British Scientist Driven To Find 'Spark Of Life'

September 27, 2012

Guests: Frances Ashcroft – Amy Adams

TERRY GROSS, HOST: This is FRESH AIR. I'm Terry Gross. You probably don't think of yourself as powered by electricity, but you are. Everything we see, hear, think and speak is a result of electrical activity in our nerve and muscle cells. The new book, "The Spark of Life," is about electricity in the human body. The author is my guest, physiologist Frances Ashcroft.

Her 1984 scientific breakthrough involves electricity in the body. She discovered what triggers the electrical impulses that control the secretion of insulin in people who were born with diabetes, a type of diabetes that is very rare. Her discovery opened the door to further research, and now most people born with diabetes can be treated with pills instead of insulin injections.

Ashcroft is a professor of physiology at Oxford University. Frances Ashcroft, welcome to FRESH AIR. So just give a little bit of an overview of a few of the ways that electricity functions in the human body.

FRANCES ASHCROFT: Well, I think one of the most interesting things is that absolutely everything that we see or hear or think or feel or down is down to electrical impulses that are taking place in the nerve cells of our brain and the muscle cells of our bodies so that your ability to hear me now is because there are cells in your ears that are converting the sound waves into an electrical signal, which is what the brain can interpret as sound.

And the person that you are is down to the electrical signals that are occurring in the nerve cells in your brain. So everything is down to electricity.

GROSS: So how does electricity in the body compare to electricity that powers our appliances and our computers?

ASHCROFT: Well, I would say that bioelectricity is similar but not identical to the stuff that's in the sockets. Both are electric currents, and in both cases the electric current is nothing more than a flow of charged particles. But the stuff in our houses is carried by electrons, whereas the stuff in our bodies is carried by irons, salts such as sodium chloride, common salt in other words, the stuff you put on your meat.

The second thing is that the speed is very different. So electricity in wires is carried at the speed of light, which is around 186,000 miles a second, whereas that in our bodies is very, very much slower.

GROSS: So you've done groundbreaking work about neonatal diabetes, people who are born with diabetes. It's a relatively uncommon form. But your breakthrough relates to electricity. So could you just describe how electricity functions in this form of diabetes?

ASHCROFT: So let me begin by saying this is an extremely rare form of diabetes. It's not at all related to juvenile diabetes, which is the problem that's normally found in children. This is a rare form where you're actually born with the disease. But what's been marvelous about this is that having identified the cause of it, we've been able to offer a different therapy for people who are born with this disease.

Diabetes happens when you have too high a blood sugar concentration, and that usually happens because you don't have enough of the hormone insulin, which is the only hormone which can lower your blood sugar concentration after a meal. So every time you eat a Mars bar or a Hershey bar, what happens is your blood sugar level will go up, insulin will be released from the pancreas, and that will cause the blood sugar to be lowered. This doesn't happen in diabetes.

And what I was interested in understanding is how the rise in the blood sugar causes insulin to be released from the pancreas. And it turns out, this is what I discovered late one night, you know, that this is down to a whole complex series of events, but one of the crucial events, the little bit in the jigsaw puzzle that I discovered, is a protein that acts like a tiny hole in the cell membrane.

And when this little pore is open, irons can go through it. So they carry in this case an electric current. And when the pore is shut, the irons can't go through. And the movement of the irons triggers a series of events that influences whether insulin is secreted or not. So very simply put, when the pore is open, insulin is not released, and when the pore is shut, insulin is released.

And glucose, or the rise in blood sugar, stimulates insulin secretion by closing these tiny pores. And what we found, together with a wonderful colleague of mine, Professor Andrew Hattersley, is that mutations, genetic defects, in the gene that makes this tiny pore cause it to be always open. So of course no insulin is ever released.

GROSS: Now, how does this relate to electricity?

ASHCROFT: Ah, it relates to electricity because the current that flows through those tiny pores, those channels, which is what we call them, is actually an electric current. It's just that this time it's carried by potassium irons, not by electrons, and it generates electrical impulses in the pancreatic cells, and that's what's necessary for insulin release.

So these cells fire electrical impulses in just the same way as your nerve cells do.

