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How researchers are trying to harness the electricity in the human body

Writer Sally Adee says scientists are looking into ways to manipulate the body's natural electrical fields to try and treat wounds, depression, paralysis, and cancer. Her new book is We Are Electric.

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Other segments from the episode on March 8, 2023

Fresh Air with Terry Gross, March 8, 2023: Interview with Sally Adee; Tribute to Wayne Shorter; Review of 'Return to Seoul.'

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TERRY GROSS, HOST:

This is FRESH AIR. I'm Terry Gross. One of the frontiers of medicine involves manipulating the naturally occurring electrical fields in our bodies. Each of the 40 trillion cells in your body is like its own little battery with its own little voltage, writes my guest, Sally Adee. Her new book, "We Are Electric," is about how medical and tech researchers are experimenting with possible ways to manipulate the body's electrical fields to treat or cure diseases and conditions, including depression, wounds, broken bones, cancer and paralysis. Probably the best-known already existing example of electric medicine is the pacemaker to keep the heart beating at an appropriate pace. Tiny, remote-controlled brain implants are being used to treat the symptoms of Parkinson's disease. Electric medicine can take the form of implants, wearable devices, shocks or electrical drugs. The key to the future of electric medicine is mapping the body's electrical signals so that we know what to fix when something goes wrong.

Sally Adee is a science and tech writer and the former features editor at the New Scientist. Sally Adee, welcome to FRESH AIR. This is really fascinating stuff. I learned so much about my body. So let's start with something personal. You participated in a military experiment. You tried it out. And the goal was to see whether sending an electrical current through a specific part of the brain would increase alertness and concentration. So basically, you were given what sounds like a video game where you had to, like, you know, shoot the enemy 'cause this is a military training exercise. So the goal was to see, you know, before and after - before the electrical current how you did and if your accuracy as a marksman, as a shooter was improved after this electrical current to sharpen your focus. So just describe the game a little bit.

SALLY ADEE: Sure. So this is called DARWARS Ambush. And I guess it was a training simulation so that you can learn, you know, marksmanship. They basically said that a little tiny bit of electrical current applied to electrodes on either side of your head - what it would do was decrease the time it would take to get from novice to expert by something like a factor of two. And so I really wanted to understand how it worked, but I couldn't talk to anybody who had undertaken these experiments. And so after a lot of cajoling, they let me fly over there to California in this sort of gray office park within which one room had been sort of kitted out with sandbags and, like, a close-range combat rifle, which was only firing CO2 rounds, but it was hooked into this simulation, which was, you know, like, a first-person shooter, like, basically designed to teach you accuracy in target shooting.

And so I started out - I was terrible, but they had me do all of these drills, and it was so discouraging. And I just kept thinking, I just want this to be over. And the whole time that they've got me doing these drills, I am connected to the device, which has a battery in the back of my bra basically, so that I can't see whether the device is on or not. And I've got the two electrodes, possibly active, possibly not. So I'm in there for, I think, what feels like hours. You know, it's this, like, video game kind of thing where people are coming at you, and you're supposed to protect the base. And I just keep getting blown up and blown up and blown up, and I just cannot get better at this. And I was just starting to panic a little bit. I've got a lot of, like, sort of angry self-recrimination, and I'm like, this is all a scam. And I just - I've got just, like, a lot of wasps in my head at this point.

And then he comes back in, and he fiddles with the device. And then the next round was a completely different experience. It feels like all the wasps have been herded out of the room. And all of a sudden this simulation or whatever that had been so complicated and overwhelming suddenly was incredibly straightforward. Like, I could just very easily tell who is the first, you know, sort of attacker that I need to pick off and who's the next one. And it was just so simple all of a sudden. And the tech comes in, and she's like, all right, you know, you're done. And I thought, well, you know, finally, I'm getting the hang of this. Can I just, like, go - and I was like, did I get them all? And she said, yeah. And I was like, well, where's the rest? And she said, no, it's over. And what had been 20 minutes felt like three minutes to me. And it was, like, a really profound experience that, you know, stayed with me until today.

GROSS: Wait, the experience stayed with you or the change in how your mind works changed - stayed with you?

