Memory Hackers

PBS Airdate: February 10, 2016

NARRATOR: Memory: it's the key to our identity.

JOE LEDOUX (New York University): Without memory, we're nothing.

DANIELA SCHILLER (Icahn School of Medicine at Mount Sinai): It's who we are.

NARRATOR: But how does it actually work?

JULIA SHAW (London South Bank University): It's a huge mystery.

NARRATOR: Today, scientists are probing our brains like never before,…

ERIC KANDEL (Columbia University): We're seeing a memory being formed in front of your eyes.

NARRATOR: …and finding clues that lead us to shocking new places.

DANIELA SCHILLER: You know, your memory is not as accurate as you think it is.

STEVE RAMIREZ (Massachusetts Institute of Technology): We can tinker with a specific memory, at will.

MATT WALKER (University of California, Berkeley): Perhaps Mother Nature needs a little bit of tweaking on the dials.

NARRATOR: From editing memories,…

CHRISTINE DENNY (Columbia University): We can implant a false memory.

NARRATOR: …to deleting our worst fears,…

SASHA COHEN (Memory Reconsolidation Study Subject): It was unbelievable. And I was just standing there, like, how could it be possible? I used to be terrified of spiders.

MEREL KINDT (University of Amsterdam): We target and even erase the fear memory, itself.

NARRATOR: Are we approaching a day where, at the flick of a switch, we can rewrite our past?

ANDRÉ FENTON (New York University): Being able to use new technologies to edit memories is frightening.

STEVE RAMIREZ: I think that it's a matter of when this happens, not a matter of if it'll happen.

NARRATOR: Memory Hackers, right now, on NOVA.

MAN #1: I remember….

WOMAN #1: I remember….

MAN #2: I remember….

MAN #3: I remember….

MAN #4: Hmm..

NARRATOR: Memory: we know it as a record of our lives: how to find our keys or recite facts from school. But stop and think about it for a moment. It's so much more. From your earliest memory…

MAN #2: …falling off a horse, when I was 5 years old.

WOMAN #2: …when I walked into kindergarten, and I met my best friend.

MAN #5: About 1925, we moved to 513 Spring Avenue.

NARRATOR: …your happiest…

MAN #6: …when my daughter was born; when she came out.

MAN #7: Seeing a real life human being breathing that first breath of fresh air.

NARRATOR: …or saddest…

WOMAN #3: …the death of my father.

NARRATOR: …we are little but the sum of our memories.

DANIELA SCHILLER: It's who we are. That's how we understand ourselves and our lives.

NARRATOR: Consider, for a moment, just how vivid a memory can be:

MAN #7: … the smells, the sounds

MAN #8: …the shoes, the socks, the pants I wore.

WOMAN #4: It was like it happened yesterday.

MAN #9: I do have a picture in my head.

MAN #5: I can see it!

MATT WALKER: That is a remarkably complex computational process, that my memory achieved within milliseconds; what an incredible, powerful gift.

NARRATOR: How is this gift possible? How does the world get into our heads and turn into a memory? How does memory actually work?

Turns out, that's one of the biggest mysteries in science today.

ANDRÉ FENTON: If you go and ask most people, they would say they understand memory, but they truth is really, rather far from that. We sort of understand the tip of the iceberg.

RODDY ROEDIGER (Washington University in St. Louis): We're, kind of, nibbling around the big central mystery of memory: how do I bring back in time, now, something that happened to me long ago? It's a very difficult problem that we haven't solved.

DANIELA SCHILLER: Memory is, the biggest mystery. It's as big as, "What is the universe? Why are we here?"

NARRATOR: Could this 11-year-old boy hold one of the keys to unlocking the mystery?

On first glance, Jake Hausler looks like a normal fifth grader, but as Washington University's Roddy Roediger is discovering, he seems to be anything but.

RODDY ROEDIGER: What happened Friday, October 28th, 2011?

JAKE HAUSLER (Memory Study Participant): World Series game seven; Cardinals won, six to two.

RODDY ROEDIGER: Who were the pitchers for the teams?

JAKE HAUSLER: Chris Carpenter for St. Louis, Matt Harrison for the Rangers.

RODDY ROEDIGER: We're just getting to know Jake and just starting to study him. He's obviously a bright kid with a different kind of very powerful memory.

Let's try a different day here. How about May 4th, 2013?

JAKE HAUSLER: That was a Saturday, and I saw Iron Man 3.

KATHLEEN MCDERMOTT (Washington University in St. Louis): He appears to have a pretty unique ability. So, he can tell you what he did years ago to this date. And that's very, very unusual, in and of itself. And to find it in a child is particularly unusual.

RODDY ROEDIGER: When was Osama bin Laden killed?

JAKE HAUSLER: May 2nd, 2011, in Pakistan; May 1st, 2011, in the U.S.A.

RODDY ROEDIGER: I mean it's amazing. I've never felt like my memory was particularly bad, but compared to Jake's, clearly, it is. It's just a mystery as to what's going on here.

NARRATOR: Jake can remember details from almost every day of his life since age seven.

SARI HAUSLER (Jake Hausler's Mother): Once he started speaking, really, we noticed he was different.

What were the 13 colonies?

JAKE HAUSLER: Georgia, Connecticut, Massachusetts, Maryland,…

ERIC HAUSLER (Jake Fausler's Father): I remember taking him to the grocery store one time, and he knew where all the items were by aisle.

It's a little bit like having a computer living with you.

NARRATOR: We'd all remember getting a pet, but the exact date?

ERIC HAUSLER: What day did I pick up Gracie, in Wisconsin?

JAKE HAUSLER: March 31st.

