stories of folks who've been whacked on the head with a hammer, blown out bits of their brain with a dynamite stick, accidentally plugged themselves with a cross-bow, and so on.

HOWARD EICHENBAUM: I would come in early in the morning. We would sit down. I would introduce myself. I would describe the test we were going to do. We'd spend the next two hours going through these agonizingly slow and tedious tests. Of course, they didn't seem all that tedious to him, since he wasn't able to really track how long and slow all this was taking. But then typically after an hour or two of this, I would take a quick break, come back not two minutes later, and he simply didn't know me, didn't know what we were doing or anything about it, and we had to just start over again from scratch.

JOHN HOCKENBERRY: Howard Eichenbaum, director of the Center for Memory and Brain at Boston University. He's talking about his work with a famous amnesiac, known only by the initials, H.M. H.M.'s amnesia is not the Hollywood cliche where the hero can't remember who he is or beans about his past. H.M. has a grip on all that, and his short term memory is good enough to carry on a conversation with you or finish a crossword puzzle. What he can't do is convert a short term memory into a long term one. He lives in an eternal present.

HOWARD EICHENBAUM: Each day he gets up. He's again unconcerned about his condition. He doesn't act like today's a catastrophe when he looks old in the mirror. He simply proceeds on with the day in the present moment. He can solve a crossword puzzle. He can follow the storyline on a television show. As long as it doesn't tap something he's seen recently, like what he did this morning, he does fine, and he'll proceed through the day like that, and then just go to sleep that night and wake up and start over again. He could be given the same crossword puzzle and solve it as if he'd never seen it before.

JOHN HOCKENBERRY: Every day for H.M. is a new day.

HOWARD EICHENBAUM: That's right. Very much a new day in which he lives in the present.

JOHN HOCKENBERRY: What does he think happened?

HOWARD EICHENBAUM: That's an excellent question. I don't think he thinks about that.

JOHN HOCKENBERRY: So what does go through H.M.'s mind?

SUZANNE CORKIN: Do you know what you did yesterday?

H.M.: No, I don't.

SUZANNE CORKIN: How about this morning?

H.M.: I don't even remember that.

SUZANNE CORKIN: Could you tell me what you had for lunch today?

H.M.: I don't know, to tell you the truth.

JOHN HOCKENBERRY: How did H.M. wind up with such a damaged memory? We'll tell you after the break. You're listening to The DNA Files.

...
JOHN HOCKENBERRY: Welcome back. This is The DNA Files. I'm John Hockenberry. We've just been introduced to H.M., whose amnesia has taught scientists a lot about learning and memory. What happened to him was this: as a child, H.M. suffered from epilepsy. The older he got, the worse it got. Finally, when his seizures became utterly incapacitating, a desperate remedy was conjured up. A surgeon cut out part of H.M.'s brain, including most of a small horseshoe-shaped structure called the hippocampus. The operation was a home run as far as the epilepsy went, but ever since, no new long term memory. Here's H.M. talking with one of the many scientists who worked with him.

SUZANNE CORKIN: What do you do during a typical day?

H.M.: Oh. See, that's tough. What I don't--I don't remember things.

SUZANNE CORKIN: Uh huh. Do you know what you did yesterday?

H.M.: No, I don't.

SUZANNE CORKIN: How about this morning?

H.M.: I don't even remember that.

SUZANNE CORKIN: Could you tell me what you had for lunch today?

H.M.: I don't know, to tell you the truth. I'm not --

SUZANNE CORKIN: What do you think you'll do tomorrow?

H.M.: Whatever is beneficial.

SUZANNE CORKIN: Good answer. Can you tell me what you look like?

H.M.: Well, let's see. I have brown hair.

SUZANNE CORKIN: Uh huh.

H.M.: Dark brown hair.

SUZANNE CORKIN: Any grey hair?

H.M.: I don't know. See, I don't--I don't remember that at all.

JOHN HOCKENBERRY: It turns out H.M.'s defect is only for a special kind of memory, for what's now called declarative memory, as in "I declare I saw you at the movies last week" or "I'm sure I had ham and eggs for breakfast." H.M. is no good at this. But if you ask him to do something with his hands, let's say, trace a pattern with a pencil, he may not do so great the first day, but he does a little better the second, better still the third, and by the fourth day, he's got it down. He's learning. He's remembering, even though as far as his declarative memory is concerned, he's never seen the pattern before. This is a gigantic clue. Howard Eichenbaum says it shows memory is not one simple thing located at one place in the brain.

HOWARD EICHENBAUM: H.M. was the beginning of our understanding that there are multiple forms of memory, that these different forms are supported by different brain systems, and each have different operating characteristics. Each have different brain pathways. That was news to the world at the time. Most scientists thought that memory was just kind of an inherent property of the processing system, of other functions.

JOHN HOCKENBERRY: It existed everywhere in the brain equally was the idea.

HOWARD EICHENBAUM: That's right. It existed everywhere equally.

JOHN HOCKENBERRY: You remove somebody's hippocampus; memory vanishes, and suddenly the thought is, "Maybe memory is more of an appliance."

HOWARD EICHENBAUM: Right, that it was a gadget itself, and even more like a tape recorder in the brain or something like that. You could find the place where memories are stored. That turned out not to be entirely accurate either.

JOHN HOCKENBERRY: The more scientists look, the more different kinds of memory they find, each with its own network of neurons. We mentioned declarative or conscious memory. There's also procedural memory, which you use unconsciously for everyday tasks, like tying your shoes or riding a bicycle, and there's lots of others. The human brain, after all, is the most complex object in the known universe, or so they say. Science is a little flashlight in a great darkness.

Some philosophers believe that the scientists poking around with their little flashlights are never going to be able to see everything. Do you remember Paul and Patricia Churchland, the neurophilosophers we met at the beginning of this program? They were tackling one of the oldest and hardest problems in philosophy--the mind/body problem or mind/brain problem. The Churchlands told us this problem goes away the minute you shine a light on it. They've concluded our thoughts, our minds are entirely caused by our physical brains. They're the same thing. End of story.

But not everybody buys this neat solution. Colin McGinn teaches philosophy at the University of Miami. He agrees with the Churchlands that the mind is caused by the brain, yet he doesn't think that mind and brain are exactly the same. For example, he says, "Think of the Eiffel Tower." Okay. There. Now think of, let's say, a goat. Obviously, the Eiffel Tower is way bigger than a goat, but was your thought of the Eiffel Tower bigger than your thought of the goat? Think it over. Thoughts don't seem to have any size at all. It's as if the mind, unlike the brain, has no spatial dimensions. So does this end the mind/brain debate? Colin McGinn thinks not.

COLIN MCGINN: I think every position that's been staked out historically has quite serious problems, very serious problems, indeed devastating problems. [laughs] So then the question arises: Are we assuming that we can arrive at a solution to this problem where in fact we might not be able to arrive at a solution to it? The brain is responsible for the mind, and yet, it isn't completely reducible to the brain. So what should we say about that?

JOHN HOCKENBERRY: Well, he thinks a good start would be admit the problem looks insoluble.

COLIN MCGINN: It looks like what we got is a kind of miraculous convergence where it just so happens that when one of these subjective things happens in our minds, one of those objective things happens in our brains.

JOHN HOCKENBERRY: So if the problem is insoluble, he says, if it's a mystery, what's wrong with that? We can handle it. Evolution has shaped our brains for survival in the physical world, not for philosophy.

COLIN MCGINN: The brain is an evolved organ. Its functions are not different essentially from the brains of other organisms. In the case of the human species, as an offshoot of our intelligence, we have the ability to do science and mathematics and philosophy. But it can't be true that the brain was designed to solve the problems of the universe. The brain evolved for straightforward, adaptive reasons. Those had nothing to do with plumbing the secrets of the universe. It's not surprising that we don't know something. What's surprising is that we know as much of the universe as we actually do know, given that there's no reason why we should. In physics, even the most basic concepts, we just don't know what matter really is. We don't know what charge really is. We don't know what a field really is. Does anybody know what an electron is in itself? No. If we don't know what matter is in itself anyway, is it so surprising we don't understand how matter can generate minds? But in the end, if it turns out there are mysteries which we can't understand, is that a tragedy? That's just life. [laughs] That's the way it is.

JOHN HOCKENBERRY: Of course, most scientists aren't trying to understand everything. They're happy if they can get a handle on even a little piece of the big picture. Some scientists are finding they can skip the mind/brain question all together, and just look for ways to change the brain by using the mind. Here's an example. Did you ever wonder what--what's going on? Did you ever won--hey, wait a minute. Okay, all right, that's it. Cut it out. All right, then. Are we back? I think we're back. Did you ever wonder what it would be like to live with attention deficit hyperactivity disorder? ADHD, as they call it. Could it be sort of like having somebody changing channels on you all the time?