ADEE: A little bit of column A, a little bit of column B, because the experience, like, the memory of it, was profound 'cause it wasn't just that experience. Like, then for the rest of the day, everything just got a little easier. Like, when I was driving back in LA traffic, basically - Southern California traffic - I'm usually quite a nervous, white-knuckling kind of a driver, and that was quite uncomplicated as well. I just kind of got on with it without all the self-recrimination and all the sort of ritualistic self-abuse that normally accompanies all - it's like the elevator music in my brain, and it was done. And then, you know, for the next three days, it was sort of, like, a gentle downslope from that. You know, I just sort of reintegrated into my life. But it stayed with me till today because suddenly it had offered me a new way of looking at my brainscape because I thought, well, hang on. Like, I didn't know that there are so many wasps in my brain. And then, yeah, just to this day I think that really changed things for me.

GROSS: So is the military actually using these devices now for training people?

ADEE: Do you know what? I have no idea, to be honest. I don't know - I'm not sure that they would because as I found out afterwards, the article that I wrote about this was more about electrical ways of inducing the flow state, which is this - you know, this is probably all over the place now. Flow is this state that you get into, this perfect state of mastery over, you know, whatever it is that you're doing, whether it's, you know, writing or carpentry or sharpshooting, people started saying, like, well, actually tDCS - transcranial direct current stimulation, which was the device that I'd been wearing - tDCS can't possibly work. You know, there was a big meta analysis out of Australia a couple of years later, and the researchers had said that we've, you know, looked at all of the different things that tDCS is supposed to help with - because in the meantime they had been researching it for, like, depression, anxiety, OCD, you know, focus, whatever - and they said when we average out all the studies, it doesn't do anything.

GROSS: So where do we stand now with it?

ADEE: And so I started to get really nervous. So OK, when you go back, the problem with a lot of the studies that had been done is that they were almost similar to what I did, where you have a really low number of people who are having tDCS. Like, and that's really important. That's an important step in science, is to have the studies that are done with a very small number of people. But they can't be the end result, right? That can't be the thing that you report, and you say, like, tDCS cures depression. What they've found afterwards is that tDCS is super hard to get right because you have to account for so many parameters. You have to account for things like whether that person drank coffee that morning. You have to account for the skull thickness. You have to account for all of the stuff.

And so the reason I'm telling you all this is because after this article came out and then all of these other sort of tDCS doesn't work, yes, it does, you know, sort of back-and-forth sniping, I was like, what the hell happened to me? I was like, did I fall for the placebo effect? Was I just completely wrong about all of this? And then people started talking about, like, these, you know, 100-year-old electro quackery devices. And I started looking at those, and I'm like, oh, crap. Like, you know, they've had this stuff. They had this stuff in the 1800s. There were like electrical penis belts and, like - sorry, like, just, you know - just a wild amount of, like, electro quackery when electricity was first discovered.

So I was really nervous that I had gotten it wrong. And the thing that was wild is that then I started asking people, like, look, how is this meant to work? And people just kept sort of repeating this sort of, well, nerves that fire together wire together. And I was like, but how does it work? And that's eventually how I found out about ion channels. And then I fell down, like, I don't know, like, a seven-year rabbit hole, and this book is the result.

GROSS: So I started off being, like, really, really excited about electric medicine, and now I'm discouraged because you told me that this maybe doesn't work, that the study that you were examining wasn't really big enough to give a really accurate appraisal of whether transcranial...

ADEE: Direct current stimulation.

GROSS: There you go - whether it really works or not. So anyways, there's really actually a lot of encouraging things happening in this field.

ADEE: Yeah. No. I mean, that's exactly...

GROSS: So let's lift our spirits and get to some of those. But let's start with a little bit of explanation first. It's hard for me to fathom that there's so much electricity running through my body that it can be manipulated for medical reasons. So you say every one of our 40 trillion cells is its own little battery with its own little voltage. What is the function of all this electricity? How does the brain use it to communicate to the rest of the body? And what other functions does the electricity serve?