GROSS: And through your research, as a result of your research, now people who are born with this type of diabetes, neonatal diabetes, they can take pills to regulate their diabetes as opposed to self-injecting, and that's an extraordinary change in their lives, thanks to you and your research partners.

When you first made the discovery, what happened in the lab? Just tell us about that moment of breakthrough.

ASHCROFT: Well, of course there were many steps on the way, but the first step, when I actually discovered this particular tiny little pore in the membrane that conducts electricity, it - I was working all on my own, late in the night, about 8 o'clock, I think, and I was looking to see this tiny pore close in response to an increase in the sugar concentration in the solution around the cell.

And so I was recording these tiny little electrical currents and hoping that they'd go away. And when they did go away, I actually thought that there was something wrong with the experiment. I didn't at the time realize that what I had predicted might happen had happened. And so it wasn't until I took the sugar away again and the tiny little current blips came back that I realized actually this was what had happened.

And I was unbelievably excited. I don't think people realize the excitement of being a true discoverer. That's one of the wonderful things about being a scientist. There are no new places to discover on this Earth, but there are many, many new ideas to discover, new things to find out about the way the world works, and to me that's an incredibly exciting thing about being a scientist.

So you can imagine I was over the moon. I couldn't sleep. By the next morning, of course, I thought it was all a mistake.

GROSS: Why did you think that? Why were you ecstatic one day and then you were - you just didn't believe it the next?

ASHCROFT: I think the thing is you always think that you've made a mistake, that something must have gone wrong in the experiment, that this wasn't actually a real breakthrough because breakthroughs happen so rarely, that I'd done something wrong in the experiment.

So you have to do what everybody does who's a scientist and that's repeat the experiment again and again and again, and I was lucky. I was right, and the experiment has been repeated many hundreds of thousands of times by different people throughout the world, and it always is the same.

GROSS: You print in your book something that somebody who told you, somebody who was born with diabetes and as a result of your research can take pills instead of self-injecting insulin, and she says: Thanks to you, I can wear a dress. I no longer need a skirt or trouser waistband from which to hang my insulin pump.

I mean, that sounds like a trivial thing, but that sounds like, on the other hand, it meant so much to her to be able to live life without the encumbrance of an insulin pump.

ASHCROFT: It's not trivial if you think that you're an 18-year-old, and you want to wear a slinky, sexy dress.

GROSS: Right.

ASHCROFT: What do you do with your insulin pump for her prom? She had to strap it to her leg with sort of package tape. That's not very comfortable when you're dancing. So you can see it does matter, and it also matters if you're wearing a pump, and you want to go swimming. You have to take it off and then put it back on again. It's not very nice every time you put the needles in.

Just injecting yourself every day, especially if you're a parent if you've got to inject a tiny baby several times a day, that's not so easy. So I think for them it has actually been liberating. And for me, it's been such a privilege to meet these people. I've been fortunate enough to meet some of the people who Andrew's work and mine has been able to help, and that's been a very, very emotional experience.

It's not usual. Most scientists will never see their work help people in their own lifetime. I've been lucky.

GROSS: If you're just joining us, my guest is scientist Frances Ashcroft. Her new book is called "The Spark of Life: Electricity in the Human Body." Let's take a short break here, and then we'll talk some more. This is FRESH AIR.

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GROSS: If you're just joining us, my guest is scientist Frances Ashcroft, and she is a professor of physiology at University of Oxford in England. She has a new book "The Spark of Life: Electricity in the Human Body." And it's through understanding how electricity in the human body functions that she made her scientific breakthrough, which is discovering what causes neonatal diabetes, that's the form of diabetes that some people are born with because of a genetic defect.

And as a result of her research, people with that form of diabetes no longer have to self-inject insulin. They can just take a pill. So your work in understanding neonatal diabetes had to do with ion channels, these, like, proteins that electricity passes through. And these kinds of ion channels are involved in basically all of our functions in the body. Could you talk about that a little bit?

ASHCROFT: Ion channels are little pores that are found in the membrane, the envelope, around each of our cells. And they're found in every cell of the body and in every organism on Earth, from the smallest bacterium to the redwoods of California. And they're important for everything that we do.

I suppose one of the ways in which ion channels can be seen to be important is by what happens when things go wrong. So your heart is controlled by electrical impulses, which determine the rate at which it beats and ensure that each beat is coordinated so that it functions as a pump.