Susan Smalley at the University of California at Los Angeles says ADHD is actually just a different way of handling memory and attention and stress.

SUSAN SMALLEY: So we're starting to recognize that having a disorder is basically being at an extreme on a normal continuum. For example, I always use height. If you're 7'6 and you're a teenager in high school, that can be rather impairing, but being very tall is just a difference in the population. We recognize that the impairment part arises, because the individual with their particular brain organization and way of responding to the world runs up against a culture or a school system that isn't that accepting of that way of seeing and processing the world. For example, kids and adults with ADHD underestimate time. So they have very different ways of perceiving time. We have a stopwatch, and we time a 15 second time interval, and then say, "How much time elapsed?" An individual with ADHD will perceive that time as shorter than on average an individual without ADHD. There's nothing right or wrong about the way you perceive time, but it does have implications in you being on time.

JOHN HOCKENBERRY: Smalley says people with ADHD may be more sensitive to emotional stress, which gets in the way of their short term memory. They forget where they put their car keys and what a friend just told them. ADHD may be just a different way of processing the world. All the same, Smalley is among the scientists who think the cause is mainly genetic.

SUSAN SMALLEY: Gene studies have led us to identify maybe five to ten percent of the cause of ADHD, but we think genes play maybe 75 percent. So there are many, many genes we have not yet identified.

JOHN HOCKENBERRY: Smalley and her colleagues are busy looking for those missing genes. They expect to find a lot of them before too long, maybe in a couple of years. However, simply having a gene doesn't mean anything by itself. The issue, she says, is whether the gene is turned on or off, whether it's expressed.

SUSAN SMALLEY: There are many environmental factors that can contribute to the expression of genes in the population, and some of the work that we're doing has to do with looking at our own ability to self-regulate our brains, our bodies, and subsequently our gene expression. We're really at the very, very beginning of this field of research, but if you look at a lot of the work that's coming out of mind/body medicine, you'll see that individuals have a much greater capacity to regulate their brain and body biology than we perhaps previously thought.

JOHN HOCKENBERRY: Hmm. Did you catch that? Mind/body medicine. Do you see where we're headed?

MAN: Let us begin. Settle yourself into your chair. Put both feet flat upon the floor and notice all the points of contact. Now let's focus on the breath, drawing the breath in easily through your nose or through your mouth, follow it down through your throat, into your chest, letting your tummy rise slightly, following the breath all the way in.

JOHN HOCKENBERRY: That's right. Meditation. Smalley and others have begun treating ADHD patients with meditation techniques. Some of these patients were taking medicine for ADHD, some weren't. They all said they liked meditating. It made them feel better. The idea, which Smalley hopes to prove in a clinical trial is that meditation will actually change their brains and alter their gene expression.

SUSAN SMALLEY: It's really important to remember that we're not talking about actually changing the structure of our DNA, but rather we're talking about every cell contains the same DNA information, but we know that certain cells express certain genes, and other cells express other genes. There are many factors that contribute to gene expression.

JOHN HOCKENBERRY: Do you remember our experiment with Aplysia where the slug's genes turned on, expressed while it was learning? You could think of that as a gene expression in response to the environment. Stress, cigarette smoking, many things in your environment can alter your brain biochemistry. Indeed, wouldn't any experience that changes your mind change your brain as well?

SUSAN SMALLEY: The future will probably yield much greater insight into how we as an individual will be able to regulate our own gene expression. We just have a little bit of knowledge right now about it, but the future will really help us uncover how much can we regulate our own biology, including our gene expression.

JOHN HOCKENBERRY: How much we can regulate, we might control. This is the Holy Grail in brain science. So much that happens in the brain goes on without our conscious control or intervention, and that's something to be grateful for, really. Imagine having to remind yourself to breathe or to pump your heart every few seconds, but this research seems to open a new door to direct intervention into the brain through influencing gene expression. It makes sense, really. You're trying to regulate your biology every time you decide to exercise or go on a diet, but what if there was a pill for things like memory? Why not a pill for playing the violin? A pill for learning Greek? The point is, the more neuroscientists learn, the more the rest of us can wonder what's next. Sure, there's hype--no, not everything will pan out as a simple pill, a silver bullet, but hey, we can sure wonder, right?

Remember our primitive pals, Aplysia, the sea slugs? No, no, you--you're blanking? How about my name? Do you remember that? No? [laughs] This is The DNA Files. Does that ring a bell? Okay. Who's the president? What's your mother's maiden name? Come on. The color of water, last year's winner on American Idol. Think harder. Let's get those neurons firing.
MAN: I'll get it.

JUNE: Hi.

MAN: Oh, hi, June.

JUNE: I hope I'm not interrupting dinner. I just stopped by to pick up the tickets.

MAN: Uh, tickets?

JUNE: Yeah. Audrey said you had the two spare tickets to the game tonight?

MAN: Oh, no. I had them with me at work, and I left them sitting on my desk. Listen, if I leave now, I can go and pick them up and drive them over to you.

JOHN HOCKENBERRY: There. Is it coming back to you? We now know that forming long term memory involves real physical changes, structural changes in the nerve cells in your brain. So the point is uh --

MRS. WILLIAMS: Yes?

WOMAN: Mrs. Williams, there's a gentleman here to see you from textile products.

MRS. WILLIAMS: Textile products?

WOMAN: Yes, Mr. Graywall.

MRS. WILLIAMS: Graywall? Oh, of course, show him right in, will you? I'd forgotten all about that appointment. I meant to write that down as soon as I got back to the office. Oh, boy.

JOHN HOCKENBERRY: Let's leave Williams and Graywall to their little drama, and I'll leave you with this. If you remember anything about this program a week from now, it will be because I have changed your brain. [laughs] That's right. I changed the chemistry of your brain, but no humans were harmed in the production of this program, as far as we know.

This is The DNA Files. Thanks for listening.
***

To find out more about memory, learning, 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, "Minding the Brain" was produced by Larry Massett. 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 Jenn Jongsma. 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 Larry Massett, 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. Thanks also to Universal Training for the memory training audio and to Suzanne Corkin for the audio of amnesiac, H.M. 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

DNA: The Code of the Wild
Genetics & Applied Ecology

Hosted by John Hockenberry

Transcript

SoundVision Productions
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For further information about genetics and these programs, as well as the producers who brought you this series, visit the project web site at www.dnafiles.org.
Send your questions about genetics and this project to feedback@dnafiles.org.

Funding for this series was made possible by generous grants from The National Science Foundation and the Alfred P. Sloan Foundation.

Last reviewed for accuracy: February 2002.
JOHN HOCKENBERRY: Welcome to The DNA Files. I'm John Hockenberry. From the very first life forms, Nature has been keeping copious notes—keeping track of every function and every relationship an organism has had.
JOHN AVISE: The history of life is basically written in the language of DNA.
MIKE GILPIN: It’s as if animals had just incredibly long Universal Product Codes, that they had all over their skin, dropping off their body.
JO HANDELSMAN: Once you can read the code for an E.coli cell, you can pretty much read the code for any organism, a human, or a giraffe, or anything you want.
JOHN HOCKENBERRY: What we’re learning from the DNA, in organisms as diverse as bears, barnacles, and bacteria, is telling us not only intimate details about these life-forms, but about all of life. DNA is the Code of the Wild. We'll meet the people trying to crack it. All this and more, coming up, when The DNA Files returns…

