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

Designing The Garden:
Food in The Age of Biotechnology

Hosted by John Hockenberry

Transcript

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and the Alfred P. Sloan Foundation.
JOHN HOCKENBERRY: It can be tough to decide what to buy at the supermarket these days. We hear a lot about genetically modified foods, but do you know which foods are modified or not? And what does genetically modified mean, anyway? This is The DNA Files. I'm John Hockenberry. Today's program is called, "Designing the Garden: Food in the Age of Biotechnology." Over the next hour, we'll visit coffee connoisseurs in California, soybean farmers in Ohio, and nutritionists in Southern India.

LAKSHMAN: So we are looking at the ultimate objective of "Are we able to reduce child mortality down to numbers, which are far lower than the kind of unimaginable numbers that we have today?"

JOHN HOCKENBERRY: We'll hear about scientists putting genes from daffodils into rice, DNA from mice into pigs, and a gene from bacteria into corn, all to better understand food created for the dinner table, coming up after the news.
...
JOHN HOCKENBERRY: Welcome to The DNA Files. I'm John Hockenberry. And if there was like a theme park to food, it would be right here at the Fairway Market in Brooklyn, New York. I'm surrounded by produce--plums like an ocean of--oh, man, those are--yeah, I need this--and everybody's summer favorite, corn. Look at that. Look at that. Oh, man. Dinner.
JOHN HOCKENBERRY: Is this real yellow?

WOMAN 1: Is that real yellow?

JOHN HOCKENBERRY: Do they grow like this?

WOMAN 1: Yeah. Are you worried that it's like been genetically altered or something?

JOHN HOCKENBERRY: No. Do you worry about that?

WOMAN 1: I don't know. I don't really think about it so much, but that's--that's good.

JOHN HOCKENBERRY: That’s the real deal.

WOMAN 1: That's the real deal. [laughs]

JOHN HOCKENBERRY: Yeah, all right, thank you.

WOMAN 1: You're welcome.

JOHN HOCKENBERRY: Genetically modified foods, also called GM foods. That's when scientists modify a plant or an animal's genes in the lab. Sometimes they'll add new genes. Sometimes they'll turn off a gene so it stops working. Hardly any genetically altered plants wind up here in the produce aisle, maybe some yellow crookneck squash, an occasional papaya, but more than 70% of the corn grown in the U.S., and 90% of soybeans are genetically modified. And a lot of corn and soy shows up in processed foods.

Come with me. I'm going to head over to the cereal aisle here. We got Special K Protein Plus here, wheat bran soy grits, rice, wheat gluten, soybean oil, whole grain wheat, soy protein isolate, sugar, salt, high fructose corn syrup, malt flavor, natural ...

A lot of GM corn and soy is processed into these kinds of things--soy protein isolate, high fructose corn syrup, and it ends up in cereals, juice drinks, frozen pizzas, you name it.

LEE SILVER: So what? [laughs] I guess is the question.

JOHN HOCKENBERRY: Lee Silver is a professor of molecular biology and public policy at Princeton University. He's on one side of the GM food debate. He says pretty much everything we eat, processed or not, has been manipulated by humans. For example, he says corn as we know it today is essentially a human invention.

LEE SILVER: If you go out into the Midwest and you go outside of a farm, corn doesn't grow in the woods. It didn't exist before people in Central America took a weed, and began to select characteristics, which are actually bad for the corn, but good for people.

JOHN HOCKENBERRY: Ten thousand years ago, an ear of corn had no more than 12 little kernels. This ear of Silver Queen at the market today--umm, it's got to be 500 kernels. In Lee Silver's view, genetic engineering is just an extension of the plant breeding that's been going on for thousands of years. But another scientist says, "Unh unh, no. Selective breeding and genetic modification are very different. Mardi Mellon is with the Union of Concerned Scientists.

MARDI MELLON: I would argue that that's a radical departure from the technology of traditional or conventional breeding that's based on the selection of organisms and the controlled mating between organisms.

JOHN HOCKENBERRY: Mellon says traditional breeders work with plants that are closely related to those they're manipulating.

MARDI MELLON: Over time, we have accumulated an immense amount of experience with selective breeding, and one of the things we've learned is that if you stick with the set of genes that can be accessed through traditional breeding, i.e., the wheat that you want to modify can only be done by breeding the wheat plant with wheat or a near relative, that we have an idea of what kind of outcomes those limited genetic combinations produce.

JOHN HOCKENBERRY: Genetic engineers put daffodil genes into rice and bacteria genes into corn. Mellon says adding genes from unrelated species could create new risks to the environment and perhaps to people.

LEE SILVER: I think that's misleading.

JOHN HOCKENBERRY: Here's Lee Silver again.

LEE SILVER: The culture is such that people think GM food is dangerous. Now, the products that are on the market right now in the United States, there's no evidence that they've caused any detectable harm.

JOHN HOCKENBERRY: It's been more than a decade since GM products began making their way on to our dinner tables. In 1994, the Food and Drug Administration approved the “Flavor Saver” tomato. Consumers didn't like it. So you won't find it at the supermarket any more. But in 1996, the Monsanto Corporation came out with something that started a revolution in American farming. Today, more than 100 million acres of American farmland are planted with GM soy, corn, cotton, and a few other crops.

MAN 1: Today, agriculture is going far beyond Nature to produce new miracles for an even better, more abundant life.

JOHN HOCKENBERRY: Monsanto's innovation was the Roundup Ready soybean seed. Roundup is a well-known weed killer for homeowners and farmers alike. Monsanto came out with it more than 30 years ago, but now the company is selling is with a biotech seed that works together with the weed killer. Eric Sachs is chief of Monsanto's global scientific affairs group. He says that when someone sprays the Roundup weed killer, it binds with an essential enzyme in plants.

ERIC SACHS: That enzyme is critical for the production of certain amino acids.

JOHN HOCKENBERRY: And Roundup makes the enzyme inactive.

ERIC SACHS: So when it's inactivated in the weed, the weed eventually dies, because it's starved for those critical amino acids.

JOHN HOCKENBERRY: To create Roundup Ready seeds, scientists took a gene from a bacteria and added it to a plant's DNA. The new gene alters the shape of that critical enzyme.

ERIC SACHS: Think of something like a little kidney bean, where it has a small, little space in it where the Roundup molecule might fit. In the Roundup Ready gene, that space is altered slightly so that the molecule doesn't fit any more.

JOHN HOCKENBERRY: So in Roundup Ready plants, the weed killer can't bind, and it can't kill the plant. Farmers can spray all over a field of Roundup Ready corn or soy, and kill the weeds, not the crops. This Roundup Ready technology has been a huge boon for Monsanto. Sales of GM corn and soybean seeds totaled more than two billion dollars in the first half of 2007. That's in addition to almost 1.2 billion dollars in sales for the weed killer alone. But some U.S. farmers want to keep genetically modified plants out of their fields. These farmers worry that GM plants growing nearby could contaminate their fields and ruin their markets, and they think it's the government's responsibility to protect them. One of the biggest victories for anti-GM forces came in May, 2007. For the first time, farmers were forced to stop planting a biotech crop, because of a federal court ruling. DNA File's producer, Julie Grant, brings us the story of Roundup Ready alfalfa.