ADEE: So the brain communicates with the rest of the body, and the rest of the body communicates with the brain via voltage spikes in neurons and muscle cells. So you basically - you have that tiny voltage in the cell. It's a signal. In fact, you know, a lot of neuroscientists refer to it as the neural code. Like - and they think, like, this, you know, sort of pattern of spiking underpins things like how memories are formed and, you know, how sensations are transmitted. And there have been a lot of really interesting implants that have shown that you can actually, for example, you know, make a person who perhaps has no sensation in their hand, for example - you can make them feel sensation in their hand by touching the proper sort of collection of neurons in that part of the brain electrically by sort of stimulating them electrically. And that's - you know, that's sort of settled science. So basically, that's the neural bioelectricity.

I mean, neuroscience is super important. But in a way, it's kind of overshadowed the non-neural component of bioelectricity, which - there's a researcher at Tufts University called Mike Levin, and he has looked into a lot of the bioelectricity of, like, development and regeneration and wound healing. And they think that the nervous system is one layer of communication in the body that's running atop a much deeper, older layer of communication in the body that is also bioelectric. And this is the stuff that's responsible for how you develop your shape in the womb, how you heal, like, whether your cells will go rogue and become cancerous. I mean, it's like - it's wild how much stuff there - how much research there is on this stuff.

GROSS: Well, I want to talk with you more about how electricity is being used in medicine. But first, we have to take a short break. If you're just joining us, my guest is science and tech writer Sally Adee, author of the new book "We Are Electric." We'll be right back. This is FRESH AIR.

(SOUNDBITE OF TODD SICKAFOOSE'S "TINY RESISTORS")

GROSS: This is FRESH AIR. Let's get back to my interview with science and tech writer Sally Adee, author of the new book "We Are Electric," about a new frontier in medicine, treating diseases by manipulating our bodies' naturally occurring electric signals.

Let's talk a little bit about cancer because I found this really fascinating. A lot of cancer research is focusing on genetics. What are the genetic precursors and genetic changes in cancerous cells, and how can we attack cancer by understanding more of the genetics? But there's an alternate way of looking at it, which is looking at the electrical system in the body. And you say when healthy cells turn cancerous, their electrical signaling changes radically. How does it change?

ADEE: Right. So this is research that was done by Mustafa Djamgoz at Imperial College in the - in London in the 1990s. He found that when you look at cancer cells under an oscilloscope, you can see that they begin to exhibit that spiking sort of voltage change pattern that I was talking about in neurons. They're doing that even though they have no business doing it. And what he thinks is going on is that these cells - there's a new ion channel that's been expressed, and it's causing them to start spiking in a communication type of way. And he thinks that that is part of how they decide whether to become invasive.

GROSS: So what is an ion channel?

ADEE: An ion channel is a pore in the cell membrane that decides which ion gets to come into the cell and which ion doesn't get to come into the cell. So you have different ion channels for different ions. So for example, sodium, which is a charged molecule - if it tries to get into your neuron, the ion channel - the potassium channels are like, no, no thanks. You're going to stay out there - almost like a little bouncer. They're just like, no. And what they do is they'll let the potassium ions in. And the whole reason that this matters is because when you have potassium inside the cell in a different concentration than it is outside the cell, your cell membrane acts, fundamentally, like a little battery. So your cell has a voltage. It has its own voltage. And those voltages are different in different kinds of cell. Nerve cells are different voltages than skin cells, bone cells, musculoskeletal tissue, liver cells.

GROSS: And that's where cancer comes in. The charge - the voltage or whatever of the cancer cells are different...

ADEE: Yeah.

GROSS: ...Than the - than...

ADEE: Yeah.

GROSS: ...Healthy cells.

ADEE: So once a healthy cell sort of abandons ship and decides that it's going to just be, like, a ravenous, invasive cancer cell, its voltage changes radically. And what you can do with an ion channel drug is change the electrical state of that cell by messing with the ion channels. And in tadpole experiments - and this is early days, but this is moving really fast. In tadpole experiments, they were able to use ion channel drugs to keep cells that had been genetically engineered to be tumors from changing their electrical voltage, right? And without doing any kind of genetic mucking around, they kept these tumors from forming in tadpoles that had been genetically engineered to express tumors.