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JOHN HOCKENBERRY: You’ve heard of transgenic corn and genetically modified monkeys, now here’s something new. In the quest for a perfect lawn, genetic scientists are turning to biotech to create grass that doesn’t grow. Erik Anderson has the story.
BRAD MARTIN: When I first got this house, the front lawn was barely alive and the back was brown and I'm not kidding it was.
ERIK ANDERSON: Brad Martin’s dormant lawn in San Diego has exploded with life since he began his regimen of watering, fertilizing, weeding and mowing…
BRAD MARTIN: I'd say I probably spend six or seven hours a week on my lawn and with a fulltime job taking care of a lawn, it can be overwhelming.
ERIK ANDERSON: And costly, with Americans spending six billion dollars each year on lawn care. There’s also the ecological cost of air pollution from mowing, and pesticide and fertilizer runoff. So what if lawns could be made to use less water and grow slower? Genetic researchers are turning to Arabidopsis, a spindly mustard weed, as their model. Molecular biologists recently identified almost 26-thousand genes in the plant, opening the door to understanding how it grows.
Inside a weatherworn greenhouse at the Salk Institute in La Jolla, California, a large fan cools several trays of the fast-growing weed. The plants in one look different from the rest, as geneticist Joanne Chory points out.
JOANNE CHORY: You can see these plants are a lot smaller. They only stand a few inches high as opposed to 12, 13, 14 inches high. And the rosette leaves are much smaller and the plant is dwarfed in general.
ERIK ANDERSON: Comparing the shorter plants' genes to those in the normal Arabidopsis genome, Chory found a genetic switch that regulates the production of a growth hormone. In normal plants, the switch is programmed to be in the “on” position. When stimulated by sunlight, the hormone encourages stem growth. But Chory found that in the shorter plants the switch is turned “off,” blocking hormone production. By isolating that genetic switch and reproducing it in the lab, she can insert it into one of the normal plants … and its offspring will inherit it too.
JOANNE CHORY: These plants will grow more slowly, stay green, utilize less water because they are growing more slowly and also need a lot less care.
ERIK ANDERSON: … all qualities that appeal to homeowners and golf-course-keepers which represent a potential 10-billion dollar seed market. The world’s largest lawn care company -- Scotts -- is just one of a number of large corporations hoping to turn a profit with genetic gardening.
Inside Greenhouse number three, on Scott’s campus in Marysville, Ohio, scientist Bob Harriman has developed a slow-growing bluegrass. Using Arabidopsis and other plants as his guides, he found a genetic switch in bluegrass that controls growth. Now he’s considering adding other traits, like drought and pesticide resistance. But he needs more pieces of the puzzle before he can get the grass to do what he wants and still remain healthy.
BOB HARRIMAN: Knowing how a single gene is turned on or turned off is less important and has less of an impact on how are all these genes working together at different points in its growth cycle.
ERIK ANDERSON: Developers of these new grasses tout the environmental benefits of less mowing, watering and fertilizing, but not everyone is convinced that genetically altered grasses are a good idea. At a recent biotechnology conference in San Diego, Indiana University Biologist Martha Crouch joined other opponents for a teach-in. She believes the research is moving too quickly.
MARTHA CROUCH: The people who do genetic engineering feel they know a lot because they know the sequence of the gene. But they have no idea what that will do in the environment.
ERIK ANDERSON: Crouch is concerned about ecological domino effects in the environment. By sharing pollen, manufactured grasses might transfer genetically altered traits like slow-growth and pesticide resistance to other nearby grasses.
MARTHA CROUCH: They say we're gonna change this little part of the machine, and we're gonna make it so the grass does this. But when you do that the grass is actually a living organism with a mind of its own and you get unpredictable consequences.
ERIK ANDERSON: So what about regulation? Crops are regulated by three agencies, but only one -- the Department of Agriculture -- monitors genetically modified grass research. Because of concerns about pollen flow, regulators do limit the growth and transportation of test grasses. But there’s no clear plan for agencies to oversee low mow grass seeds once they go on sale. Scotts officials are hoping to bring their product to market several years from now. That’s when homeowners like Brad Martin will decide whether the ecological risk is worth bringing the genetic revolution into their backyards.
BRAD MARTIN: There’s nothing more satisfying, then ah, after you get your lawn cut you take a good shower, and you just go out there and survey your kingdom. (laughs)
For The DNA Files, I’m Erik Anderson.