And these electrical signals originate in the pacemaker area of the heart, and they are down to the activity of ion channels, these tiny pores. And if there are genetic defects in these pores then things go wrong, and you are susceptible to cardiac arrhythmias. And a particular example of this is a disease that goes by the strange name of Long QT Syndrome.

And what happens here is that a particular ion channel doesn't work properly, and the consequences that people with this disease can have a cardiac arrhythmia and simply die as a consequence of being startled or excited or even, in one case, laughing too much.

So there are sad tales of people who've died as a consequence of being too excited, watching a TV show, being told off, dying of fright.

GROSS: So since we were talking about electricity in the heart, why don't you explain the principle of how defibrillators can save somebody who - well, tell us who it can save. And defibrillators are those two pads that you see a lot in crime shows and hospital shows where, like, if somebody's had a heart attack or something, the defibrillator pads are put on the heart, they turn on the button, and there's like shocks that are delivered, and, you know, maybe it saves the person, maybe it doesn't.

But we've all seen that a lot in movies and television and hopefully not too much in real life.

ASHCROFT: Very often what people think is that the heart has actually stopped, and the defibrillator is being used to shock it into action. That's not actually the case. What's happening is that the heart is fibrillating, that's why it's known as a defibrillator. And fibrillation means that the heart is no longer beating in a coordinated, synchronized fashion, which is necessary if it's to act as a pump.

Instead, it's become rather like a quivering jelly. Vesalius once called it a quivering bag of worms. So you can imagine that if that happens, the heart can't work as a pump anymore. No blood is going to come out. And that's the reason you die: because the brain isn't getting any oxygen, and neither is the heart, of course.

So what the defibrillator does is the shock stops the heart, and then the hope is that it will restart automatically but this time in a synchronized fashion.

GROSS: So it's not - it's not unlike your computer crashes, and you turn it off and then turn it on again?

ASHCROFT: It's exactly like that, in a way. It's pressing the reset button. I have to say in Australia they have a wonderful name of packer whackers. And that's because a millionaire philanthropist donated a lot of money to ensure that the defibrillator were carried in every ambulance in one of the states of Australia because he was fortunate enough to be saved by the presence of defibrillator in an ambulance when he had a heart attack.

GROSS: Let's talk a little bit about electricity and pain. Pain signals are communicated with the help of electric impulses, yes?

ASHCROFT: Yes, that's right. So what happens is there are sense organs. Very often these are just pure - just the ending of the nerves in your skin that detect pain, and they detect a signal, and then that's translated into an electrical signal, which is sent up specialized nerve fibers known as sensory nerve fibers to the brain, which then interprets it as pain and enables you to do something about it.

And what is fascinating is that ion channels, these important proteins, are also involved in the sensation of pain. And one of the ones I think is very interesting is an ion channel that goes by the name of TRPV1, and this is very important for detection of noxious heat. So whenever you feel something that's burning hot, this is detected by this particular ion channel.

It's sensitive to heat, and it fires off a signal that goes up your nerve cells. And it's exactly the same ion channels that are stimulated by chili peppers. So the reason chili peppers taste so hot is because they stimulate the same ion channel, and, you know, the brain interprets them both as the same thing.

And interestingly, they have been modified in vampire bats to detect the body heat of their prey. So that's how they pick up the fact that your big toe is sticking out of the mosquito net, and they can come and suck your blood.

GROSS: Does knowledge of how electricity works in sensing and communicating pain, might that lead to breakthroughs in controlling pain?

ASHCROFT: That's certainly hope so that there are a certain number of people working now very hard on seeing if they can find blockers of ion channels that specifically target ion channels found in the sensory nerves. At the moment, every time you go to the dentist, you will have a local anesthetic, and that will numb your mouth so that you don't feel any pain.

But it will also numb the motor nerve fibers that go to the muscle fibers. So not only will you feel no sensation, but you'll also have a kind of paralyzed jaw. And what's happening there is that the drug you're taking, which is usually Lidocaine, actually is inhibiting the sodium channels. It's blocking the sodium channels in both the sensory nerve fibers and the motor nerve fibers, those which feel pain and those which cause muscles to contract.