JULIE GRANT: Except for a few sprouts, most of us don't eat alfalfa, but cows do, and we drink milk and eat meat from those cows. If you want your milk and meat to be organic, your cows can't be eating genetically modified plants. The national organic rules are strict about that. In 2005, Monsanto put Roundup Ready alfalfa seeds on the market, and in just two years, nearly half of all alfalfa farmers switched to it.

A river flows around this farm in Northern California. Glenn Nakagawa has the trim build of a man who's worked a lifetime in these fields, but now Nakagawa's getting older. He wants a crop that won't take a lot of tending. He decided to plant Monsanto's new genetically modified alfalfa, because the Roundup Ready seeds are supposed to make it easier to keep weeds, such as lamb's quarters or wild mustard at bay.

GLENN NAKAGAWA: What's left is nice, green, thick stand of alfalfa.

JULIE GRANT: He's glad he chose Roundup Ready alfalfa.

GLENN NAKAGAWA: The nice thing is, you're paid on cleanliness of your hay. The more alfalfa you have in the bale, the more money you're going to get paid for that hay. If you have a lot of weeds [laughs], you're going to get paid for the weeds, and it won't be as much money.

JULIE GRANT: Nakagawa paid two to three times more for the biotech seeds, but he expects to use less herbicide. That will save him 30 to 50 dollars per acre. It also means less chemical run-off into the river. But ever since Roundup Ready alfalfa went on the market, it's pitted farmer against farmer. Glenn Nakagawa got his Roundup Ready alfalfa planted before the ban. Farmer Albert Straus wishes sales had been halted sooner. Nearly 15 years ago, Straus decided to have his family's farm certified organic.

ALBERT STRAUS: We do glass bottle organic milk, organic butter, yogurt. We make ice cream as well.

JULIE GRANT: In order to get the little round seal--the organic certification on his milk bottles and other products, everything he feeds his 270 cows also needs to be certified organic.

ALBERT STRAUS: We buy about 50% of our feeds every year. We probably buy about 3,500 tons of alfalfa a year, and that comes from either Northern California or Nevada.

JULIE GRANT: But when Straus tested the so-called organic corn in the feed he bought, more than a quarter of it was genetically modified.

ALBERT STRAUS: I was shocked. We verified with this higher standard test. I sent the sample to the lab, and they found that it was contaminated with three traits of genetically modified organisms.

JULIE GRANT: Straus was worried when he heard more farmers were starting to plant Roundup Ready alfalfa.

ALBERT STRAUS: They're not able to control the GM corn. They're not going to be able to control the GM alfalfa.

JULIE GRANT: But corn and alfalfa don't carry the same risk of cross-pollination. Each corn plant can produce millions of pollen. On a breezy day, corn can cross-pollinate plants hundreds of feet away. Alfalfa often pollinates itself, and when it does cross-pollinate, it's by bees. Honeybees don't spread pollen as far as the wind.

Dan Putnam is an alfalfa expert at the University of California at Davis. He wrote a brief to the court that was used by the U.S. Department of Agriculture and Monsanto to argue that alfalfa has low risk of gene flow. He and his colleagues tested non-genetically modified alfalfa growing 165 feet from GM alfalfa. The contamination levels were one-quarter of 1%. Putnam said bees just aren't very interested in alfalfa.

DAN PUTNAM: They do not like alfalfa, because it trips and hits them in the head.

JULIE GRANT: Putnam explains that when a bee lands on the flower, one of the petals tenses, jerks forward, and strikes the bees. He says there's another reason that cross-pollination or gene flow is unlikely from a field of alfalfa grown for hay.

DAN PUTNAM: Most growers manage gene flow just because of what they do with hay fields. They cut them frequently, and they don't allow them to flower very much, and they certainly don't allow them to set seed.

JULIE GRANT: Hay farmers want the plants' energy to go into making thick, green leaves, not into flowers. Putnam says that, coupled with the bees' dislike of alfalfa, make the potential for contamination in hay fields close to nil. But even the tiniest amount is too much for many organic farmers. The federal court that banned the GM alfalfa wanted more evidence. The judge instructed the USDA to prepare an environmental impact statement, something it hadn't done on any Roundup Ready crops. The study is expected to take up to two years. In the meantime, Monsanto has had to recall all the seeds from its distribution chain. For The DNA Files, I'm Julie Grant.

JOHN HOCKENBERRY: Coming up, how to reduce pollution with a genetically altered pig and how one scientist stops the coffee plant from making caffeine when we continue with "Designing the Garden: Food in the Age of Biotechnology" on The DNA Files.

...
JOHN HOCKENBERRY: Welcome back to The DNA Files. I'm John Hockenberry. We just heard how the courts are forcing government agencies to do better research on the environmental effects of one GM crop. There's a lot at stake for biotech companies, for farmers, and consumers. So now, let's go back to the studio with Mardi Mellon and Lee Silver, our two experts who in some ways are acres apart on the subject of GM foods. All right, Mardi Mellon, who regulates genetically modified foods and crops?

MARDI MELLON: Three agencies do--the Food and Drug Administration, the United States Department of Agriculture, and the Environmental Protection Agency all have some piece of the biotech regulatory pie.

JOHN HOCKENBERRY: And they're all in total agreement about everything, Lee?

LEE SILVER: No. They're supposed to regulate different aspects of the process. Obviously the Environmental Protection Agency is looking at impact of growing crops on the environment, and you have the USDA, which is looking at agricultural levels. The Food and Drug Administration is looking at the outcome, the product.

JOHN HOCKENBERRY: Do you think genetically modified foods and crops are well regulated in the United States?

LEE SILVER: In the United States, I think they're well regulated, meaning the unlikelihood that something will reach the commercial market that is harmful to people, I think yes, in that sense, they're well regulated.

JOHN HOCKENBERRY: Mardi? Are you satisfied with the regulatory process as it exists now?

MARDI MELLON: I'm not satisfied with the regulatory process as it now exists. I think it is fundamentally ill conceived. It's far too voluntary. The FDA regulations really require nothing of any company in terms of providing evidence to the government before a product goes on the market to establish whether it is one of the safe products of biotechnology or perhaps one of the few--and I agree that they're not likely to be many--that's not safe.

LEE SILVER: The regulations are based on agency mandates that existed before biotechnology matured into what it is today, and I think that they can all be brought together in a way that's much, much less cumbersome.

JOHN HOCKENBERRY: So far, we've been talking about food from genetically modified plants, but what about animals? The U.S. doesn't have specific regulations for GM animals. You won't find any GM salmon at the fish counter yet or hamburger at the meat case or bacon either. Canadian scientist Cecil Forsberg has been working for years to market his ““Enviropig”s.” They would have a tough time getting to market in the U.S., because they've been engineered using e-coli. In Canada, GM animals are called "novel foods," and even there, the ““Enviropig” have been stuck in the pen. The DNA Files producer Brian Mann has the story.