And what's more exciting is that what they also were able to do is take cells that had already become cancerous, and just by dialing their electricity - their electrical profile - back to healthy electrical identity, they - it was like an undo switch. The cancer cells turned healthy again. And so this is early days. I have to say this. This is not something that they've done in people. But the bigger picture that's painted by all of this disparate research is showing us that electricity - bioelectricity can exert control over things like genetics. So it's like a powerful control switch.

GROSS: So tell us more about how this translates to treating cancer. Would they be using, like, channel blockers to block certain, you know, like, calcium or sodium from entering...

ADEE: Yeah.

GROSS: ...The cells?

ADEE: Well, so ion channel blocking drugs, it looks like it might be possible to block a certain particular kind of ion channel that forms on cells once they've become cancerous. So many scientists think that if you were able to, for example, keep a tumor that you have from metastasizing, you could keep cancer as a chronic disease and you could live with it for, like, 10 or 20 years. And, you know, metastasis is what kills people in cancer. So if you had a tumor that really wants to invade and eat and then you kneecap it's ion channels that are letting it actually express the behavior that's going to let it invade and eat and spread, then, yeah, that's a way to keep cancer chronic. And I think that's the first thing that we're going to see. And then this early tadpole work of being able to change the cell voltage so that the cells basically go into reverse from cancer to health, I think that's down the road a little bit.

GROSS: That sounds very exciting. So hopefully, scientists will figure out a way to harness what you're talking about and use it to treat cancer. So let's move on to something that is going to be something very few people know about, which is that there are experiments now about how electric medicine can be used to help heal wounds.

ADEE: Yes.

GROSS: So what is the principle behind that? Does wounded tissue emit a different electrical signal than healthy tissue?

ADEE: Yes. Yes, that's exactly right. When you cut yourself, the - all the ions in the skin, they just flow out. It's like a short circuit - you know, everything - it's called the wound current. And the wound current generates an electric field. And the thing about the electric field is that it attracts these cells from around the body, the macrophages, which are like the little, you know, mop-up janitor guys. It attracts, like, the repair cells. And all of these cells that are necessary to repair a wound and scar it over, those things, they all show up right dead center in the middle of your wound. And this electrical field, when you first cut yourself, it's quite big. It's like a loud signal. And as the wound heals over, this wound current gets less and less pronounced until when you are healed over, it's completely gone. There's no detecting it.

GROSS: So what are the implications for electric medicine in treating wounds?

ADEE: Well, if you could figure out how to amplify this wound current or manipulate it in some way, you could actually speed up wound healing in all kinds of wounds because all tissues have this, it's not just skin, you know, muscle and bone. If you could figure out how to speed it up. As - you know, some early research has found that it could be possible with electrical stimulation to speed up wound healing.

GROSS: If you're just joining us, my guest is science and tech writer Sally Adee, author of the new book, "We Are Electric." We'll be back after a short break. I'm Terry Gross, and this is FRESH AIR.

(SOUNDBITE OF BRAD MEHLDAU AND MARK GUILIANA'S "LUXE")

GROSS: This is FRESH AIR. I'm Terry Gross. Let's get back to my interview with science and tech writer Sally Adee, author of the new book "We Are Electric." It's about a new frontier in medicine, treating diseases and conditions with electricity. It's based on understanding the body's natural electricity and then manipulating it. We know that genetic irregularities can make us vulnerable to cancers and other disease. Electric medicine is based on understanding what's gone wrong with the body's electrical system.

Scientists are trying to understand systems, like mapping the genome so we understand more about genetics and how to target certain diseases when we're treating them. And then there's also the microbiome, which is understanding all the different good and bad organisms in our gut and how we can treat digestive problems by understanding those organisms and trying to maintain a healthy balance of them instead of an unhealthy system in the microbiome. Similarly, scientists working with electric medicine are trying to understand what's being called the electrome. What is the electrome, and why does that hold the key to electric medicine?

ADEE: So the electrome is a term that's been gradually bubbling up in bioelectricity research over the past, I think, seven years or so. And the electrome refers to all the electrical dimensions and properties of our cells and tissues and, you know, whole organisms. And what they're trying to get at is, how do all of these electrical dimensions link up with each other, you know, like the cells - how do they link up with, you know, the electrical properties of an entire tissue, like an entire organ, for example? But also, how do they connect with the other -omes (ph) that you were just talking about? You know, how does bioelectricity interface with genetics? How does it interface with everything else?