What people are now looking for are drugs which will only work on the ion channels that are found in the sensory nerve fibers. And happily, there are some ion channels which are specific to the sensory nerves. So in the future, maybe, we can look forward to having an anesthetic which doesn't give us a lumpen jaw.

GROSS: Well, wouldn't that be nice?

ASHCROFT: It would be wonderful. There are unfortunately some poor people who have mutations in some of these ion channels that are specific to nerve fibers, and in some cases these knock out the function, so they can't feel pain at all. And that's really, really a tragedy because unfortunately it means that they can suffer broken bones, they can burn their hands on a hot pan, and they don't notice it. And so they can actually suffer dangerous lesions, dangerous wounds, without realizing it.

And then there are people who have the opposite, and I have no idea which is, you know, which is worse to have because they feel pain much more sensitively. So they are often in considerable pain as a consequence of the fact that their ion channels are operating all the time. And so they get - they say that walking is like walking on hot coals all the time.

GROSS: So what you're saying about ion channels is that it tells us what pain really is subjective in part because of different physiologies.

ASHCROFT: Well, that's actually very true. And in fact some people may indeed be more sensitive to pain, not just these very specialized people but you and I, because there are variants in the gene that codes for this particular ion channel that's found in the general population.

And it looks as though some of them actually enhance sensitivity to pain in some people and reduce it in others.

GROSS: Frances Ashcroft will be back in the second half of the show. Her new book is called "The Spark of Life: Electricity in the Human Body." I'm Terry Gross, and this is FRESH AIR.

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GROSS: This is FRESH AIR. I'm Terry Gross back with physiologist Frances Ashcroft. Her new book is about how electricity powers the human body. It's called "The Spark of Life." In 1984, she made a scientific breakthrough involving what triggers the electrical impulse that controls the secretion of insulin in people who were born with diabetes. Ashcroft is a professor of physiology at Oxford University.

Something that you bring up in your writing is that people who are skeptical about like say, global warming or evolution, say with accusation it's just a theory and there's questions about it. But you point out like, all of science is theory.

ASHCROFT: Well, I think scientists are just like novelists in a way. We are all trying to tell a good story that explains how the world works. And we're interested in understanding how it works in exactly the same way that perhaps the early philosophers were, but we have much better tools with which to dissect it and understand it today.

And the thing about science is it's always based on the facts. So if the facts change and you discover new ones or many, many more new facts don't fit precisely with the old ones, then you have to change the story. So science is indeed a theory but I really like what the very famous American physicist Feynman said. He said science is imagination in a straitjacket. There are - we are constrained by all the things which we already know, so you cannot simply conjure a story out of the air, it has to explain all the current facts and the new ones which have just been discovered, and it has to make predictions that then can be tested to see whether in fact that story continues to hold where we know even more information.

GROSS: So another thing I want to ask you about his Botox. A lot of people get Botox treatments as a form of surgery-free cosmetic surgery.

(LAUGHTER)

GROSS: And Botox is botulinum. It's a poison from spiders, that's one of the most powerful naturally occurring toxins that we know of, and it paralyzes facial muscles so that the muscles that we use to wrinkle our brows can't wrinkle the brows anymore because they are paralyzed. So what's going on in terms of electricity, in terms of the kind of thing that you're writing about and researching with a Botox injection?

ASHCROFT: Oh, well, it's very interesting. What you're doing is you're paralyzing the muscle. And the way you are doing that is you're preventing the chemical signal that travels from the nerve to the muscle from leaping the gap. What happens when a nerve impulse fires off and runs down the nerve to tell a muscle to contract is when it gets to the end of the nerve cell it's got to somehow or another signal to the next cell in the chain - the muscle cell - that the muscle cell must twitch. But the electricity cannot jump the gap between the two cells.

And what happens is that the nerve releases - when the electrical impulse gets to the very end of the fiber, it releases a chemical signal, a chemical messenger that travels across the very tiny gap to the muscle fiber where it binds to receptors on the muscle cell membrane and then that opens more ion channels and triggers an electrical impulse in the muscle fiber that then causes it to contract. So what happens is that Botox blocks the transmission of those chemical signals so that the nerve isn't able to signal any longer to the muscle fiber, and so the muscle fiber is always relaxed. And that's how Botox works.