BRIAN MANN: A mile outside of Guelph, Ontario, the tree lined streets give way to fields and stretches of wood. Microbiologist Cecil Forsberg points me down a gravel drive towards what looks like a modern industrial farm.

CECIL FORSBERG: You make a left turn. I'd stay away from the front door where your vehicle can pick up the smell.

BRIAN MANN: It's a rental. So I don't mind the smell. [Cecil laughs.]

BRIAN MANN: We park a safe distance away. Despite the wind, there is an odor--cows and mowed grass, but overwhelming it all, the sickly sweet stench of pig manure. Forsberg opens the door to a sprawling barn operated by the University of Guelph. The building is part pigsty, part high tech laboratory. Massive fans churn constantly, maintaining the temperature and easing the odor. Pigs are famous for eating a lot, and it turns out they're not very efficient at digesting the kind of corn and soybeans that make the cheapest livestock feed. As a consequence, their poop is thick with undigested waste products, including phosphorous. For 11 years, this has been Cecil Forsberg's obsession.

CECIL FORSBERG: We thought this would be an ideal project to undertake, because of the extensive phosphorous pollution one finds within areas where there's very intensive livestock production.

BRIAN MANN: The phosphorous problem is a conundrum of modern agriculture. As the human population grows, we require more and more food. That means more cows and pigs, which industrial farmers have supplied pretty handily. But the side effects of those huge factory farms can be devastating.

MARY WATZIN: Oh, we have a creme de la creme spot. We're right on the waterfront in Burlington.

BRIAN MANN: Mary Watzin is director of the Rubinstein Ecosystems Science Laboratory on Lake Champlain. The lake is beautiful, a huge craggy waterway that cuts between Vermont, New York State, and Canada. But phosphorous run-off from large pig and dairy farms has triggered disgusting algae blooms.

MARY WATZIN: You wouldn't miss it, if you saw it. The water looks like there's green stuff in scums on the surface.

BRIAN MANN: Algae can create conditions that gobble up a lake's oxygen, Watzin says, suffocating fish, and throwing the natural ecology into a tailspin. In recent years, toxic concentrations have risen, and several animals exposed to the algae have died.

MARY WATZIN: There are two toxins, actually, produced in Lake Champlain. One is the neurotoxin or brain toxin, and that's been responsible for most of the dog deaths.

BRIAN MANN: Half a dozen dogs have died, Watzin says. The other toxin found during autopsies destroys liver tissue. No humans have been affected so far, because the algae looks so gross that people won't go near it. But a lot of towns along the shore still draw their drinking water from the lake, and as industrial agriculture spreads around the world, producing more and more phosphorous, Watzin says precious water sources are gumming up with this algae soup, which brings us back to Cecil Forsberg's “Enviropig”.

Forsberg wades into a pigpen, waist deep in what looked like everyday Yorkshires, pale skinned, rubbery nosed pigs. The unique thing about these animals isn't their voracious appetites, but a genetic modification with their salivary glands. Remember how pigs aren't very good at digesting the phosphorous in corn and soybeans? Well, it happens that some bacteria are great at it. They naturally produce an enzyme that dissolves the phosphorous.

Forsberg's team managed to introduce this clever enzyme from the bacterium into these animals. They even managed to arrange the DNA so that the gene is expressed in the pig's salivary glands. So when an “Enviropig” munches corn, the enzyme in its saliva digests the phosphorous. As a result, Forsberg says, the “Enviropig” produces 60% less phosphorous than a normal pig. That's twice the reduction that farmers achieve even when they use better and more expensive grains, and when they feed their pigs costly dietary supplements. Even better, Forsberg says, these pigs seem normal in every other way.

CECIL FORSBERG: Although we haven't eaten any of the pork--in fact, it's illegal until there's regulatory approval--I am 99.9% confident that the flavor of the pork from these pigs will be equivalent to that from conventional pigs.

BRIAN MANN: But there's a wrinkle. Pig farmers in Ontario helped to fund the first round of “Enviropig” research, but the project still faces years of testing and regulatory hurdles, and the big grants from an industry group called Ontario Pork have dried up.

CECIL FORSBERG: I'm embarrassed to admit it, but we have no genuine commercial interest in these pigs.

BRIAN MANN: Could I have a ham and swiss? Actually I'd rather have a BLT, please.

BRIAN MANN: After touring the farm, he takes me to a Tim Horton's restaurant. The fast food chain is everywhere in Canada, one more link in our industrial food economy. Forsberg looks around at the crowd grabbing a quick lunch. As the world's population grows, so will our hunger for those BLT and ham sandwiches, which means more pigs, more polluted waterways, and more toxic algae blooms.

CECIL FORSBERG: I don't view this scientific advancement as being one to increase the quantity of food. I view it as a trait within an animal that reduces its environmental impact. Sustainability, I think, is the key issue, which I would raise.

BRIAN MANN: For The DNA Files, I'm Brian Mann.

JOHN HOCKENBERRY: “Enviropig”. This gives new meaning to the term "green eggs and ham." I mean, you've got a pig that helps the environment. You can have your bacon. Come on, this sounds like a great idea. Lee?
LEE SILVER: I think it is a great idea.

JOHN HOCKENBERRY: Mardi? Come on, you've got to be pro “Enviropig”, right?

MARDI MELLON: I'm underwhelmed by the pig. I'm definitely pro environment, but before I signed on to this one, I wanted to know what impact it might have on the pig, and then I'd want to see what the alternatives are. Is it possible to just adjust the feeding ratio of how much corn to other components of the food, and reduce phosphate that way? The other thing I'd want to look at is the system. Concentrating so many pigs in such small spaces and ask if we couldn't think about environmental benefits that we might achieve by changing the system.

JOHN HOCKENBERRY: So the “Enviropig” might help reduce pollution, and genetically modified crops are supposed to ease the farmer's work load. But what's in this genetic engineering for us, consumers? Scientists are trying to create cows that will have more marbling in their beef. That's for us. They're developing soybean oil that's lower in trans fats, allergy-free peanuts, and gluten-free wheat, and for people who just want a good cup of--get this--decaffeinated coffee, DNA Files producer Julie Grant tells us about scientists who are genetically modifying coffee plants to grow without caffeine.

JULIE GRANT: If you want to know the best ways to grow, roast, and serve coffee, or if you just want a really good cup, this is the place. It's the Specialty Coffee Association of America's annual conference. This year, it's at the Long Beach Convention Center in California. The center floor is lined with row after row of more than 500 vendors, looking to buy and sell their gourmet coffee goods. Some are showing off different beans they grow--a rainbow of pale greens, caramel colors, and deep browns. Some vendors are displaying huge stainless steel roasting machines, and others are serving up coffee--drink after drink after drink. It's enough stimulation to make you reach for a decaf--that's unless you're wary of the chemicals used to decaffeinate coffee beans.