● ● ●

JOHN HOCKENBERRY: Welcome to The DNA Files. I'm John Hockenberry. Read any good books lately? Here’s something you probably haven’t read. A little difficult to understand, though, only in the past few decades, have we even started to learn what it means.
JOHN AVISE: The history of life is basically written in the language of DNA, and what modern molecular biology has given us are the tools to read that language for the first time. It's just opened up a whole world of possibilities that could hardly have been imagined even twenty or 30 years ago.
MIKE GILPIN: And it's all done with DNA. It’s as if animals had just incredibly long Universal Product Codes, that they had all over their skin, dropping off their body, leaving behind in their feces. And it's made it so much easier to collect information, and make all sorts of inferences about, let's see if this is the population, the daddy must be this animal and things like that. For difficult to observe animals, such as forest elephants, grizzly bears we have a much greater insight into what the population is, what the age structure is, what the genetic relatedness-es are between the animals.
[beeping sounds of Morse code]
JOHN HOCKENBERRY: That's Morse Code. It's kind of an antique, but it's fascinating really. It has only four symbols and you can hear them. There's the dot, dash, short space, long space. Yet, with just these four symbols, you could spell out an entire encyclopedia.
JOHN HOCKENBERRY: Scientists use just four symbols to spell out quite another code, the code for life. A, T, C, G, these are the initials for the four bases of DNA: adenine, thymine, cytosine and guanine. A strand of DNA has millions or billions of these bases, strung together in varying order. And from that order, of A’s, T’s C’s and G’s, we can decipher information, about individual species...
OLIVER RYDER: The closest living ancestor of whales is the hippopotamus.
MIKE GILPIN: And there was a high fraction of grizzlies’ litters of cubs that had two different fathers.
JOHN HOCKENBERRY: And in fact we can decipher things about all species…
JO HANDELSMAN: Now the DNA technologies are so powerful, and have such a wonderful application to ecological and environmental questions, as well as evolutionary questions, and many, many ecologists are using molecular biology, or DNA technology, in their research.
OLIVER RYDER: One thing from studying the genetics of endangered species is the commonality we share. We studied gorillas and some rhinos and some tigers, and they have some of the same kinds of genetic errors that humans do.
ED DELONG: Not only are we all related, in the sense that we had a common ancestor, and we all kind of share the same genetic materials, we're also swapping DNA, that is, collectively amongst organisms, more than we thought we were.
JOHN HOCKENBERRY: Welcome to “DNA, the Code of the Wild,” a look at how genetics and DNA have helped us understand ecology and manage environments.
Game wardens now have a new tool for catching poachers who illegally kill wildlife.
CHARLES SCHWARTZ: DNA is used in a forensic sense to help identify individual bears or species of bears. Law enforcement, for example, can use DNA if they have somebody that’s been identified as poaching grizzly bear, they can then check to see if they can find traces of grizzly bear, either blood or hair, and verify that using DNA.
JOHN HOCKENBERRY: Charles Schwartz is a wildlife biologist at the Northern Rocky Mountain Science Center. He’s seen DNA used to find people that harm animals, and animals that harm people.
CHARLES SCHWARTZ: On a very rare occasion we’ll have a bear that will come into conflict with a human, and injure them. And so those bears are usually removed from the population, they’re trapped and sent to zoos. If there’s no place where they can be put, they’re euthanized. Prior to DNA identification of individuals, basically, if a person had a description of the bear, and if a bear fit that description it was removed. And you may or you may not have the offending individual.
Now, what we have, and there was an example of this in Yellowstone National Park a couple of years ago, there was a bear that was coming into campgrounds and smashing tents. They had a difficult time capturing him, but when they finally did, what they also had was a hair sample from a previous incident. They were able to take both the hair sample that they had and the hair sample from the bear they captured, compare the two and, in fact, confirm that, yes, they had the individual that was causing the problems, and he was then removed from the park and put in a zoo. And so the problem was cleared up and there was no non-offending individual that just happened to be in the wrong place at the right time and get blamed for something that it wasn’t doing.
JOHN HOCKENBERRY: DNA can be used to identify “whodunit,” or who it was done to.
STEVE PALUMBI: We've done a number of different things in marine conservation biology to try to use DNA to come up with answers to questions that otherwise couldn't have been answered.
JOHN HOCKENBERRY: Harvard University Evolutionary Biologist Steve Palumbi.
STEVE PALUMBI: One of the first ones we looked at was what species were really present in the retail market that sell whale meat around the world.
JOHN HOCKENBERRY: The International Whaling Commission banned commercial whaling in 1985. But, for scientific research only, nations can still capture the more-abundant species of Minke whales and those animals can later be sold commercially. So, any whale meat for sale should be only Minke whale. Right?
STEVE PALUMBI: Well the problem is, if you ever go to the retail market in Japan or Korea, once you buy a piece of whale meat, it's a tiny little piece of a very big animal, and all the things that you might need to tell what species of whale it was are gone. But that little piece of meat still has the DNA in it. So we developed a way to go into that market, sample those specimens, and then sequence the DNA to try to find out, one, what the species were and sometimes, where those animals actually came from. But we found humpback whales, and we found fin whales and gray whales and sperm whales, and blue whales, and pilot whales, dolphins, porpoises, a huge number of different species are in this market. And that was quite a surprise to people because it was supposed to be a Minke whale meat market, and it turn out to be much more than that. So the DNA testing has at least the promise to be able to keep the market honest. And by keeping the market honest, that means you can at least try to afford protection to species that really need it, where at the same time allowing the exploitation of species that have been recovering and might be able to be fished at some low level.
JOHN HOCKENBERRY: In the modern biology lab, you can extract DNA from a cell, make copies of it and use, what’s called, restriction enzymes, to grab a specific region of the DNA. Then you can analyze that region, and get computer readouts of the sequence of A’s, T’s, Cs, and G’s. The entire, maybe, billion letter-long sequence of an organism’s DNA is known as its genome. A region of the DNA that codes for a trait is called a gene. Some traits are affected by a combination of genes. But 97% of the DNA is non-coding, it doesn’t code for any trait. We’re not sure what it does. There’s bits of virus DNA stuck in there. There's long sections of repeating sequences which make up about 20 percent of all DNA. We used to call these non-coding sequences “junk DNA.” But in sifting through that junk, we’ve found treasure.
From even the smallest tissue sample, we can extract these repeating sections of DNA and identify not only the species, but also a specific individual, and, sometimes, its whole family.
JOHN AVISE: The beautiful thing, really, about molecular approaches in the studying the tree of life is that one can study branches at any depth in the evolutionary tree, ranging from just the last few thousand years, or even hundreds of years, perhaps, all the way back to some of the deepest branches in the tree of life, which probably separated some 4 billion years ago.
JOHN HOCKENBERRY: John Avise is Professor of Genetics at the University of Georgia. He uses DNA to study evolution.
JOHN AVISE: Every creature is uniquely marked by its DNA. So what we do in my lab is use molecular tools to decipher these genetic marks, and use that information to learn all sorts of things about the behaviors and ecologies and natural histories, and the evolutionary histories of any kind of creature on earth that we'd like to study.
JOHN HOCKENBERRY: Most DNA is in the nucleus of a cell. The exception is in mitochondria, the energy producing part of a cell outside the nucleus. Mitochondria has its own DNA. And mitochondrial DNA is inherited only from the female parent. Mitochondrial DNA is susceptible to changes, mutations, over time. And the children inherit the mother’s mutation. We’re starting to learn the pattern of those mutations, and from that pattern, we can trace an individual’s mother, grandmother, great-grandmother, great-great …
JOHN AVISE: It's sort of like having a phone book or something that mother nature has provided with all the names displayed. And it's just our task then to decipher these names and to use it to reconstruct the female family trees for any kind of creature that we want. And for those of us that are interested in wild life genetics, that was just a tremendous improvement because now we can simply take a little drop of blood or a shed hair or a feather and use that as the basis for our genetic test without having to otherwise disturb the animal or harm it in any way. And quite often the kind of information we gain from these sorts of analyses has immediate relevance to management plans or conservation plans, for example for endangered species.
OLIVER RYDER: The California Condor is the largest bird in North America. It went extinct in the wild; the last birds were removed from the wild in order to prevent the complete extinction of the species. They've been bred in captivity, where their numbers are increasing, and now they've been re-introduced into California and Arizona.
JOHN HOCKENBERRY: Oliver Ryder is the Geneticist for the Center for Reproduction of Endangered Species at the San Diego Zoo. The site of the captive breeding program for condors.
OLIVER RYDER: We've saved DNA from every California Condor. In my refrigerator I have every member of the species, back to the point where they were all brought out of the wild.
JOHN HOCKENBERRY: DNA tests played a big part in the Condor’s re-introduction.
OLIVER RYDER: As a geneticist one of the things I do is try to imagine how genetic sciences can contribute to the conservation effort for endangered species, and the establishment of self-sustaining populations of wildlife, captive and in their native habitat.
Most California Condors alive today can trace their ancestry back to 16 animals. And surely, some of them were related to each other. So, a process of genetic fingerprinting identified that there were basically 3 surviving clans. And that information was used so that the matings of individuals in the same clan were avoided so that inbreeding effects wouldn't reduce the expansion of the population.
Another aspect of the Condors was, if you look at a Condor you can't tell whether it's a male or a female, like many parrots. So a genetic test was used to identify the males and the females. Of course it's very important to make sure that you know the sex of the individuals when you pair them.
JOHN HOCKENBERRY: Okay, so we didn’t save the dodo bird, the passenger pigeon and other extinct species but we might save the Condor. Why should we care? Sure, birds and bears and whales look great on TV nature shows, but is there a reason to protect them, and the thousands of other threatened species? One good reason is biodiversity.
DAVID TILMAN: We are here in the middle of a grassland prairie ecosystem. As I look around I see about 100 species of plants. I know there are about 1000 species of insects, about 5 to 7000 species of bacteria. And large numbers of other kinds of organisms here in this native prairie grassland.
JOHN HOCKENBERRY: David Tilman is Director of the Cedar Creek Natural History Area, and an Ecology professor at the University of Minnesota.