And, you know, we've known, and it's become increasingly clear over the past 100 years that all life is electric. So the question is, like, why is it electric? Like, what's it doing? And they're trying to study how electricity has power over other aspects of biology. And I guess the best place to start sort of talking about that is the way that bioelectric signals may control, you know, how we are shaped in the womb.

GROSS: So when we talk about how, you know, babies are formed in the womb to look like babies with, you know, eyes and nose and all that, we usually talk about stem cells, but this is a different way of looking at it. This is about looking at it through an electrical perspective. So what's the difference?

ADEE: So when a fertilized egg sort of, you know, differentiates into all the cells that it's going to become, the big question is, how does it know, you know, how to form itself into, like, a regulation-issue human that we can all recognize - two arms and two legs and eyes on the front, whatever? The particulars, like you said, like the eye color and the hair color and all that stuff - that's determined by genetics. But what about the general shape? How does it know that there's two eyes on the front and your feet face forward and your butt is behind you? There's nothing about that in the genome. Like, DNA doesn't have spatial information.

So there is growing evidence that there are bioelectric parameters that actually form a kind of blueprint that tells the body how to take shape. So they did this amazing experiment. Dany Adams - she was working on Mike Levin's lab at Tufts, and they injected tadpoles, developing tadpoles, with something called a voltage dye, which basically takes voltage and just converts it into something you can see with the naked eye like a brightness. And so she's watching these developing tadpoles. They don't have faces yet. They're just blobs.

At some point during development, all of a sudden there's this, like, shimmer, this electric shimmer, over the tadpole. And it's like a sort of ghostly pre-pattern of eyes and jaw and mouth. And then it goes away. And this is voltage, you know. This is voltage you're seeing. This is electrical.

And then a few hours later, exactly where that was, exactly the same shape of eyes and jaw and everything else starts to form. And you can see that these electrical signals - they were like a blueprint that was instructing the body where to put the face and how and what the shape is. And they think that this is actually instrumental for how all of our tissues form. You know, that's - I think that's the part that's really interesting, that, you know, the genes get turned on after, but somehow there's, like, something in the electrical signals that is instructing the body how to form itself.

GROSS: I don't know if this is part of the same experiment or not, but this fascinated me. There was an experiment in which, through some kind of electrical stimulation or interference, a frog grew eyes in various places on the body where eyes...

ADEE: Yes.

GROSS: ...Don't belong. Tell us about that.

ADEE: Yeah. So the next thing they did after they saw this ghostly pre-pattern, they were like, well, you know, what happens if we mess with just the ability for this frog embryo to have the electric pattern, right? So they used ion channel blockers to make sure that the frog embryo couldn't do those voltages. And after they did that, the frog embryos had terrible birth defects because these pre-patterns weren't just, like, you know, sort of random flashes. They were causative.

And after that they were like, well, wait a second, does that mean that we can actually precisely manipulate the body pattern? And that's where those experiments started. They manipulated parts of the tadpole to express the same kinds of voltages that would lead to an eye. They were able to grow eyes on a frog's gut. There was one where they grew an eye on a frog's butt, and it was light sensitive.

So, I mean, you know, who knows? Like, in the future, you know, you probably don't want an eye growing on your butt, but, like, what about - what if we grow eyes on the back of our head?

GROSS: Now, on a practical level, this applies to regeneration medicine. What is regeneration medicine?

ADEE: Absolutely. Well, regenerative medicine is sort of an umbrella term that brings in, you know, stem cells, prosthetics and, you know, all these things that are trying to replace what has been lost in the body. If like, for example, if, you know, you need a new liver or you've, you know, lost an arm, you know, this is all part of the same idea. And this is one of the most promising, I think, applications of bioelectricity because right now there's a lot of work trying to figure out how to get the body to regrow you something instead of going through all this trouble to try to create, you know, scaffolding of bone and then seed in stem cells and try to manipulate the genetics. Like, they think that maybe you can just sort of turn on the bioelectric code of development that I was just talking about with the whole, you know, patterning your shape thing. They think that maybe if you could just get the body to turn that back on again later in life, it could just grow you a new thing that you need, like, and you can just sort of not micromanage it, but let it do its own thing, let it kick-start that process by itself. Does that make sense?