JOSEPH RIVERA: We're going to talk about what goes on with roasting --

JULIE GRANT: Joseph Rivera is director of science and technology for the Coffee Association. He's teaching a class in decaffeination. Here's how it works. The green beans are steamed to soften and swell them. Then they're mixed in big stainless steel chambers with solvents.

JOSEPH RIVERA: It's just kind of a big laundry mat, if you will. Things are being mixed up and swirled around.

JULIE GRANT: During all of that swirling, the caffeine molecules separate from the beans and attach to the solvents. They're siphoned out of the chamber, and what's left inside are the decaffeinated beans.

JOSEPH RIVERA: You have to realize that these beans have gone through a lot. They've been stressed out. They've been steamed. They've been beat up in these containers. They've been subjected to chemicals.

JULIE GRANT: Rivera says the chemical used in 60% of coffee decaffeinated in the U.S. is methylene chloride, the same stuff used in paint strippers and degreasers.

JOSEPH RIVERA: People don't like to hear that. [laughs] They don't like to hear that it's in paint remover. It's used in a number of different things.

JULIE GRANT: And Rivera says there's no denying that once you change the chemical make-up of the beans like this, you change the flavor of the coffee. That's where one scientist walking around the coffee conference sees his opening.

JOHN STILES: I'm John Stiles. I'm chief scientific officer for Integrated Coffee Technologies.

JULIE GRANT: What is Integrated Coffee Technologies?

JOHN STILES: We're a small--I guess you'd say a boutique biotechnology company that focuses on coffee and a few other tropical crops.

JULIE GRANT: Stiles says he prefers regular coffee to the decaf on the market today, including the decaf that's processed with water.

JOHN STILES: There's some really good methods for decaffeinating coffee now, but all of them change the flavor. There's no method that can take out just caffeine. You're never going to have the full flavor we all really love about really good coffee using a chemical process to take out the caffeine. Our approach--well, let's just not make caffeine, have everything else the same.

JULIE GRANT: Apparently, it's not as easy as it sounds. So far, it's taken more than 15 years of development in the lab. Stiles grinds up the leaves of the coffee plants and extracts strands of a plant's DNA. From that, he says they've been able to locate the one gene that begins the plant's process of making caffeine.

JOHN STILES: We take the gene, and sort of turn it around backwards, and make it work in reverse.

JULIE GRANT: Normally, that caffeine-making gene sends out what's called messenger RNA, which goes from the nucleus into the body of the cell. There it's translated into the key enzyme that starts the caffeine making process. Flipping the gene around stops the process.

JOHN STILES: And so the enzyme doesn't get made. No enzyme, it can't do that first step, so no caffeine can be made.

JULIE GRANT: Stiles hopes to plant his decaf coffee trees in the field next year, and that's the next step in getting them approved for market. For The DNA Files, I'm Julie Grant.

JOHN HOCKENBERRY: No one knows yet whether coffee connoisseurs will go for the GM decaf. If it gets to market, it may go the way of the “Flavor Save” tomato, which only lasted about three years. But as long as GM crops like corn and soybeans make life easier for farmers, they'll keep turning up in the form of high fructose corn syrup and other additives on the supermarket shelves. It's the cost benefit analysis for farmers though that may be in for a change, as evidence emerges that GM groups may be creating a problem. If you use a chemical weed killer on your lawn, you may have noticed the ingredient, glyphosate.

MARK LOUX: Glyphosate may be the best herbicide we've ever had to work with.

JEFF STACHLER: Glyphosate is the best herbicide ever discovered.

JOHN HOCKENBERRY: Jeff Stachler and Mark Loux are specialists in weed science at the Ohio State University. They love glyphosate, because it kills nearly everything green. Even Charles Benbrook, chief scientist for an organization called The Organic Center in Oregon thinks it's not a bad weedkiller.

CHARLES BENBROOK: It's not acutely toxic. It has not been shown to cause cancer or birth defects. It breaks down fairly quickly in the environment to benign chemicals.

JOHN HOCKENBERRY: Lots of companies sell products with glyphosate. Monsanto's brand is called Roundup. The company also created genetically altered seeds. The seeds grow into plants that can survive Roundup. This is called the Roundup Ready system. Ohio State's Jeff Stachler says the Roundup Ready package is supposed to make work easier for farmers. They can spray glyphosate all over a field. The weeds die; the crops live.

JEFF STACHLER: It's a very good system.

JOHN HOCKENBERRY: Which brings us to where we are today. Stachler and Loux are walking through a field of yellow flowers as high as their shins, weeds. The yellow flowers are Cressleaf Groundsel. They're mixed in with Giant Ragweed. The owner of this Ohio soybean farm contacted Stachler and Loux in 2004, because his weedkiller didn't seem to be working any more.

JEFF STACHLER: One of the things we want to determine is whether these plants are truly surviving from the glyphosate.

JOHN HOCKENBERRY: The scientists sectioned off part of the field and planted 1,400 pink flags, each marking a Giant Ragweed plant. They sprayed the area with glyphosate. Stachler says it killed all the Cressleaf Groundsel, but what about the Giant Ragweed?

JEFF STACHLER: You can see that this plant here that was flagged is dead. There's some others around it that are dead, but if we take a look at some of these others, and some that were flagged, you can see that they are still alive.

JOHN HOCKENBERRY: Stachler says that this was the only farm in Ohio reporting glyphosate resistance in Giant Ragweed in 2004. By the end of the 2006 growing season, they'd confirmed sites in ten Ohio counties. That doesn't surprise Charles Benbrook. Before he came to The Organic Center, he headed up the National Academy of Sciences board on agriculture.

CHARLES BENBROOK: Farmers typically rotate soybeans, cotton, and often corn, but in recent years, it's been Roundup Ready soybeans followed by Roundup Ready cotton followed by Roundup Ready corn, back to Roundup Ready soybeans. Well, obviously those weed populations were getting hammered year in and year out with a single herbicide active ingredient.

JOHN HOCKENBERRY: But all that glyphosate favors the growth of those few weeds that aren't susceptible to the chemical. The next year, those weeds have more seedlings. When the farmer applies more Roundup, those weeds do well again. And so they have even more seedlings and so on and so on until we're looking at a field full of weeds.

JEFF STACHLER: It's the same way with antibiotics or anything. When you do the same thing over and over again and take the easy way out, Mother Nature's going to find a way to combat that, and that's really what we're dealing with here. It's no different from any other type of resistance. We've just done the wrong thing too long, and we need to do more things.

JOHN HOCKENBERRY: There are now seven weeds in the U.S. that have become glyphosate resistant, and according to USDA data, in the last ten years farmers are reacting by spraying the chemical more often, almost doubling the amount they spray on each acre. But Monsanto's Eric Sachs says weeds become resistant to any herbicide that works well and becomes popular.

ERIC SACHS: It still controls more than 100 weeds, and that's why farmers continue to use the Roundup Ready system even though they do face some resistant weed problems in some areas in the United States or other parts of the world.