DAVID TILMAN: Ecology is the study of organisms, and the ecosystems in which they evolve and live. An ecosystem refers to all of the organisms that live in a habitat, and to the actual physical habitat itself: the soils, the rainfall pattern, the whole unit of organisms, their physical environment and how they interact.
JOHN HOCKENBERRY: Cedar Creek is a beautiful nine square miles about 30 miles north of Minneapolis. It’s a mosaic of prairie, hardwood and pine forests, cedar swamps, marshland and sedge meadows. On the grounds are dozens of research plots used to study how biodiversity, that is, the variety of species, affects the overall health of an ecosystem.
DAVID TILMAN: Our work focuses on biological diversity. We try to understand why these species co-exist, why there's such phenomenal diversity and what affect that diversity has on how these ecosystems function, their stability, their productivity. We're interested in this, first for fundamental scientific reasons. But also because right now the world is undergoing what appears to be a historically unprecedented, massive extinction event, caused by humans. And we are wondering what effects losing diversity will have on the services that the world's remaining ecosystems can provide to humanity.
JOHN HOCKENBERRY: A study by the International Union for the Conservation of Nature says one quarter of all mammal species and an eighth of all bird species are currently at risk of extinction.
DAVID TILMAN: As we walk through this field, we can look at the incredible diversity of plants, you can see Brown-Eyed Susan, Orange Butterfly Weed There's an ancient plant. This is a Horseweed. These are plant's that were alive back in the time of the dinosaurs basically. There still around with us.
DAVID TILMAN: Organisms, if you will, have a role that allows them to fit in and co-exist with other species, and these differences in roles end up being reflected in differences in their DNA. It's like a more diverse economy. More diverse economies are well known to be more stable. The same is true for more diverse ecosystems. More diverse economies are also often more productive, and that is definitely true in our ecosystems out here. As they have higher diversity, they have greater stability and greater productivity.
JOHN HOCKENBERRY: Remember, biological diversity, or biodiversity, is the variety of different species in an ecosystem. Genetic diversity is the variety of genes within a species. Just as biodiversity contributes to the health of an ecosystem, genetic diversity affects the health of a species. The greater the variety of genes, the more adaptable a species is to changes in the environment, and the less likely a single factor, for instance, genetic or infectious diseases, could wipe out an entire species.
Genetic diversity is a major focus of the U.S. Geological Survey’s Interagency Grizzly Bear Study Team. They provide biological information to policy makers and managers about the population of bears in and around Yellowstone Park.
CHARLES SCHWARTZ: Defining a population is difficult. It's generally a group of animals that are all within a same area.
JOHN HOCKENBERRY: Wildlife biologist Charles Schwartz is the Team Leader.
CHARLES SCHWARTZ: For example we talk about the Greater Yellowstone grizzly bear population. Now, if you go to Glacier National Park, there is a population of bears that live in what's called the Northern Continental Divide Ecosystem. So we have a Northern Continental Divide population of grizzlies; we have a Yellowstone population of grizzlies. The two of them are separated quite a long distance by unoccupied habitat. So you would think of that as two separate populations.
JOHN HOCKENBERRY: That separation means the Yellowstone grizzlies can’t mate with other bear populations. That could cause inbreeding, which could hurt their long-term chances of survival.
CHARLES SCHWARTZ: Historically, grizzly bears in Yellowstone were probably connected to grizzlies that used to be in the Northern Continental Divide; there certainly were grizzly bears east of here out on the Great Plains. So there was a flow of genes through these populations. Once the grizzly was reduced in numbers -- and it was eliminated from approximately 98% of its historic range in the continental U.S. -- the bear populations that are left, particularly the Yellowstone population, is now isolated from all these other bear populations. It's an island bear population. So we no longer have gene flow coming from other areas. And the concerns revolve around loss of genetic diversity, and the consequences of that loss to long-term population health and stability.
LISSETTE WAITS: Yellowstone Park was once part of a contiguous population of grizzly bears that stretched south to Mexico and east to the Mississippi River. And so what we would like to do, as conservation geneticists and conservation biologists, is restore natural connectivity of the Yellowstone population.
JOHN HOCKENBERRY: Lisette Waits, of the University of Idaho’s Laboratory of Ecological and Conservation Genetics, is responsible for monitoring the genetic diversity of bears. Any bear DNA sampled in the lower 48 states is sent to her.
LISSETTE WAITS: There's a wide variety of ways you can get DNA samples. For the Yellowstone study, we've taken blood samples from bears that are handled by managers. We've taken tissue samples. And we've also collected hair samples on barbed wire and extracted DNA from that.
Barbwire is strung around trees, making some sort of a polygon, and then in the middle you would put a scent lure to lure the bears in. And a real commonly used scent lure is cattle blood and fish guts that have been mixed together and fermented at about 100 degrees for about 6 months. The bears really, really like it, and it's pretty scary for humans to be around that. The bears walk in to check out the scent lure. And they leave hair on the barbed wire; and they walk out again, and often leave another hair sample. It's a really nice system, because the bear doesn't get a reward. The scent lure was just poured on a bunch of logs in the middle. But it does give us a sample of DNA, without having to dart them and handle them and capture them. So that is one of the many techniques that's being used in Glacier National Park, to get an estimate of the population size of grizzly bears and black bears in that ecosystem.
JOHN HOCKENBERRY: To help predict the future for Yellowstone grizzlies, Lissette Waits studies bears from the past.
LISSETTE WAITS: The more diversity a population has, the higher probability that population has for long-term survival and long term persistence. All of the samples that have been held in museums or different collections across the country provide an excellent resource for addressing the question of loss of genetic diversity over time. So we have been working with museum specimens in Yellowstone Park that have been collected since the late 1800s. And we can detect that yes they have lost genetic diversity over time. But they haven't lost as much diversity as we hypothesized. We're also using that data to try to estimate what the effective population size of Yellowstone grizzly bears. You can think of an effective population as the number of individuals that are breeding and passing on genes to the next generation, which is really different from the number of individuals that are actually out there.
MIKE GILPIN: So maybe there are 400 grizzlies in the Yellowstone Ecosystem, but effectively it's more like 60 or 80.
JOHN HOCKENBERRY: Mike Gilpin is Professor of Biology at the University of California- San Diego.
MIKE GILPIN: And no dog breeder, no pig breeder, no chicken breeder would sustain a population of only 60 or 80. Bad genes are going to come up, they're going to increase in frequency, and sooner or later you're going to have fixation of bad traits. Now maybe these traits aren't going to directly cause the extinction of the population. But these things are going to be things like hip dysplasia in dogs, where you maybe don't live as long, immunological issues involving disease resistance.
JOHN HOCKENBERRY: It takes time for the DNA samples in Yellowstone and Glacier National Park to being analyzed. When that DNA becomes data, it’ll end up in the computer of someone like Mike Gilpin.
MIKE GILPIN: Well, I'm a mathematician, basically, and I build computer models. And when this model is constructed you can ask questions of it. You know, what if we design this reserve? What if we move bears from Northern Continental Divide Ecosystem down to Yellowstone? What can we expect? What's the response of the system gonna be? Now it can be corrected in two different ways. You can do man-mediated dispersal; but it would be better to let nature herself take care of this. And so that's the issue of corridors.
JOHN HOCKENBERRY: Corridors are wide swaths of protected land, kind of like biological highways that allow wildlife populations to mix from one habitat to another. Steve Palumbi also studies wildlife corridors in parks… Marine Parks.
STEVE PALUMBI: When I'm talking about a Marine Park, I'm not talking about Sea World, or that little pool you can swim in at Disneyworld -- it's a tiny little enclosed coral reef. What I'm talking about are natural environments that are set aside for people to enjoy and use in perpetuity. They're like our terrestrial parks; like the national parks in Yellowstone, and Grand Teton and state parks, except that they include the marine habitat, as well sometimes as the coastal habitat. And it includes the bays and estuaries and continental slopes, and all the sorts of marine organisms that live in them, not just the organisms that live on land.
JOHN HOCKENBERRY: You heard Steve Palumbi talk before about protecting whales. His current research is on much smaller organisms. He’s trying to figure out how to put the concept of marine parks into practice.
STEVE PALUMBI: We don't really know how to do it, exactly. The reason is a lot of marine organisms, although they may stay within a park as adults, they make eggs and larvae that float away in the water. So what we have to do essentially is design networks of parks, so that the production from one park will essentially be captured by another park
We came to Oregon about two week ago to set up a series of experiments to try to use genetic tools to measure the dispersal distance that marine organisms use to get from place to place. Basically the question is: How far do the larvae and eggs of marine organisms float from their parents before they land somewhere and take up their existence as juveniles or adults for the next generation?
A traditional ecological approach might be to track those larvae. And if the were the size of tunas we could put a little radio transmitter and follow them around the world. Or if they were the size of whales we could put a satellite transponder on and track them that way but these are only a fraction of an inch long, we cannot track them individually
But every time a larva moves from one rocky headland to another, it carries its genes with it. And if we use the technology to understand the movement of genes, then this gives us the information we need about the movement of larva. There's no other way to do it, that we can figure out. That's why DNA has added a whole lot to this work.
JOHN HOCKENBERRY: One of the organisms they look at is barnacles.
STEVE PALUMBI: One of the things we can do with barnacles that we can't do with other kinds of critters is we can put out small plates, small plastic squares, on the rocks, that the barnacles like to land on and settle there to turn into adult barnacles. Week by week we can collect those plates, and look on them and what we can see are little clouds of baby barnacles. They're very tiny; they're about a half of a millimeter, or maybe a fiftieth of an inch long. They don't have a whole lot of DNA in them. But again, modern technology allows us to take this tiny little wisp of a barnacle you can barely see, and get enough DNA out of it to do these genetic tests.
JOHN HOCKENBERRY: For biologists studying DNA, it turns out that many nice things come in small packages. Coming up, we're going to get even smaller, in fact, microscopic; and we hunt for Teenage Mutant Nuclear Gators, when we continue with “DNA, the Code of the Wild” On The DNA Files.