GROSS: Well, it sounds remarkable.

ADEE: Yeah. Yeah, it does. It sounds science fiction, but, you know, Michael Levin at Tufts University - he likes to say, I think that at the end of the day, every problem that we have, whether it's healing wounds or cancer or development, it all comes down to the same basic question of how do you get a collection of, like, 40 trillion agents to do what you want them to do instead of what they want to do? That's what, I guess, unites this sort of bioelectricity research.

GROSS: Is there anything that you're most excited about right now, that you think has the most promise, based on what you've studied?

ADEE: So I think it's not any one particular thing, although I am excited about a lot of stuff, especially the stuff around wound healing. But I think it's more of like a sort of generalized excitement, right? So in the 19th century around now, like the 1820s or so, we had, like, two little tools. We had, like, a - you know, the first electrometer, and then we had, like, the sort of proto-battery. And we're starting to - and we were starting to, like, investigate, well, what is electricity really? How does it work? And, you know, we're just right at - we were just at the beginning of this question.

By the end of the 19th century, there were street lights lighting up London. We had the first telegraph wire that was connecting continents. We had the first power line. Electrolysis had put, like, 50 new elements on the periodic table. And now you sort of fast forward, and we're in 2023, and we've got these, like, amazing tools.

We've got, like, that voltage dye I was telling you about. We've got ion channel drugs. We've got, like, you know, optogenetics. We have all of these tools now, and they're advancing, you know. They keep spawning bigger insights, which then lead to, like, better tools, which then spawn better insights. And it's kind of snowballing.

So I just - like, I - you know, by the end of this century, like, will we be calling, like, the 21st century the bioelectric century? Like, I just think - I can't - you know, I want to live till the end of the 21st century so I could see this.

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

ADEE: Thank you so much for having me.

GROSS: Sally Adee is the author of the new book "We Are Electric." After we take a short break, jazz critic Kevin Whitehead will have an appreciation of Wayne Shorter, who died March 2. And John Powers will tell us why he's excited about the new film "Return To Seoul." This is FRESH AIR.

(SOUNDBITE OF CHARLIE HUNTER QUARTET'S "MIGHTY MIGHTY")
TERRY GROSS, HOST:

This is FRESH AIR.

(SOUNDBITE OF WAYNE SHORTER'S "HARRY'S LAST STAND")

GROSS: Jazz saxophonist and composer Wayne Shorter died on March 2 at age 89, more than 60 years since he began recording. Jazz critic Kevin Whitehead says Shorter was an inquisitive innovator inspired by film and literature as much as sounds - one of the great musical minds of our time. Kevin has an appreciation.

(SOUNDBITE OF WAYNE SHORTER'S "HARRY'S LAST STAND")

KEVIN WHITEHEAD, BYLINE: "Harry's Last Stand" from 1959. Wayne Shorter was always a double threat as composer and saxophonist. In either role, he liked pithy little phrases he could develop or maybe just repeat over and over, self-sufficient. But the harmony behind a hummable tune could be awesomely unconventional. Shorter might, say, layer one chord progression for horns over another for the bass. He wrote pieces with unusual structures that might trip up even top musicians. And yet the music had an easy elegance evident on albums he made for the Blue Note label in the 1960s. This is "Speak No Evil."

(SOUNDBITE OF WAYNE SHORTER'S "SPEAK NO EVIL")

WHITEHEAD: Wayne Shorter got an early break when drummer Art Blakey hired him to play and write for the Jazz Messengers. In 1964, Miles Davis drafted him into his brain trust with bassist Ron Carter, drummer Tony Williams and pianist Herbie Hancock, a Shorter ally ever after. Wayne wrote the quintet tunes that bounced around by the interval of a fourth, a rule-breaking move that became a marker of hip '60s jazz. The classic example is "E.S.P.," the opener and title track of Shorter's first album with Miles. Wayne even gets the first solo. He had arrived.