JOHN HOCKENBERRY: Sachs and other GM proponents argue that these technologies will become more and more important. We'll tell you why in a moment, when we return with The DNA Files.

...
JOHN HOCKENBERRY: Welcome back. You're listening to The DNA Files. I'm John Hockenberry. Our show today is called, "Designing the Garden: Food in the Age of Biotechnology." One of the biggest claims made in favor of genetically modified foods is that they can offer better diets to people in the developing world. Eric Sachs is chief of the global scientific affairs group at Monsanto.

ERIC SACHS: We will be able to make crops more nutritious. We'll also be able to increase the productivity of those crops by helping to resist not only diseases, pests, and weeds, but also to help them resist drought and temperature stress, and salt stress, and other conditions that limit the development of crops in different areas around the world. So I think in 10, 20, 30 years, we'll see agriculture much more productive. We'll see the food crops being developed more nutritious and healthier for us, and in the end, hopefully we'll be seeing a reduction in people around the world that are hungry, because there's more healthy and prevalent food available to feed the world.

JOHN HOCKENBERRY: Sachs is talking about the future, but genetically engineered crops have been around for more than a decade. Have any of them begun to live up to this potential? And if the answer is no, why not?

Let's take one example, rice, the staple crop of hundreds of millions of people around the world. Plant geneticist Ingo Potrykus grew up struggling in postwar Germany, and had to steal food to survive. That's one reason why he set out more than 15 years ago to create a rice plant, which would help nourish people in poor countries. He wanted it to be fortified with beta-carotene, an essential nutrient that our bodies convert to Vitamin A. Without it, people can go blind, and even die. This isn't a big problem in the U.S. We've got lots of nice orange vegetables--carrots, sweet potatoes, along with leafy greens that provide beta-carotene. But around the world, 250 million preschool children don't get enough Vitamin A. Potrykus began to look at rice plants, which already make beta-carotene, but only in the outer green stems, and leaves. He says the grain, the part we eat, also has genes for beta-carotene, but they're turned off. Funded by the Rockefeller Foundation, he spent most of the 1990s figuring out how to turn them on.

INGO POTRYKUS: And you can imagine a staircase of, say, ten steps, and four of these steps were not there. So we had to rebuild these four steps. For this purpose, you need four enzymes, and for these enzymes, you need four genes.

JOHN HOCKENBERRY: Potrykus and his team took the genes from a daffodil and from a soil bacterium. After more than seven years of work, they were making rice that was slightly orange in color, an outward sign that the grain was now producing beta-carotene. They called it "Golden Rice."

INGO POTRYKUS: Golden Rice, when it could be used, could save millions of lives, and prevent blindness in hundreds of thousands of cases.

JOHN HOCKENBERRY: Potrykus and his colleagues were hailed for their breakthrough, but it's been another seven years since then, and Golden Rice still isn't available in developing nations. DNA Files producer Julie Grant traveled to India to find out why.

JULIE GRANT: Just a few minutes drive outside the southern Indian city of Madurai, the crowded streets of food vendors, auto rickshaws, and cars give way to small villages and green countryside. It's a patchwork of farm after farm. There are no barns or outbuildings. There's hardly any tractors. People here do most of their farm work by hand. 77-year-old Dr. Lakshmi Rahmathullah has been working with people in these villages for most of her career. Today, she's gathered some of the children in Arasakulam village. Six-year-old Karthik Kumar bravely walks to the front of the group as an adult holds his head steady for Dr. Lakshmi.

DR. LAKSHMI RAHMATHULLAH: If you look at his eyes, you will see brownish folds on the white part of the eye, which shows that is an indication of Vitamin A deficiency.

JULIE GRANT: Another child here, a 10-year-old girl said she couldn't see at night. She said it was scary. Everyone looked like ghosts. These symptoms, if left untreated, can lead to much worse problems. Her cornea could have literally shriveled away, leaving her totally blind. But the kids here were lucky. They got high dose Vitamin A supplements. This 10-year-old girl got her eyesight back within four months.

International aid organizations estimate that fully a third of children under age 5 in India and Southeast Asia have some level of Vitamin A deficiency. Anand Lakshman is manager of Child Survival Interventions for an aid agency called The Micronutrient Initiative with an office in New Delhi. He says Vitamin A deficiency can lead to diarrhea and make otherwise minor illnesses into life threatening problems.

ANAND LAKSHMAN: So we are looking at the ultimate objective of are we able to impact on child mortality? Are we able to reduce child mortality down to numbers which are far lower than the kind of absolutely unimaginable numbers that we have today.

JULIE GRANT: About two-thirds of Indian children under age five get Vitamin A supplements. They line up twice each year at health clinics to receive a spoonful of the serum. A mega dose of Vitamin A is stored in the child's liver, and is slowly released through the months. Lakshman says it's reduced the child mortality rate 23%. But there's debate in India over the need to continue the supplementation program. Dr. HPS Sachdev is former president of the Indian Academy of Pediatrics. He's a small man in a dark blue turban. Sitting in his medical office, he says most children these days don't need the mega doses

DR. HPS SACHDEV: I view it as a medicine. God did not intend us to take a pill off and on.

JULIE GRANT: Sachdev says many Indian families have gained the education and financial means to meet their Vitamin A needs the way people in richer countries do--through those orange vegetables and leafy greens. So children should only get the mega doses if there's an obvious lack of Vitamin A in their diet. Sachdev says there's another way to meet low level needs - golden rice. That's the rice genetically engineered to express beta-carotene. Sachdev says children could just eat a little rice regularly.

DR. HPS SACHDEV: A small lower dose mimics the daily requirements or is much closer to the daily requirements and its chances of toxicity are much lower as compared to a huge pill based on the mega dose approach.

JULIE GRANT: Ten years ago, Dr. S.R. Rao, director of India's department of biotechnology, was touring laboratories in Switzerland, and met geneticist Ingo Potrykus. Potrykus was still experimenting then, trying to make rice express beta-carotene. Rao says he wanted that rice for India, because he thought it could go a long way to reduce Vitamin A deficiency in regions where rice is a staple in the diet.

DR. S.R. RAO: So I'm from the southern part of India, and we only eat rice and rice and rice.

JULIE GRANT: Rao says they often eat rice for breakfast, lunch, and dinner. But why would farmers in India want to plant Golden Rice? Dr. Rao is a leader in efforts to transfer the genes for Golden Rice into varieties Indians already eat. Dr. Rao takes us to what's called a phytotron. It's a building used to grow plants, but it doesn't receive natural light like a greenhouse. That sound is a sterilizer. Before you enter the phytotron, you've got to spend a couple of minutes in this chamber. It blows super high air pressure to clean off contaminants that could ruin the experiments.

DR. S.R. RAO: To really get clear of your dust and all the organisms and you just come to this side. Now they're coming out. Okay? So Julie's smiling, that you are sterile, Julie.

JULIE GRANT: Sterilized. He means sterilized. It's just air.

DR. S.R. RAO: Sterilized. Yeah, that's the correct thing. [laughs] I am sorry. You are sterilized.