GROSS: So what's the downside of injecting minute amounts of this incredible toxin that's messing around between the communication of nerve and muscle?

ASHCROFT: So the downside, of course, is that you inject too much and then, of course, you get a frozen face. Your facial muscles are so frozen that you can't smile or laugh. But tiny amounts injected are fine because they're very localized and they don't move very far. But if you inject a little bit too much then you can paralyze the muscles that are involved in smiling or facial expressions. And that's a downside from having a Botox injection to your face.

GROSS: So where are you in research now? What are you working on?

ASHCROFT: Oh, well, we're doing a number of different things. One of the things we're doing is trying to actually see the particular ion channel that I work on, the particular protein. We want to do that at atomic resolution which means that we have to grow crystals of it - crystals like salt crystals - and put them in a huge synchrotron which shoots X-rays at it and allows us to see what it looks like.

Another thing we're trying to do is understand why some patients who have mutations in the particular protein I work on don't just have diabetes from birth, they also have neurological problems. They don't walk and talk at the right age, they're very delayed. That's what I'd really like to be able to understand, and also how we can help them.

And the third thing I'm interested in is trying to understand why people get fat. I think it's a hugely important problem and we're looking at a particular gene which goes by the wonderful name of the fat mass and obesity related protein, which is the gene that is the most common cause of obesity in the general population. And nobody understands how it works and so we're trying to figure it out.

GROSS: Thank you so much for talking with us. And for all of our sakes, I wish you really good luck with your research.

ASHCROFT: Thank you very much.

GROSS: Frances Ashcroft is the author of "The Spark of Life: Electricity in the Human Body." You can read an excerpt on our website, FRESH AIR.NPR.org.

Coming up, actress Amy Adams. She's starring in two new films, "The Master," and "Trouble with the Curve." This is FRESH AIR.

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TERRY GROSS, HOST: The new movie "The Master," written and directed by Paul Thomas Anderson, is getting a lot of attention for Anderson's masterful filmmaking and for the powerful performances by the film's stars, including my guest Amy Adams. She's also starring with Clint Eastwood and Justin Timberlake in "Trouble with the Curve." Her other films include, "Junebug," "Enchanted," "Doubt," "The Fighter," "Julie and Julia" and "The Muppets."

Let's start with a scene from "The Master," which takes place after World War II. Amy Adams plays Peggy Dodd, the wife of Lancaster Dodd, the charismatic leader of a cult called The Cause. Joaquin Phoenix plays a G.I. who is mentally unstable and unable to fit in anywhere or with anyone. Then he stumbles into a party of the cult members and tries to find a home with them. But Amy Adams' character becomes skeptical that he's right for the group and she's suspicious of his motives. Here she is sharing her concerns with her husband. He's played by Philip Seymour Hoffman.

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AMY ADAMS: (as Peggy Dodd) I wonder how he got here and what he's after. Is it really all so easy that he just came across us? He's a drunk and he's dangerous and he will be our undoing if we continue to have him here.

PHILIP SEYMOUR HOFFMAN: (as Lancaster Dodd) If we are not helping him then it is we who have failed him.

ADAMS: (as Peggy Dodd) Perhaps he's past help or insane.

GROSS: Amy Adams, welcome to FRESH AIR and congratulations on "The Master." At the center of "The Master" is a cult and your husband, Philip Seymour Hoffman is the founder of it. You're his, I don't know, like third or fourth wife, but like you're almost the power behind him. In some ways like you control him. What did Paul Thomas Anderson tell you about this cult that you and your husband lead so they could have enough of a backstory to fill in the details of it?

ADAMS: You know, it's interesting because in thinking about my conversations with him he didn't bring up any specificity as far as it being a cult or go study this religion or go read this. So for me, the way that I work, I didn't feel responsible for coming up with the history of this religion cult belief system. For me I always go into the character, so most of my discussions with Paul really had to do with my character, who she was, where she was from. She was very highly-educated and it was a time where women didn't have as many choices of what to do if they were very smart and very educated. It was just a different world.

And so I sort of came to the conclusion in doing my own research about that era that this was a woman who found her power behind a man really. And I thought it was a really wonderful opportunity to create somebody that I'd never played before, somebody who on the surface was very, very mothering, almost genteel and then underneath there was this boiling almost rage, this fierceness, and to play somebody with that kind of duplicity was very interesting to me.