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JOHN HOCKENBERRY: Welcome back to The DNA Files. I'm John Hockenberry. And this is “DNA, the Code of the Wild.”
JOHN HOCKENBERRY: Antony van Leeuwenhoek was an amateur scientist who enjoyed peering through his homemade microscopes, and reporting his observations in letters to the Royal Society of London. On September 17, in the year 1683, he recorded one of the what he saw in the plaque on his own teeth; or, as he said: “a little white matter, which is as thick as if ‘twere batter.” He wrote, “I then saw, with great wonder, that in the said matter there were many very little living animalcules, very prettily a-moving. The biggest sort had a very strong and swift motion, and shot through the water (or spittle) like a pike does through the water.” In the mouth of an old man who had never cleaned his teeth—there’s an image for a scientific revolution—, Leeuwenhoek found “an unbelievably great company of living animalcules, a-swimming more nimbly than any I had ever seen up to this time.” What Leeuwenhoek was describing, of course, for the first time, was living bacteria.
ED DELONG: What we know from some of these studies now is that some of the most ancient organisms on earth are actually the microbes. And in fact, it's the evolution of these microbes, and their physiological properties, biochemical properties that have shaped our planet. In fact the evolution of cyano-bacteria is what gave rise to the evolution of oxygen on earth. And let animals like us evolve.
JO HANDELSMAN: So microbes have been evolving on earth for 4 billion years. And they lived without the higher organisms for most of those 4 billion years. So the microbes would go along just fine if the rest of us disappeared, but if the microbes disappeared, all other forms of life would immediately cease, because the microbes carry out all the major cycles on earth. They control the nitrogen cycle, the carbon cycle, the iron cycle. Just about every major nutrient that enters biological systems enters though the action of microbes.
JOHN HOCKENBERRY: From bears to barnacles to the smaller, microbial world, of bacteria and other microorganisms. Ed DeLong is the Science Department Chair of the Monterey Bay Aquarium Research Institute on the Central California coast.
ED DELONG: Well, right now we're sitting here at Moss Landing. And if you could see down through the ocean, what you'd see is we're right by a canyon that's actually larger than the Grand Canyon.
JOHN HOCKENBERRY: His specialty is looking at what you can’t see. He’s a Marine Microbial Ecologist.
ED DELONG: A real change in our thinking, that's related to this DNA technology, has been our ability to relate all these micro-organisms with macro-organisms, plants and animals, on one evolutionary tree. We never could do that before. Because in biology, the way that we relate things is based on similarity really, homology. We know that dogs and cats, for instance, are mammals because they share certain features. And we can distinguish them by their differences. We can't do that with microbes, and we can't compare microbes to higher organisms, because they really don't share any similar morphological or other conspicuous properties. So how do we compare them?
And it turns out that we can compare them when we look at things like DNA and compare sequences that all organisms share in common. We can start to see how similar they are, how different they are, and how they're related.
JOHN HOCKENBERRY: Jo Handelsman, of the University of Wisconsin Molecular Microbial Ecology Group, regularly goes out and digs up soil samples, then brings them all back to the lab to find out, as she says, “who’s there.”
JO HANDELSMAN: We can find the DNA of organisms even when we can't see the organisms. So in my field we study microorganisms that live in soil and in the oceans and all throughout the biosphere. And DNA has really allowed us to see what we think of now as the unseeable, and the previously unknowable organisms.
JOHN HOCKENBERRY: Unknowable, not because they’re too small, but because up until recently, for the most part, scientists only knew the microorganisms they could grow in the lab, in their petri dishes or petri plates.
JO HANDELSMAN: All of the history of microbiology until the last few years has been based on culturing organisms, growing them on Petri plates. But, over the last 30 years we noticed, that, in fact, most of the organisms in the world don't grow on Petri plates. And in the soil, where I work, 99% or maybe as much 99.9% of the microbes don't grow on Petri plates. But we know they're alive and living and doing interesting things in the soil.
So the challenge has been to try to understand who those microbes are, and find ways to study what they do. And DNA has allowed us to do that, because we can find their DNA signatures in the soil, even if we can't grow those organisms in culture.
JOHN HOCKENBERRY: We’ve described only a tenth of a percent of the microbial world so far, but it's an important world. In fact microbes are family, folks. Humans are genetically related to brewer’s yeast from a billion and a half years ago. Of course, we’ve grown distant then, we don’t call, we don’t write. But even after a billion years of evolutionary distance, there are still DNA sequences in yeast and humans that are identical. Some genes you could take out of yeast, put them inside a human cell, and they would function. So what if, in one of these ancient microbes, we found a gene that resists aging? James Tiedje is Director of the Center for Microbial Ecology at Michigan State University. He’s just begun studying some of the oldest and coldest organisms on the planet.
JAMES TIEDJE: One of the interesting projects that were working on is to understand the microbial adaptation that has occurred in ancient Siberian permafrost environments. So our Russian colleagues have studied microbes that have been frozen in the soil for up to 3 million years. And we can recover living organisms from those environments.
[hissing sound]
JOHN HOCKENBERRY: That’s the sound of Cosmic Background Radiation, Cosmic Rays, coming from outer space. They’ll make a Geiger Counter click as much as once a second.
We’re constantly bombarded by a low-level background radiation, not only from space, but also from soils and rocks. Naturally occurring radioactive elements, like Uranium, decay and emit radiation. Over time this background radiation can cause mutations, errors in the DNA sequences.
JAMES TIEDJE: Because of the background radiation in the soil, these organisms would have had their DNA destroyed over that period of time, had they not had DNA repair mechanisms operative.
JOHN HOCKENBERRY: Cells constantly find and fix mutations in their DNA. James Tiedje wonders if cells packed in permafrost for a few millennia repair their DNA in the same way as their room-temperature relatives.
JAMES TIEDJE: It's argued, from a theoretical point of view, these microbes in this permafrost environment are metabolically active, at a low level, over this period of time. So they're not simply arrested in life, but they are carrying on a slow metabolism to repair their DNA and their membranes, for example, over that 3 million years.
And we're interested how they have adapted to the stresses in this environment. And we consider the stresses to be, of course, how does life go on at minus 12 C, over hundreds of thousands of years? How do these microbes adapt to the starvation that goes on in this environment? And finally, how do they adapt to cell aging -- because the body parts of these microbes are probably pretty old? A microbe may have his same membrane for 10,000 years. What's in their genetic code that has allowed them to survive under these conditions for that long?
[sounds of paddling boat on water and all kinds of night pond critters]
TRAVIS GLENN: We've got a John-boat, a small 14-foot John-boat. And what we're going to do is start looking for alligators on Pond B.
JOHN HOCKENBERRY: At the somewhat forbidding federal Savannah River nuclear Site, in South Carolina, Travis Glenn is studying the effects of radiation from a quite different source.
TRAVIS GLENN: What’s unique about Pond B is there was a release of radioactivity from the R Reactor on Savannah River Site, in the early 1960s, so there's elevated levels of Cesium 137 and Strontium 90.
JOHN HOCKENBERRY: The goal here at Savannah River was to manufacture weapons-grade plutonium and tritium for Cold War H-bombs.
TRAVIS GLENN: Really the emphasis was on building bombs faster than the Russians could. If they happened to have a few spills and accidents, well that's part of the price you pay for war, even though it was a cold war.
JOHN HOCKENBERRY: 21,000 people once worked here making bomb materials. Now 14,000 people are employed cleaning up the mess. Travis Glenn is head of the DNA Lab at the Savannah River Ecology Center, which monitors the wildlands and wildlife on the site. Sometimes that means going out at night, in a boat, and using headlamps and flashlights to search for the reflecting eyes of living creatures in the potentially irradiated water.
TRAVIS GLENN: What were trying to do is look at genetic variation in alligators, the effects of site operations on the alligators, and then also we're characterizing the mutation rate between the parents and offspring.
The Savannah River Site is second only to Hanford in the total volume of water and soil that have been contaminated, but also if you look carefully at what the levels are, the levels are really low. Yes, you can detect a level of contamination that's above background. But is it biologically meaningful, that's the real question. Because certainly you can see that's it's an intact ecosystem. There's lots of trees and wildlife here.
And so if you spent the hundreds of millions of dollars that it would take for you to drain the lake, dredge out all the sediments, and haul it off to a landfill and bury it, have you really gained anything? For sure, you've ruined it ecologically for some time to come relative to what it's like now.
There's a gator right straight in front of us. See the orange glow? Looks like sort of a burning ember of charcoal? So if this is the same gator that was back here last spring, it's about a six-foot alligator. So I think when we hauled him out last June, he was a little over 5 feet, so he should be pretty close to pushing 6 feet if it's the same one. And I don't need to catch them more than once. Now you can see how close we can get. We're almost close enough to put a noose on him.
JOHN HOCKENBERRY: The question Travis Glenn poses is how much environmental damage are we willing we risk to clean up environmental damage?