JULIE GRANT: The phytotron's main room has row after row of huge aqua colored refrigerators that keep the young plants at a constant temperature. Inside are Indian hybrids of Golden Rice. The genetic modification, the beta-carotene, was originally bred into a Japanese rice variety. Rao says in his phytotron they bred the Golden trait into some popular Indian varieties.

DR. S.R. RAO: That is in terms of their yield, in terms of resistance to diseases and pests. Such varieties have been taken, and where we put this traditional trait of Golden Rice.

JULIE GRANT: So traits that farmers like?

DR. S.R. RAO: Traits farmers like.

JULIE GRANT: Because they're going to grow better. They're not going to have as many pests.

DR. S.R. RAO: Yes, exactly.

JULIE GRANT: What he expects farmers to like even more is that the government plans to give Golden Rice seeds free to those making under $10,000 a year. This is possible, because of a deal struck between Ingo Potrykus, the scientist who created Golden Rice, and the seed company, Zeneca. There are some 70 patents on the various technologies involved in making Golden Rice. Zeneca, which is now part of Syngenta, owns many of those patents. The company was interested in selling Golden Rice to the U.S. and European health food markets. So in exchange for the right to do that, the company agreed to give the seeds away free to developing nations. But those free seeds are making some people angry. Vandana Shiva is famous worldwide for her opposition to genetically modified foods and the companies that pervade GM seeds. She calls Golden Rice a hoax, and says there are more natural ways for Indians to get Vitamin A.

VANDANA SHIVA: You can add a few micrograms of Vitamin A to a white, polished rice, and be thrilled that you have added nutrition. But again, food is not just rice, and definitely for anyone who has even a kindergarten knowledge of nutrition, polished rice is not where you turn to for meeting your Vitamin A needs. You turn to your greens. You turn to your coriander, your curry leaves, something very, very central to our eating.

JULIE GRANT: 60% of Indians are farmers, but many don't grow food for themselves any more. Ever since the Green Revolution brought pesticides and fertilizers to India in the 1960's, Shiva says farmers have been growing cotton and rice for the commodities market instead of food for their families. She says they need to be reeducated to grow and eat those leafy greens and other vegetables rich in Vitamin A.

But farmers aren't unified in what will be the best future for Indian agriculture. Some are clamoring for the latest technologies. There's a black market for genetically modified cotton seeds. But other farmers and activists agree with Shiva. Last year, GM opponents convinced the Indian Supreme Court to temporarily ban any new genetically modified crops from being planted, saying the crops were bad for human health and the environment. The ban has since been lifted. Some farmers worry GM crops could destroy their export market.

Northern India in the shadow of the Himalayas is the main world region for growing basmati rice. Basmati is a huge export crop for Indian farmers. Gurnam Singh is leader of the BKU Farm Union in this state, Haryana. Last year, he got wind that one of the multinational biotech companies had planted an experimental plot of genetically modified rice in the midst of the basmati region. Today, he rides up to that plot on his motorcycle, but there's no genetically modified rice here any more. Singh rallied a group of farmers, at least 100 by some counts. They piled straw over the small test site, poured some kerosene, and basked in the heat of the message they were sending to Monsanto.

GURNAM SINGH: (In Punjab)

TRANSLATOR: He's saying they met here basically as a sign of protest towards the company, because they were doing something--something which would harm the farmers, and so basically this was supposed to be a sign of protest for them by burning.

JULIE GRANT: That same day, Monsanto telephoned Dr. MS Swaminathan to tell him what had happened. Swaminathan is largely credited for bringing modern farming to India in the 1960s, and for leading efforts to bringing genetically modified crops here today. But when he heard farmers had burned the GM rice plot --

DR. MS SWAMINATHAN: I was happy, because I thought it was wrong.

JULIE GRANT: He says the company shouldn't have planted genetically modified rice in India's basmati rice region, because of the possibility of cross-pollination.

DR. MS SWAMINATHAN: It was foolish to have gone there, in the heartland of the rice exporting region, basmati rice, because we all know genetic pollution, gene flow, genetic contamination.

JULIE GRANT: Swaminathan says contamination could ruin India's rice trade with Europe, Japan, and other countries that don't accept genetically modified imports. But he says there are many places in India where genetically modified crops do make sense, and will be necessary to grow enough food for India's growing population.

DR. MS SWAMINATHAN: Genetic modification is one more tool, which can help you to overcome certain problems.

JULIE GRANT: He remembers when his family couldn't get rice. It was rationed by the government. People were asked to fast one day a week, because there wasn't enough food in India. He says it's time for the government to make policies that will provide enough food.

DR. MS SWAMINATHAN: Why, because we've got 1.1 billion people today--it will be 1.5 billion--the largest population in the world. Who is going to feed us? A country like India cannot depend on others to feed this population. And I think it's the fundamental duty of a government to ensure the daily bread to everybody.

JULIE GRANT: If Syngenta is serious about giving away Golden Rice for free, Swaminathan says it should drop its patents. Syngenta says poor farmers in India will never have to pay for Golden Rice, but the company may want to use the technology elsewhere. So it's holding on to its patents.

There are also questions about how much it will cost to complete development, to distribute seeds, to ensure children actually eat it, and that it provides enough Vitamin A. Back in Araskulam Village in southern India, Dr. Lakshmi Rahmathullah wouldn't mind seeing Golden Rice on these small farms, but she says for the sake of its children, it's too soon for the Indian government to stop offering Vitamin A supplements.

DR. LAKSHMI RAHMATHULLAH: There is no best solution. Offer families fortified rice, offer families fortified salt, offer families Vitamin A solution. Multiple solutions are the best answer.

JULIE GRANT: Dr. Lakshmi says the most important thing to offer malnourished families is food they can afford. For The DNA Files, I'm Julie Grant.

JOHN HOCKENBERRY: You know, in India, some people greet visitors to their home by placing a smear of rice mixed with turmeric on their forehead. It's a sign of respect and welcome. In all cultures, there are different ideas about what is sacred, about the meaning of food, and what it symbolizes. So the debate over genetically modified food is informed by culture, our values and beliefs as well as by science. That's true for all of us, including our scientists, Mardi Mellon and Lee Silver, who with their very different viewpoints helped us navigate the debate over GM foods. Hey, what kind of foods do you guys eat, by the way? Lee?

LEE SILVER: I could answer it very quickly. I only eat inorganic food.

MARDI MELLON: And I am a strong supporter of organic agriculture as a scientifically advanced vanguard of the kind of agriculture I think we're going to need if we're going to deal with global warming in the future.

JOHN HOCKENBERRY: I'm not hearing hot dogs and Twinkies on your table. Am I right about that? Mardi?

MARDI MELLON: You're right, but someday, I hope Lee and I can sit down and have ourselves a nice cup of strongly caffeinated coffee.

LEE SILVER: Fair trade.

MARDI MELLON: I'll buy.

LEE SILVER: That's right.

JOHN HOCKENBERRY: We'll hold you to that. I'm John Hockenberry. Thanks for listening to The DNA Files.