GROSS: So you and Philip Seymour Hoffman's character put members of this group through different exercises, and one of them is questions - just like asking the same question over and over, like what is your name?

ADAMS: Yes.

GROSS: What is your name?

ADAMS: Yes.

GROSS: What is your name?

ADAMS: Yes.

GROSS: Do your past failures bother you? Do your past failures bother you? Do your past failures bother you? What did you think about or talk about when thinking about those exercises and why you're putting people through them?

ADAMS: Well, in the original script that I read my character was not involved in those. Paul very much would sort of come - he'd just say hey, come to set. I want you to do something. Like the in the film the exercise that I do is what color are my eyes? And he just had me look in camera and basically ask different questions as he called them out. It wasn't something that I had a lot of time to put a lot of thought into. He was telling me in the moment what to say, so it's a great exercise in staying focused and staying in character. It's almost like a hypnosis that I felt like I was hypnotized by the process of doing it, staring into camera and repeating these questions and that's what struck me when I was participating. There are a couple of times I appear on screen and those weren't scripted, those were in Paul's imaginings in the moment...

GROSS: That's really interesting because he's telling you what to do but on screen you're telling another character what to do.

ADAMS: Character what to do.

GROSS: Yeah.

ADAMS: Exactly. So who is the master?

GROSS: So it's like he's controlling you and your controlling Freddy. Yeah. Yeah.

ADAMS: Yes. Paul is the master and I'm happily a member of his cult.

GROSS: If you're just joining us, my guest is Amy Adams and she's one of the stars of the new Paul Thomas Anderson film "The Master." She's also currently in theaters starring with Justin Timberlake and Clint Eastwood in "Trouble with the Curve."

One of the ways you got your start with dinner theater. What's that like from the perspective as a performer, you know, when dinner is being eaten or served?

ADAMS: I took it very seriously. For me it was my Broadway, you know. I never knew where I would end up so for me it was all about living in the moment and I took it very seriously and I loved it. I loved the work. I loved getting, you know, to just sing and dance every night.

GROSS: What shows did you do?

ADAMS: I did "Brigadoon," "Anything Goes," "Seven Brides," a lot of shows.

GROSS: So you got to do a lot more classics than you ever would have done on Broadway.

ADAMS: Exactly. I probably never would have been hired on Broadway had I not moved out to LA and pursued acting and film, which is sad really. I just did Shakespeare in the Park.

GROSS: Yeah. I know, "Into the Woods," the Stephen Sondheim show.

ADAMS: Yeah and I worked with some amazing, amazing talent. And just working...

GROSS: "Into the Woods" is Stephen Sondheim's fairytale musical...

ADAMS: Yes.

GROSS: And there's like three different like parallel fairytales that are told.

ADAMS: Mm-hmm.

GROSS: And it's the really dark version of "Enchanted."

(LAUGHTER)

ADAMS: The second act is definitely. Yeah.

GROSS: Yeah. Because, you know, a few years ago you starred in the movie "Enchanted" as a princess living in - it's like an animated princess that starts off as animation...

ADAMS: Yeah.

GROSS: You meet your handsome prince and you're about to marry when the wicked queen intervenes and wants to get rid of you, so she pushes you down a well and somehow as you go deeper and deeper into the well, you emerge out of the well, but when you emerge you lift off this cap and it's actually a sewer cap in Manhattan.

ADAMS: Mm-hmm.

GROSS: And you climb out and you're not only in the middle of Times Square instead of fairytale land, you're also in the middle of like the real world as opposed to the animated world. Instead of an animated character, you are Amy Adams playing a princess.

ADAMS: Yes.

GROSS: And you have no idea where you are or what you're doing there. And then you get to sing in this too. And I thought I'd play little song in which you sing. And this is "Happy Working Song," and because you're tidying up this like single father's home who has taken you in because you have no place to go. You see that his apartment is really a mess so you lean out the window and sing and, of course, all the animals hear and want to come and help you.

Now in the animated movie it would be like, you know, the cute squirrel and the cute chipmunk and the cute bunny and, you know, all the adorable little forest creatures. But you're in Manhattan so, like, the roaches are coming out of the drain and the rats are, like, running out of the sewers and the pigeons are flying over and they're all coming to your house and they all help you clean. And it's hysterical and here is the song that - you're cleaning as all these, like, vermin are helping you tidy up the house.