TRAVIS GLENN: If you look out here this is one of the worst-case scenarios in an ecological setting of lots of wide spread contamination. And there's no indication of a change in mutation rate, which is certainly what you'd expect. So the question is: Is there real any biological effects of the low-level contaminants that we see? And I think they'll be a lot of places like where we’re sitting where this new field of phytoremediation, and monitored natural attenuation, which is sort of leave it in place, let the natural processes take care of the residual effects of the contaminants; because really anything that you could go in there and do with bulldozers would be far more harmful than just leaving it alone.
JOHN HOCKENBERRY: Which wouldn’t be the first time in human history caused more problems than they were trying to solve. But did you catch that word Phytoremediation that Travis Glenn said a minute ago?
LAURA CARREIRA: Phytoremediation is the use of living plants to clean up contaminated sites.
JOHN HOCKENBERRY: Biochemist Laura Carreira is a pioneer in phytoremediation. She co-founded Applied PhytoGentetics, the company hired to clean the Georgia State Botanical Gardens.
LAURA CARREIRA: To our left is what used to be an old solvent dump from the University. This is University property. They used to bring solvents from all the research labs out here and dump them in a lethal solvent dump. You can see all the fences around, and the tress have grown up around it. To my right is an unnamed wetlands where all the solvents are now starting to come out.
JOHN HOCKENBERRY: The way to clean most contaminated sites, and the way the University was planning on cleaning this one, is to dig up all the dirt and haul it away.
LAURA CARREIRA: It would have taken more than a year, it would have shut down the Botanical Gardens, it would have cost about 20 million dollars. That's the standard procedure: cart if off to a hazardous waste landfill; let somebody else take care of it. (laughs)
JOHN HOCKENBERRY: Carreira estimates that using phytoremediation on this site, including long-term monitoring, will cost only about a half-million dollars, and will remove all the toxins. Her strategy is to find native plants, growing on the site, that use toxins as nutrients; they turn the toxic chemicals into harmless byproducts, carbon dioxide and water.
LAURA CARREIRA: When we first started this we were looking for any plants which could tolerate growing in polluted sites. So what we did was that we came out here and analyzed 68 different plants, looking for the enzymes that would degrade the solvents that are in the water. And then last December we planted 5600 plants of 9 different species. And now we're going to monitor all next year to make sure absolutely nothing is getting off the site. The highest concentrations of the solvents are coming right down this hill. That well right there has 50 parts per million total VOC's, which is methylene chloride, chloroform and benzene. I put 150 hickory trees going up that hill. And then we started over here and put Yellow Poplar, Sweet Shrubs, Beauty Berry, Sweet Bay, Cypress trees. We left every Azalea on the place; nobody could dare cut any Azaleas (laughs). It doesn't have to be ugly to clean it up. That's the beauty of organic phytoremediation, is that it turns it into non-toxic compounds which are just part of the tree, part of the shrub. You don't have to do anything (laughs). But we can use the fact that they have the ability to do this, to clean up something that we caused, while also making something pretty. I tell everybody that you need to walk softly, and let the plant's take care of us all. Because they will.
JOHN HOCKENBERRY: Another co-founder of Applied PhytoGenetics is Richard Meagher. He’s working on a tougher problem in pollution control: toxic heavy metals that come from industrial waste, things like arsenic, cadmium and mercury. No plants have been found that can efficiently remove these metals from the soil. So he’s building some that will.
RICHARD MEAGHER: So what's going on here is we're trying to prove that adding one new gene is going to make these plants resistant to arsenic. And what you'll see is that the control plants are only a few millimeters long, and are looking very sick and yellow, and they're all going to die. And the ones with this one new gene, they're growing real well. They're already going on to flower. They're looking really healthy and have nice long roots a couple inches long. This tells us that this gene will help the plant be tolerant or resistant to arsenic. That's sort of our first step in terms of making a plant that would clean up an arsenic contaminated site. Arsenic is one of the worse five metals on the EPA's hit list for things to be cleaned up so this is just of the beginning of our arsenic project. We think it's gonna take us about five genes total to engineer a plant that would very efficiently phytoremediate arsenic, extract it and allow us to efficiently take it from the plant.
JOHN HOCKENBERRY: The plants actually take the metals into their tissues. But once the metals are in the plants, it still must be harvested and disposed of. Yet these transgenic plants may solve the previously unsolvable problem of getting the metals out of the soil. Transgenic plants used in phytoremediation are still in the greenhouse, or in confined research plots. But transgenic bioremediation products may soon be leaving the laboratory. Bioremediation is the use of microbes, instead of plants, to clean contamination. Gary Sayler directs the Center for Environmental Biotechnology at the University of Tennessee. He has received the first EPA approval to field test transgenic microorganisms for cleaning up hazardous waste.
GARY SAYLER: And we do that by genetically engineering microbes to degrade specific pollutants, but also introduce into those organisms the genes that allow them to make bioluminescent light. The organism as it begins to degrade that toxic chemical turns on these genes for light production, and the organisms give off light. To do away with toxic chemicals, the idea would be to keep the light on as long as possible.
Now that work is actually moving into new directions where we're integrating these organisms directly on silicon microchips to make tiny remote sensor technology that would allow individuals to use these organisms as very low cost, but very specific sensors of chemical contaminants in the environment. It could have broad implications for soil and water monitoring, even toxicants associated with food. The home residential user could be using it for testing their own well water.
JOHN HOCKENBERRY: Amazing critters, these microbes. And the most amazing, the Superbug, Deinococcus radiodurans, among the world's toughest and oldest organisms, you haven’t heard of it? Well, if you ever see it, It's pink; smells like rotten cabbage. It can survive an atomic blast, acid baths, high and low temperatures, ultraviolet radiation, and dehydration. How’s that for conditioning? By the way, it can take 1.5 million rads of gamma radiation, that's 3,000 times the lethal dose for humans. It lives in cow pies and elephant dung. It's 2 billion years old, and came to the attention of scientists when it refused to die in post-World War Two sterilization tests on canned meat. Researchers call it Conan the Bacterium. Bio-engineers have plans to engineer its genome for a variety of purposes, from eating nuclear waste to providing medicine for Mars-bound astronauts.
So what happens when transgenic creatures, like the perhaps soon-to-be-modified Superbug, mingle with the rest of the not-so-super species? What happens when animals munch on metal-absorbing genetically modified plants? Well, we don’t know yet. Most of the bio-engineered phtyo- and bio- remediating organisms are still in the lab.
JANE RISSLER: About 17 years ago, when people were first starting to talk about commercializing genetically engineered organisms, microbes for bioremediation was a pretty big topic. To use in oil extraction, to use in mineral extraction. There were a lot of suggestions about microbes, but interestingly, they haven't worked very well. Because they certainly have not moved towards commercialization.
JOHN HOCKENBERRY: Jane Rissler is Senior Staff Scientist at the Union of Concerned Scientists.
JANE RISSLER: Ecologically there are more challenges than there are genetically. And we know so little about, for example, the soil or water microbial world, that we just don't know what we're doing when we release transgenic microorganisms into these environments.
JOHN HOCKENBERRY: One of the fathers of ecology, Aldo Leopold, said: “To keep every cog and wheel is the first precaution of intelligent tinkering.”
JANE RISSLER: What we have learned, or should have learned in the last 20 years, is that we need a lot more ecology to understand how to use genetically engineered products.
STEVE PALUMBI: It definitely is a discovery period. We’re just now taking baby steps; kind of evolving ways to understand, really, our planet in a more holistic kind of systems based approach.
JO HANDELSMAN: We've seen a merger of the techniques of molecular biology with those of ecology.
JOHN AVISE: I fully anticipate that within the next 20 years that entire tree of life will be illuminated almost completely. And I think this will a milestone event in the history of biology that will rank with the human genome sequencing project as a tremendous milestone, a great accomplishment in the history of biology.
STEVE PALUMBI: Because DNA is fundamentally built the same, whether it's in humans or whales or barnacles, we can use the technology developed, say, for doing genetic tests in your doctor's office, to ask questions about the ecological situation these animals are in that we couldn't answer in the past. And, really, if you think about it, that was the promise of the human genome project, that we'd have this technology to use in wide-ranging applications all over the world.
JOHN HOCKENBERRY: Even some of the most serious biologists get a little starry-eyed when they talk about Aldo Leopold's 1948 memoir, A Sand County Almanac. Let me read a bit: “It is a century now he said, since Darwin gave us the first glimpse of the origin of the species. We know now what was unknown to all the preceding caravan of generations: that men are only fellow-voyagers with other creatures in the odyssey of evolution. This new knowledge should have given us, by this time, a sense of kinship with fellow-creatures; a wish to live and let live; a sense of wonder over the magnitude and duration of the biotic enterprise.”
We've certainly come a long way since 1948 and Aldo Leopold would be amazed by the technological advances since then. But I think if he were here now, he would also agree, that we're still waiting for that wisdom.
I’m John Hockenberry. Thank you for listening to The DNA Files.