To find out more about genetically altered food, 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, "Designing the Garden: Food in the Age of Biotechnology" was produced by Julie Giant and Elizabeth Kulata. The field producer in India was Adam Burke. The DNA Files is managing editor, Loretta Williams, editor, Deborah George, science content editor, Sally Lehrman. Research director is Adi Gevins. Production support by Noah Miller, Julie Caine, and 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 Conrad Praetzel and Robert Powell. Marketing of The DNA Files is by Schardt Media. Legal services by Cooper, White and Cooper, and Spencer Weisbroth. Special thanks to Murray Street Productions. Send your responses and letters to feedback@dnafiles.org. For CDs and transcripts, call 888-303-0022. That's 888-303-0022. The executive producer is Bari Scott. This has been a SoundVision production.

The DNA Files:
Unraveling the Mysteries of Genetics

As heard on National Public Radio

Beyond Human

Hosted by John Hockenberry

Transcript

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

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

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

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

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

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

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

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

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

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

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

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

GIRL 4: Probably like 80 or 90?

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

GIRL 4: Yeah.

JOHN HOCKENBERRY: What do you think?

GIRL 5: 75, 80%.

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

GIRL 6: Yes, we are sitting down.

JOHN HOCKENBERRY: 99%.

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

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

GIRL 8: Ouch.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

SEAN CARROLL: How is it that the head is put at the right end of the animal, and you get the right number of digits, and you get this beautiful bilateral symmetry that exists in a lot of animals?

I don't think any biologist is sort of immune to that wonder at how a single fertilized egg becomes a complete complex individual with all of its body parts. And this process we refer to as development or embryonic development.

So only a small fraction of all the genes in our genome are devoted to body building and organ building and sort of the patterning of the way we look. You can sort of think of them, if you want, metaphorically speaking, as the sculptors and painters in our genome. And over the course of a couple of decades, developmental biologists have defined what we call a genetic tool kit for development. It's changes in this tool kit that underlie the diversity of everything we see. A lot of what's going on in evolution is we're just changing the number and identity of particular body parts.

So once sort of making vertebrae was figured out, it's just tinkering with the number of vertebrae or the identity of vertebrae or what's sort of erected on that sort of chassis, and that would be true, whether we're talking about snakes versus humans or even humans versus chimpanzees. You know, the anatomical resemblance between ourselves and the chimps is pretty obvious, but you know, we've got bigger brains, different facial shape, different arm length, and these are really perceived as minor tweaks of anatomy. We're just a remodeled ape, I think. That's what I boil it down to. And this process of remodeling involves using these genes in either slightly to dramatically different ways in the course of evolution.

So it's demystifying a lot of what we found mysterious about biology and about evolution by making lots more connections between the simple and the complex, and this is what we can do through genomes, and this what we can do through developmental biology. We can trace the origins of structures. We can trace the relationships among structures, and we can see all sorts of gradations from really very, very, very simple versions of some structures to what we think is, you know, the more complex grand versions that we carry. So we're finding much more in common with the whole animal kingdom than we ever thought before. And you know, humans wanted to hold themselves out as something unique. Well, the more you look at the genetics, the less unique we are. You know, we don't even have more genes than a puffer fish. So you know, you're just going to have to get over that.

JOHN HOCKENBERRY: So 99% similarity. What does that say to you?

BOY 1: Well, for how much we have, 1% is still a lot.

JOHN HOCKENBERRY: What do you think?

BOY 2: Chimps and their DNA, all of it, all of their chromosomes, it's 1% different. But you have to realize that not all of the DNA actually controls something. A lot of it's just left over from whatever. So in that 1% that's different could be a lot of stuff that controls traits and the brain size and the body hair and the body structure and --

ROSS HARDISON: [laughs] If you try to talk about a percentage human or a percentage chimpanzee, that's a hard thing to define. There's no reason to think that every nucleotide or every base pair in the human genome is important in making you human. It is possible, maybe way more than half of the DNA in our genomes is doing nothing. So what does it mean, if 98% of something that doesn't do anything [laughs] lines up? Right? That's not such an interesting question. The interesting question is: What's different?

JOHN HOCKENBERRY: One clue can be found in our genes. Researchers have found that chimps do share almost all their genes with humans, but they work differently.

ROSS HARDISON: When they see genes whose coding sequences are substantially more different than you would expect, we say, "Well, wow, maybe this has something to do with making humans uniquely human or making chimps uniquely chimp."

GIRL 1: Their eyes are like exactly the same as ours -- the same shape and the same flat face, and 10% of like communication is only words, like only 10%. So it's all about body language and how you act.

JOHN HOCKENBERRY: What do you think the chimps are thinking? Do you think if they knew that you'd actually pay money to watch them stand around? [laughter]

GIRL 2: They probably think we're weird. [laughter]

GIRL 3: And they're kind of like -- they're probably wondering, just like we are, like, "What are they doing?" and like "How do they live?" and stuff.

BOY 2: We're just a little bit more advanced with the speaking, but they can do sign language, which a lot of people can't do.

WILLIAM FIELDS: Here comes Liz. Come up here and talk on this keyboard, okay? Come tell the visitor what you said. So is there anything you would like after the Wasserman test, Panbanisha?

COMPUTER: Coffee.

WILLIAM FIELDS: You'd like some coffee? You would?

JOHN HOCKENBERRY: Coming up, we talk to the animals, and evolve an eye. You're listening to The DNA Files. We'll be back in a minute.

FIELDS: All right. So -- all right.

...
JOHN HOCKENBERRY: This is The DNA Files. I'm John Hockenberry. That's a bonobo, one of the chimpanzees genetically most similar to humans. As our bright young students mentioned, there are some pretty big differences between chimps and us. For example, my human DNA has given me the ability to talk, which is why I can host this program. [laughs] Digging around in genomes may one day help us explain how language works, but to get a better picture now, we first need to widen our view.

WILLIAM FIELDS: Come up here and talk on this keyboard, okay? Come tell the visitor what you said.

JOHN HOCKENBERRY: At the Great Ape Trust, just outside Des Moines, Iowa, researchers communicate with bonobos using symbols or lexigrams. The bonobo sits at a large touchscreen. When she presses a lexigram on the screen, the computer speaks its name.

COMPUTER: Coffee.

JOHN HOCKENBERRY: William Fields is director of research and co-author of the book, Kanzi's Primal Language. No one trained Kanzi and his sister, Panbanisha to use the keyboard. They just watched the older bonobos listen to the humans and learned on their own.

WILLIAM FIELDS: This is Panbanisha. She's the real life of genius.

LIZ: Here you go, Panbanisha.

WILLIAM FIELDS: Okay, it's ready. Come do it. Come do it. She's going to match to sample.

COMPUTER: Brush.

LIZ: Good. Do 15 of them.

COMPUITER: Sue, Sue.

WILLIAM FIELDS: The lexigram comes up, and there's spoken English, and then Panbanisha matches the lexigram and the spoken English to the photograph. She gets several selections of photographs there, and she's really good. The only time she's wrong is when she wants to make a point, and she'll just hit one to be wrong. She's never wrong without intention.