ADAMS: Hello.

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ADAMS: Hello. Well, it's always nice to make new friends. All right, everyone, let's tidy things up. (Singing) Come, my little friends as we all sing a happy little working song, merry little voices clear and strong. Come and roll your sleeves up, so to speak, and pitch in, cleaning crud up in the kitchen as we sing along. Trill a cheery tune in the tub as we scrub a stubborn mildew stain, pluck a hairball from the shower drain to that gay refrain of a happy working song. We'll keep singing without fail. Otherwise, we'd spoil it. (Unintelligible) and scrubbing up the toilet. How we all enjoy letting loose with a little la da dum, dum, dum while we'll emptying the vacuum. It's such fun to hum.

GROSS: That's Amy Adams from "Enchanted." You really have a lovely voice. That's...

ADAMS: Thank you.

GROSS: That's so much fun. How old were you when you started in "Enchanted?"

ADAMS: I was 32, maybe. I was older.

GROSS: Yeah. It's, like, older for, like, the young princess...

ADAMS: Yeah.

GROSS: ...who, theoretically, would probably be, like, a teenager, so was it intentional to give the role to somebody your age?

ADAMS: I don't think so. Everyone sort of knew how old I was, so it didn't matter to them, as long as I looked and could play the part. I'm sure the DP had some challenges at times, but...

GROSS: So what did you do to get the kind of - those sweet, corny, like princessy gestures that you use in the film and when you're first in Times Square in Manhattan, you're in this, like, exaggeration of a princess gown with the puffy sleeves and the big, puffy skirt and it's such a gross exaggeration of it that it keeps getting in the way of everything.

ADAMS: Yes. I think it helped that I had been a dancer, so I tend to approach a character from a very physical place, anyhow. I went back and watched the older Disney films. "Snow White" had that a lot. She very much had that sort of hand push with the delicate fingers. And then, when I was working with the animators, they did a rough animation of how they saw Giselle running in the forest and I saw how they had her move and I thought, that's perfect.

And, really, they helped inform me and I just took it from there and kind of brought it into a three-dimensional world, but, really, I just used Disney animation from the past and then what they had come up with about how Giselle moved and one of the things that I loved is that she appeared to not understand gravity, like she didn't - she didn't understand weight, so when she moved, it was as though she didn't feel the floor and that was something I noticed about how she moved through the forest and I wanted to bring that as much as possible into New York.

GROSS: Is it ever like a relief to have lines written for you? Because, in life, you don't. In life, you have to really figure out what it is you want to say, knowing that what you might say might have consequences, but you know, when you're acting and you're reading lines, you can do that with abandon. It's not - you know, you don't have to think about - you have to think about how you're saying what you're saying, but you don't have to think about what words to use because those are taken care of.

ADAMS: Yeah. I'm much more comfortable speaking through my characters' voices than my own. I...

GROSS: Is that part of the reason why you became an actor?

ADAMS: I think so. I love talking and I love communicating with people and hearing new ideas, but I do get very self-conscious about how I form my thoughts and I tend to be somebody who acts from a very instinctual place and tries to live from a very instinctual place. So, on occasion, when I have to intellectualize an emotional experience, it's very hard for me.

So when I'm able to just get lost in the life of my character and in sort of emotional truth and reality that they experience, I really enjoy that and it helps me understand humanity a little bit more and that's one of the sad things about - once you become known as an actress, you can't disappear into humanity as easily and I've really missed that. I miss being a voyeur. I try. I just get caught now.

GROSS: Well, thank you so much for talking with us.

ADAMS: Thank you.

GROSS: You can see Amy Adams in two new movies "The Master" and "Trouble with the Curve." Coming up, film critic David Edelstein reviews the new time travel thriller, "Looper." This is FRESH AIR.

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TERRY GROSS, HOST: Writer and director Rian Johnson had an Indie hit with "Brick," a film noire parody set in a high school starring Joseph Gordon-Levitt. Now, the two have reteamed for "Looper," a futuristic time travel thriller in which Gordon-Levitt plays a hit man hunting his older self played by Bruce Willis. Film critic David Edelstein has this review.