CREDITS:
This series, The DNA Files, was produced by SoundVision Productions with funding by the National Science Foundation and the Alfred P. Sloan Foundation.
This program, DNA, The Code of the Wild: Genetics and Applied Ecology, was produced and engineered by Barrett Golding. The editor was Sora Newman, and our host was John Hockenberry.
Our opening feature, “Low-Mow Lawns,” was produced by Erik Anderson, and edited by Gemma Hooley.
The DNA Files is: Managing Editor, Rachel Ann Goodman. Science Consultant, Sally Lehrman. Research and Production support by Adi Gevins and Noah Miller. Technical and Music Director, Robin Wise.
Original music composed by Jesse Boggs and performed by the Stanford Woodwind Quintet, Anton Schwartz, Tom Hayashi, and Jesse Boggs.
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You can visit our website at www.dnafiles.org. Send your responses and letters to feedback@dnafiles.org. For tapes and transcripts, call 866-DNA-FILES (866-362-3453).
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

Life: How to Make a Cosmic Omelet
Genetics & Astrobiology

Hosted by John Hockenberry

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Last reviewed for accuracy: February 2002.
JOHN HOCKENBERRY: Welcome to The DNA Files. I’m John Hockenberry. In this program, Life: How to Make a Cosmic Omelet, we’ll be looking at where life came from, and what genetic research is telling us about where else we might find it. The National Aeronautics and Space Administration—NASA—has dubbed the field Astrobiology, a marriage of sorts between astrophysics and biology. As we’ll see, it’s not the search for little green men, but rather the search for any sign of life at all. Even microscopic life. It may be one of the most difficult and most rewarding challenges facing science today, says physicist Paul Davies.
PAUL DAVIES: There can surely be no greater challenge than to understand how a mixture of non-living chemicals turn themselves spontaneously into the first living thing.
JOHN HOCKENBERRY: All this when we return with The DNA Files.
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JOHN HOCKENBERRY: Yellowstone National Park. For most of us, it’s a spectacle of geysers and bison; for genetic scientists it’s a hotbed of microbial research, home to nature’s tiniest creatures. What scientists are learning here may help us unravel the biggest puzzles of all time: How did life get started? And what are the most extreme conditions in which it can survive? Joe Jordan has this story…
JOE JORDAN: Imagine the early earth, more than three and a half billion years ago. Boiling mud pools, toxic chemicals … big chunks of rock and ice crashing in from the sky. How could anything have lived through these conditions? For answers, scientists come to a place where our planet’s internal heat still leaks out, in scalding steam geysers and brilliantly colored hot springs teeming with life …
TIM MCDERMOTT: Welcome to Yellowstone National Park, Joe. G'morning; it's a great day to be here in Yellowstone, and it's a great place to work.
JOE JORDAN: That’s Tim McDermott, a soil microbiologist at Montana State University’s Thermal Biology Institute. He studies microbes that live here in the 200-degree Fahrenheit geothermal pools of Norris Basin, a volcanically active backcountry area of the park. Some of these microbes even live on arsenic – a poison to us, but one of several heavy metals found naturally here in Yellowstone.
TIM MCDERMOTT: Mercury, lead -- copper, zinc if it weren't a national park, at least places would probably be designated a super-fund site.
JOE JORDAN: At the edge of a bubbling hot spring, McDermott samples soil for microbes. Back in his lab, he’ll study variations among their genes for arsenic tolerance. Plotting where microbes live and what they eat helps color in the map of evolutionary relationships, from ancient to modern organisms. But most of what we know about microbes comes from being able to analyze their DNA, says University of Colorado molecular scientist Norm Pace.
NORM PACE: Imagine if our entire understanding of biology were based on a visit to the zoo ... And that's exactly the situation we've been at in the microbial world until really quite recently.
JOE JORDAN: In fact, an organism discovered here in Yellowstone gave scientists the enzyme used in most new gene sequencing techniques. Out in Norris Basin, Pace’s colleague, biologist John Spear studies the hydrogen diets of microbes in the crystaline turquoise blue, green and yellow waters. He takes DNA snapshots of whole microbial communities in their natural habitats.
JOHN SPEAR: What I'm doing is I hang a piece of glass -- just regular glass, like a window-pane glass -- I hang it in the pool and I'll come back and get it in 2 weeks or 3 months -- I'll give it an amount of time for it to get colonized with a bio-film.
JOE JORDAN: Spear uses a razor blade to scrape the microbial film off the glass into a tube that he freezes in liquid nitrogen. Then he takes it back to the lab, extracts the DNA and plots similarities and differences between groups of microbes. What starts to emerge is a map of the tree of life, of evolutionary relatedness. Spear’s wearing a tree-shirt today.
JOHN SPEAR: On this t-shirt we have a picture of a tree. It's a tree that has the 3 major groups, or domains, of life – the Bacteria, the Archaea and the Eukarya.
JOE JORDAN: Eukarya is where we humans are on the tree of life, along with all the animals, plants and fungi. Most of us know something about bacteria, too. But Archaea, A-R-C-H-A-E-A -- the name implies ancient heritage. Once thought to be among the bacteria, they've recently been revealed as a whole new category -- with significant differences between their DNA and that of all other modern life. They may be closely linked to the earliest life forms, near the root of the tree, explains Norm Pace.
NORM PACE: When you look at these high-temperature organisms -- particularly the high-temperature Archaea -- you see these very short line segments departing from the last common ancestor.
JOE JORDAN: Archaea turn up everywhere from oceans to the human gut. Among them are many "extremophiles,” organisms that can live in exotic conditions like heat, acid, salt and ice … places we never thought we’d look for life. Astrobiologist Jonathan Trent of NASA’s Ames Research Center in California studies how some of the heat-loving microbes beat the heat by making a heat-shock protein that appears to stabilize cell membranes. He reflects on how genetic adaptations like these are expanding the realm of the possible, opening whole new worlds, in our view of life.
JONATHAN TRENT: It’s probably comparable to the age of discovery that went on in the 19th century, where people were going around on ships and they were finding things living in the deep ocean, in places we had no way of ever visiting before … and now were going in that same direction with the inventories of DNA information that more and more organisms are being sequenced. And many people are now saying that the 21st century is going to be the age of biology.
JOE JORDAN: Now that we are beginning to map the range of extremes in which life can survive, what we learn in Yellowstone could help us plan where to look on upcoming missions to Mars and Europa, environments that now seem just a bit more likely to harbor at least some form of life…
For The DNA Files, I’m Joe Jordan.

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JOHN HOCKENBERRY: Welcome to The DNA Files. I'm John Hockenberry. In this program we’ll meet scientists studying the origins of life on Earth and searching for the signs of life beyond Earth. For my own part, I want to know where I’m from. I mean I know where I was born, and where my parents were born and all that. But where am I really from? Where did any of us come from? We’ve asked this question as long as there have been humans to ask it.
VOICE: In the beginning, there were two realms. Muspell was in the south, and it was full of fire and blinding light. Niflheim, the home of fog, ice and snow, lay in the north. Between the two realms was a vast stretch of empty space called Gin-nun-ga-gap, or Yawning Gap.
JOHN HOCKENBERRY: There are probably thousands of stories that start with "in the beginning" and so on, to recount how life began. Every culture has at least one such tale. This one is from Iceland.
VOICE: The drips and drops started life growing…
JOHN HOCKENBERRY: To many ears, such tales sound far-fetched, if taken literally. But scholars of religion and folk traditions like Professor David Leeming say creation tales undoubtedly satisfy a universal human need for an answer to why we’re here. Dr. Leeming, is an emeritus professor of English and comparative literature at the University of Connecticut and author of the "Encyclopedia of Creation Tales."
DAVID LEEMING: Why did people in the Paleolithic dig their way down into caves and sit there in the darkness and then paint paintings, of animals and shamans or whatever? It’s as if we’re driven to tell the story of creation.
JOHN HOCKENBERRY: And it's not just storytellers and shamans who are driven to explain the origins of life, says Leeming.
DAVID LEEMING: And it’s also told by the scientist who says, "Hey, we are all the result of an explosion that took place in a billionth of a second billions of years ago.” There’s a relationship between what the old mythmakers were doing and what the scientists are doing.
JOHN HOCKENBERRY: Some scientists have theories that make the Icelandic story of Yawning Gap seem positively mainstream.
CARL SAGAN: With 400 billion stars in the Milky Way galaxy alone, could ours be the only one with an inhabited planet?
JOHN HOCKENBERRY: Take the late professor Carl Sagan, who used his public television program Cosmos to spread his conviction that advanced life must be common in the universe.
CARL SAGAN: Perhaps near one of those pinpoints of light in our night sky someone quite different from us is glancing idly at the star we call the sun and entertaining just for a moment an outrageous speculation.
JOHN HOCKENBERRY: Sagan was one of the country’s leading proponents of the search for extraterrestrial intelligence. He inspired a generation of scientists and science buffs dedicated to the quest for alien beacons. And he authored Contact the story of a scientist obsessed with finding extraterrestrial life. The book later became a major motion picture.
But many scientists say fishing for intelligent extra-terrestrials at the top of the galactic food chain is unlikely to be successful, even if there are aliens somewhere out there with transmitters trying to reach us. They say the scientific payoff is closer to home, on planets in our own solar system, looking for the simplest life forms possible—single-celled organisms like bacteria and yeast. Biologist Lynn Rothschild.
LYNN ROTHSCHILD: Where the interest is going to be is at the molecular and really the microscopic level. If we find anything that’s alive, no matter how microscopic, no matter how simple in a metabolic sense, that is the most exciting thing. It’s this whole question of life or non-life.
JOHN HOCKENBERRY: A scientist at NASA’s Ames Research laboratory in California, Rothschild says apart from such single-celled microbes, life is probably rare in the universe. The evidence comes from looking not up but down, at the Earth under our feet. On this blue ball we call home, single-celled life made its dramatic entrance some 3.8 billion years ago, but it wasn’t until about half a billion year ago multi-celled plants and worms and the like joined the cast.
CHARLES LIU: We’re here in the northwest corner of the Rose Center and we can see clearly the hanging and mounted models of the planets as we’ve displayed them...
JOHN HOCKENBERRY: To better understand the plot of this cosmic melodrama, we’ve made a visit to New York, to the Rose Center of the American Museum of Natural History.
CHARLES LIU: Earth in front of us here is about the size of a basket ball, Mars—with its red surface and white ice caps…
JOHN HOCKENBERRY: Physicist and museum curator Charles Liu is my guide. Models of electrons, protons, planets and stars illustrate the size of the universe and everything in it. A broad ramp called the Cosmic Pathway illustrates its age.
CHARLES LIU: And it is a 349-foot long spiral walkway--so it’s about as long as a football field plus one and a half end zones. Along this pathway, which describes the entire history of the universe, 13 billion years of cosmic evolution from the big bang to the present day.<