(SOUNDBITE OF MILES DAVIS' "ESP")

WHITEHEAD: Everyone in Miles' quintet started writing tunes like Wayne. His sinewy, economical tenor saxophone sound could be brusque or tender. Drawn into electric jazz a few years later, first by Miles and then as member of the jazz-rock arena band Weather Report, Shorter turned to the higher-pitched soprano sax, which could rise above the rumble. He adopted a thin, pointed, stabby tone, the better to pierce a thick texture.

(SOUNDBITE OF WEATHER REPORT'S "BLACK MARKET")

WHITEHEAD: Wayne Shorter kept busy with side projects during the Weather Report years, including reunions with the guys from Miles' old band and sessions with Joni Mitchell, Steely Dan and Carlos Santana. Shorter's album "Native Dancer" made an international star out of his featured guest, Brazilian singer Milton Nascimento.

(SOUNDBITE OF SONG, "MIRACLE OF THE FISHES")

MILTON NASCIMENTO: (Singing in Portuguese).

WHITEHEAD: Shorter could be used rather sparingly in groovy Weather Report. After they split up in the '80s, he made electric records that might sound like that band, but with more Wayne in it.

(SOUNDBITE OF WAYNE SHORTER'S "OVER SHADOW HILL WAY")

WHITEHEAD: Turning back to acoustic jazz, in 2001, Shorter assembled a quartet with pianist Danilo Perez, bassist John Patitucci and drummer Brian Blade, the saxophonist's main vehicle in the new century. The four only played together onstage, rarely rehearsing. But they all knew classic Shorter tunes they could slide in and out of and stretch every which way. It was a glorious return to form. This is from his golden oldie "Footprints," not that you'd recognize it.

(SOUNDBITE OF WAYNE SHORTER'S "FOOTPRINTS")

WHITEHEAD: Even in that late quartet, Wayne Shorter played more soprano than tenor sax. When he joined forces with classical musicians late in life, the little horn's spearhead sound made it easier to lead by example - sometimes, anyway.

(SOUNDBITE OF WAYNE SHORTER'S "PEGASUS")

WHITEHEAD: In 2021, Wayne Shorter premiered a chamber opera with improvisational elements, "...(Iphigenia)" - one more musical world to explore. The libretto was by Esperanza Spalding, one of a few women who recorded in Shorter's bands - among them, Terri Lyne Carrington, Geri Allen, Renee Rosnes, Patrice Rushen and Rachel Z. As composer and saxophonist, Wayne Shorter has been much imitated for decades by generations of musicians. He was a visionary. He influenced the course of jazz as much as anyone in the last 60 years.

(SOUNDBITE OF WAYNE SHORTER, CURTIS FULLER, JAMES SPAULDING, HERBIE HANCOCK, RON CARTER AND JOE CHAMBERS' "MIYAKO")

GROSS: Kevin Whitehead is the author of the book "Play The Way You Feel: The Essential Guide To Jazz Stories On Film." And he writes for Point of Departure and the Audio Beat. After we take a short break, John Powers will review the film "Return To Seoul," which he says surprised him from start to finish. This is FRESH AIR.

(SOUNDBITE OF MICHAEL BISIO QUARTET AND RON SODERSTROM'S "AM")

TERRY GROSS, HOST:

This is FRESH AIR. In the new movie "Return To Seoul," a young Korean woman, raised by adoptive parents in France, goes back to the country of her birth. The film was written and directed by Davy Chou and is now playing around the country. Our critic-at-large, John Powers, says that the story and lead actress took him to interesting places he never expected to go.

JOHN POWERS, BYLINE: In his great novel "If On A Winter's Night A Traveler," Italo Calvino makes a whimsical list of the many different kinds of books. One of them is called Books That You've Read Before They've Even Been Written - meaning they're so predictable that you know every beat in advance. This same genre thrives at the movies, where I often feel that I'm once again viewing a story I've been watching my whole life. That's why I was so excited by "Return To Seoul," a funny, melancholy, music-laced film that surprised me from start to finish. Written and directed by a Cambodian French director, Davy Chou, the movie starts off like a sentimental fish-out-of-water story about a young woman's search for her roots. But it quickly becomes clear that we're seeing something stranger and stronger. First time actress Park Ji-min stars as Frederique "Freddie" Benoit, who was sent off from Korea to France as a baby and raised by a white French couple.