COMPUTER: Popsicle, Popsicle.

WILLIAM FIELDS: She learned just the way children learned language. She acquired it just by being exposed to it, and humans using the lexigrams around her.

COMPUTER: Marshmallow, marshmallow.

WILLIAM FIELDS: We're getting ready to test her receptive vocabulary for English. We know it has to be in the thousands of words, and we'll never really know. We'll just have an idea of the dimension, because it's unlimited. I mean, I know that she knows "microphone," because I've asked her to hand me the microphone before, and she's handed it to me. We don't have a lexigram for microphone. Or I can ask her to go over and see the visitor with blond hair. She knows blond hair. We don't have "blond" on the keyboard. She has all kinds of competencies that we're unable to measure at the moment, because of limitations of the keyboard.

LIZ: I know you're upset, but we're not going to do that.

WILLIAM FIELDS: There you go.

LIZ: This is "clippers."

COMPUTER: Clippers, clippers.

LIZ: Do you want me to come in?

WILLIAM FIELDS: Yeah, Panbanisha got mad at us. We got a little too involved in the whole human conversation thing, and like I told you earlier, they enforce the social rules. The best way she could express her frustration with us was to hit the wrong key for "clipper." I mean, we all know she knows "clipper," just like she knows her name. And she hit it twice for us, just so it would make that noise. [laughs]

COMPUTER: Coffee.

WILLIAM FIELDS: Okay, well, I'm going to get the coffee when you're through.

AL: The order's been placed. [laughs]

WILLIAM FIELDS: What are you hanging around for, Coffee Boy? [laughter] A decaf caramel macchiato is a favorite. Panbanisha and I have spent a lot of time in the forest together. We've made stone tools together. We've camped out. We've made fires, drank a lot of coffee together. She's a really good friend. You're doing good. But they're not human. They are persons, but they're not human. They're bonobos. They have identity. They have autobiographical memory. They have episodic memory. They can identify themselves in photographs. They identify themselves in the mirrors. It's not just that they identify themselves. If you have two of them in the mirror, they can point to themselves, and they can point to the other one in the mirror. They know who they are. They have a history, and they can tell you about it.

Humans are wonderful and special, but they're not any more wonderful and special than any of the other Great Apes or the biodiversity on this planet. Even though we have wonderful talents -- or I think that they're wonderful -- that may just be -- that's just a bias. I mean, I happen to like mathematics, but the bonobos don't seem to do mathematics, even though they can do quantity judgments, and they can do numerosity and ordinality. They're not interested in differential equations, but now that I think about it, neither is my mother.

All right. After you do your Wasserman test, we'll have some coffee, okay?

COMPUTER: Coffee.

JOHN HOCKENBERRY: How would you prove to a chimp that you're more advanced or do you maybe think that you're not?

BOY 1: I think it's -- a lot of it that the main argument is language.

JOHN HOCKENBERRY: Language?

BOY 1: They probably do have vocal chords, but just like not --

BOY 2: They don't know how to use them yet.

BOY 1: Not -- it's being developed.

BOY 2: They're probably just not as developed yet.

JOHN HOCKENBERRY: For years, we've assumed that humans have language, because we've mastered abstract concepts like grammar, symbols, and syntax. But we also know that the human voice box, and brain, are built differently than in most other species. So how do we sort out what's happening in our heads and bodies that's different from other animals?

ERICH JARVIS: To actually answer that question, we have to take a comparative genomic approach.

JOHN HOCKENBERRY: Erich Jarvis studies that genes and brains of vocal learners at Duke University in North Carolina. These aren't animals that can talk, but they are animals that learn to make more than the growls and whistles they're born with, animals that communicate by complex vocalizations. You know some of these animals.

ERICH JARVIS: There are three vocal learning groups of mammals at least and three vocal learning groups of birds. Amongst the birds, these are parrots, hummingbirds, and songbirds, and what we discovered is that these vocal learning birds have very similar brain pathways to control their learned sounds. We argue that the bird brain pathways are similar to humans. The mammalian part of the story is similar. In humans, bats, and dolphins, these are all vocal learners, and yet they are separated by vast genetic differences, but yet you have a chimpanzee, a very close relative to the human, 98% identical in its sequence, is not a vocal learner. So we're also doing genomic comparisons on chicken and chimpanzee and bat to ask the question, "Will bats and humans have a similar type of mutation as you find in songbirds, parrots, and hummingbirds?"

DONALD KROODSMA: We're listening now to a song sparrow singing here, and there's a close relative, a swamp sparrow, both in the same genus.

JOHN HOCKENBERRY: Donald Kroodsma has been studying vocal communication in birds for over 30 years. He's one of the best guys on the planet to take us for a stroll in the woods. He likes to be there before sunrise, of course. That's when the birds sing the best, apparently. So imagine it's 5 AM. You're in the Quabbin Reservoir, a wilderness area in central Massachusetts, shh. Here we go.

DONALD KROODSMA: And what's so intriguing about these two -- they're members of a group called songbirds. And songbirds learn to sing like we learn to speak. And I can say that a thousand times, but wow, then I can show you a sequence of my daughter's babbling and how she babbled at a year and a half to two, and that's something that we've all done to get to where we are so we could speak. Then you compare that babbling of that child to the babbling of a baby bird, and it's exactly the same process, because these songbirds have to hear other adults in order to develop normal songs. If they didn't, they'd just sing absolute nonsense. It's like taking a human child and not ever letting it hear language -- why, it would not speak a language [laughs], recognizable a language either.

And then there's -- there's this bird over here. It's an oven bird, singing on the forest floor. And the mnemonic that we read in the field guides is, "Teacher, teacher, teacher, teacher." It's a crescendo. It's just shattering, and our ears just can't capture what these birds are doing. And these songbirds have ears that are a lot better than ours. They can resolve sounds in time far better than we can.

Any small songbird like the winter wren, once you start to slow it down, it develops this richness, because now we're starting to hear the individual elements, and we're lowering it to a frequency where our ears can pick it up. And you take a tiny little 10-gram wren, and slow it down far enough, it starts to sound like a humpback whale.

ERICH JARVIS: All the research that I've been doing in the past 10 years has been leading up to one conclusion for me, that language or vocal learning in general, what's unique about it in those species that have it -- humans, songbirds, parrots -- is the motor skill part of it.

JOHN HOCKENBERRY: Again, Erich Jarvis.

ERICH JARVIS: And the neurobiology of our results are suggesting that the vocal learning pathways, what's unique about them is they're coming out of a pre-existing motor pathway, not in a perceptual one, or one might call a conscious one or something else.

DONALD KROODSMA: Oh, getting these songs right is an extraordinary athletic endeavor. And a friend of mine published a paper many years ago entitled, "Vocal Gymnastics in Wood Thrush Songs," and that really captures it. If you watch a gymnast flipping and turning in the air, and you think, "What did it take to get her t