DAVID EDELSTEIN, BYLINE: I adore time travel pictures like "Looper," no matter how idiotic, especially when they feature a love that transcends time. I love "Somewhere in Time" with Christopher Reeve and Jane Seymour. "The Time Traveler's Wife," even "The Lake House" with Keanu Reeves and Sandra Bullock in different years, sending letters through a magic mailbox. So terrible, so good.

See, everyone wants to correct mistakes in hindsight and it's the one thing we cannot do, except vicariously in movies. Oddly, though, it took me a while to warm up to "Looper," an unusually arty time travel thriller that evokes bits and pieces of "12 Monkeys," "The Terminator" and "Blade Runner," good models, but not when they're blended so haphazardly.

Yet there's something in "Looper" that gets to you. It's the year 2044. Cars can fly and the protagonist that narrator Joe played by Joseph Gordon-Levitt explains in one gob of exposition that time travel exists in the future, but is illegal. Yet, for some reason, organized crime finds it expedient to send people back to the past to be murdered by loopers like Joe. For some other reason, aged loopers in the future are now also being sent back to be killed by loopers, who'd seem, on reflection, the least reliable assassins, given their ties to the people they're supposed to shoot, including, on occasion, their older selves.

That's what happens to Joe. There he is, gun drawn, waiting for a looper to materialize. Poof, and it's him, old Joe played by Bruce Willis. No. The two Joes don't meld in your head. Bruce is always Bruce, but you go with it or you leave, so you go with it. Old Joe escapes which, in the peculiar logic of "Looper," means young Joe is in the toilet. So young Joe sends a message by carving a meeting place on his hand, leaving a scar on old Joe's hand, painful but very cool. They meet in a diner.

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JOSEPH GORDON-LEVITT: (as Joe) So do you know what's going to happen? You've done all this already as me.

BRUCE WILLIS: (as old Joe) I don't want to talk about time travel because, if we start talking about it, then we're going to be here all day talking about it, making diagrams with straws.

GORDON-LEVITT: (as Joe) We both know how this has to go down. I can't let you walk away from this diner alive. This is my life now. I earned it. You had yours already, so why don't you do what old men do and die?

WILLIS: (as old Joe) Why don't you just take your little gun out from between your legs and do it, boy?

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EDELSTEIN: If they talk about time travel, they're going to, quote, "be here all day making diagrams with straws." That's writer/director Rian Johnson giving himself a get out of jail free card, telling us, don't think so much. OK.

"Looper" has been acclaimed by some critics for stylishness and narrative invention, a testament to Johnson's greatest talent, making clumsy storytelling look tricky and sophisticated.

I haven't mentioned the MacGuffin. Old Joe is hunting someone in 2044 who'll grow up to be the Rain Maker, a future crime boss with supernatural powers who's killing all the loopers. That's when we get the telekinesis stuff, which feels like a different genre, like "Carrie" or "Firestarter."

Young Joe stumbles onto the farm of Emily Blunt, who points a shotgun at him in the wheat field and threatens to blow him in half. She has a strange little boy with pouty lips, a big head and temper tantrums that force her to tuck herself into a steel cabinet. The actors hold you through the loop-de-loops, Emily Blunt in particular, making emotional transitions that would trip up lesser actresses. Her face is incapable of registering a banal emotion.

As young Joe's boss, Jeff Daniels creates the year's most hateful bad guy by gazing on unfortunates with moist, sympathetic eyes before maiming them with a ball-peen hammer. Gordon-Levitt purges all traces of his puppy dog persona to play a cynic and drug addict who lives for today, not the future, until the notion of consequences hits him for the first time ever.

It's a big emotional payoff, happy and tragic in the right measure, and so "Looper," frustrating as it is, pulls safely into dock, leaving you to play out all the what-ifs and if-onlys as you mull it over with friends or lie in bed. That's the beauty of even semi-coherent time travel movies. You're making diagrams with straws long after the characters move on.

GROSS: David Edelstein is film critic for New York magazine. You can download podcasts of our show on our website, FreshAir.NPR.org, and you can follow us on Twitter at #NPRFreshAir and on Tumblr at NPRFreshAir.Tumblr.com.

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