Now 25, Freddy feels herself French. She doesn't speak any Korean. And a photo of her birth mom is all she has of Korea. But her life takes a strange turn when a typhoon changes her travel plans mid-trip and she winds up in Seoul. She's not exactly sure what she's going to do there besides wander around in her headphones, drink too much and hook up with cute strangers. She's not in search of her Korean origins, but many of the people she meets in Korea want her to be. It's as if they want her to behave like the heroine of a soppy immigrant drama about getting in touch with her family past. And because Freddie is aimless, she does wind up at the adoption agency that sent her and countless other Korean babies to the West. And this agency does put her in contact with her boozy birth father, a touching, absurd figure wonderfully played by Oh Kwang-rok, who wants her to move in with his family. Their first encounter, complete with weeping grandma and an aunt who erratically translates their conversation, is a triumph of droll awkwardness.

Although her dad dreams of reconciliation, Freddie is cussedly, almost seethingly, willful. She's a born refuser who bridles at people telling her what she ought to do. Early on, she's out drinking with two nice young Koreans who speak French. When she starts to pour herself a glass of soju, they stop her and say that in Korea, pouring your own drink is considered an insult to your companions. She registers the point, then promptly fills her glass with soju and swallows it down. The rest of the movie unfolds in similar fashion, with Freddie never quite doing what we or those around her expect.

With its shifting palette and attentive eye, Chou's style respects her unruliness. Rather than weave itself into a tidy narrative complete with tailor-made epiphanies, "Return To Seoul" lurches through eight years in a series of sharp, unpredictable episodes. Along the way, Freddie gets involved with a louche older Frenchman, takes a job selling weapons and half-heartedly seeks her birth mother. Freddie is clearly searching for an identity. Yet neither she nor the movie defines identity in terms of race, nationality or family - notions that Chou, himself a cultural outsider, thinks too broad to capture the multiplicity of lived experience. Although he has no ties to Korea, Chou does have imagination and empathy. And he clearly understands where Freddie is coming from. She's caught in a life of profound dislocation and is struggling to find herself, if it's even possible to pin down the self in such a way. Whether cutting her hair or getting involved with a new man, she keeps reinventing herself.

Such a story could easily be frustrating in its lack of closure. But I was held rapt by Park's bristling performance as Freddie, one made all the more astonishing because she's never acted before. Wow, does she have presence. Chou's camera carefully studies her features, which always contain something deep and wild and unknowable. The director Claire Denis, whose work this movie sometimes recalls, remarked that Park seems to resist being caught by Chou's camera. She's right. And Park's resistance gives the movie its singular, mysterious edge. In fact, her work here is more fascinating than any of this year's Oscar nominees for acting. Jean Luc-Godard is famous for saying that all it takes for a movie is a girl and a gun. Carried aloft by its star, "Return To Seoul" proves that sometimes you don't even need the gun.

GROSS: John Powers reviewed the new film "Return To Seoul." Tomorrow on FRESH AIR, my guest will be writer Thomas Mallon. We'll talk about excerpts of his diaries that were recently published in The New Yorker in a piece titled "Finding My Way - And Staying Alive - During The AIDS Crisis: A Diary Of Nineteen-Eighties Manhattan." Mallon was in his 30s then. His latest novel is based on the life and murder of Dick Kallman, a closeted actor in the 1950s and '60s. I hope you'll join us.

(SOUNDBITE OF DOMINIC MILLER'S "CHAOS THEORY")

GROSS: Our interviews and reviews are produced and edited by Amy Salit, Phyllis Myers, Sam Briger, Lauren Krenzel, Therese Madden, Ann Marie Baldonado, Thea Chaloner, Seth Kelley, Susan Nyakundi and Joel Wolfram. Our digital media producer is Molly Seavy-Nesper. I'm Terry Gross.

(SOUNDBITE OF DOMINIC MILLER'S "CHAOS THEORY")

Transcripts are created on a rush deadline, and accuracy and availability may vary. This text may not be in its final form and may be updated or revised in the future. Please be aware that the authoritative record of Fresh Air interviews and reviews are the audio recordings of each segment.

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