ERIC HAUSLER: What airport did I fly into?

JAKE HAUSLER: Minneapolis-St. Paul.

ERIC HAUSLER: What did I have for dinner?

JAKE HAUSLER: Cheese curds?

ERIC HAUSLER: That is correct.

Yeah, there's no doubt that there's something different going on there.

NARRATOR: What's different about Jake is that he has H.S.A.M., highly superior autobiographical memory.

JAKE HAUSLER: Highly superior, you can remember days from your life and lots of detail, like what day of the week was it, and you can't forget.

NARRATOR: Jim McGaugh is one of the pioneers in the science of memory. He discovered H.S.A.M. 15 years ago.

JIM MCGAUGH (University of California, Irvine): When did you meet with me?

BOB PETRELLA (Memory Study Participant): June 28th, 2008.

NARRATOR: So far, out of the several thousand candidates tested, he's discovered 55 adults who have this amazing ability.

BOB PETRELLA: A Saturday, at Panera Bread, at Newport Beach.

JIM MCGAUGH: I can give them any date, say 10 years ago, five years ago, 20 years ago and so on.

Do you know when Elvis Presley died?

BOB PETRELLA: August 16th, '77.

JIM MCGAUGH: Their performance will be at least 80 percent correct, and maybe 100 percent correct, depending upon the particular individual.

NARRATOR: One of the best memories McGaugh has ever tested belongs to someone you might recognize: actress Marilu Henner, from the hit show Taxi.

MARILU HENNER (Memory Study Participant): I knew, as a very young child, I had a very good memory. You know, they called me "Ms. Memory," "Ms. Univac," the "Memory Kid," things like that.

NARRATOR: Name-calling aside, they're not geniuses. In fact, on average, they have normal I.Q.s.

JIM MCGAUGH: They are not superior in other forms of learning, like book learning, standard laboratory learning tasks and so on.

BOB PETRELLA: I think a misconception, as I think you probably know, that people have is that they think it's some kind of autistic savant thing, that we're using some type of mathematical calculation, like in Rain Man—yeah, definitely not Rain Man.

NARRATOR: So what gives them this amazing ability?

McGaugh has scanned over a dozen H.S.A.M.s, and found some intriguing hints. For example, an area in the brain associated with memory, the uncinate fasciculus, is more active in H.S.A.M.s.

JIM MCGAUGH: There are some differences in the brains. They're statistically significant. But they have not given us a pattern such that we can say, "This is the neurobiological basis of H.S.A.M." What is it about their brains that enables this ability? That's the open question.

NARRATOR: And that's where Jake comes in. He is the youngest person ever discovered with H.S.A.M., and here, at Washington University, scientists are mapping his brain. Over the next year, they'll test his memory while doing hundreds of scans.

ADAM EGGEBRECHT (Washington University): All right, Jake, what happened on April 8th, 2013?

JAKE HAUSLER: I went to the St. Louis Zoo.

NARRATOR: When they are finished, they will have perhaps the most comprehensive picture ever of a child's brain.

KATHLEEN MCDERMOTT: We're getting loads and loads of data on him. It's very, very exciting. And to do this in a normal person, in this comprehensive a way, would be very, very exciting, but to be able to do it on a child that has particularly unique abilities is extra special.

NARRATOR: Then they will compare Jake's scans to other children's to see if they can unlock the secret of what makes his memory so extraordinary.

NICO DOSENBACH (Washington University in St. Louis): It's a chance of a lifetime. You, you know, you actually, I don't think…You can't write a grant saying we're going to go look for someone like him, 'cause it's…you'll never find him, right?

NARRATOR: The hope is that this little boy's brain can help answer some big questions about how our memory works.

ADAM EGGEBRECHT: Jake clearly is able to extract remarkable amounts of information from his brain. But we don't know if you or I have that information in us, but we just can't remember it, or if it just doesn't get encoded into our brain function, in the first place.

NARRATOR: The mystery with Jake and the other H.S.A.M.s is: do they actually keep more memories than the rest of us, or do we all have this wealth of detail buried deep inside our brains; we just can't get at it?

ADAM EGGEBRECHT: If we could understand how he harnesses that, to be able to generate within ourselves could be a very powerful tool.

JIM MCGAUGH: There is potential there that we will learn something truly new and important about the functioning of the most complicated and interesting known structure in the universe, and that's our brain. And the most important thing it does is learn and remember.

NARRATOR: But what exactly is a memory? Amazingly, this simple question has stumped thinkers for ages. Until the 1950s, few clues emerged, and then came a single patient who would change everything.

JIM MCGAUGH: Well, when I was a young researcher, learning was learning and memory was memory, and it was just, you know a thing that happens. And then along came the findings of Brenda Milner and H.M.

NARRATOR: H.M. stands for Henry Molaison, Patient Zero in the study of memory. After a childhood bicycle accident, Molaison began to suffer severe epileptic seizures.

MATT WALKER: To try and quell those seizures, neurosurgeons performed an operation where they removed the parts of his brain that they thought were creating those seizures.

NARRATOR: Much of what they removed came from a part of the brain called the hippocampus. After the surgery, his seizures were gone, but there was an alarming side effect.

MATT WALKER: From that point forward, he could no longer make any new memories. He was what we call "densely amnesiac."

NARRATOR: It could only mean one thing: the hippocampus must be the part of the brain responsible for creating new long-term memories. This in itself was a breakthrough, but that was just the start.

BRENDA MILNER (Recording): Do you know what you did yesterday?

HENRY MOLAISON (Recording): No, I don't.

BRENDA MILNER (Recording): How about this morning?

HENRY MOLAISON (Recording): No.

NARRATOR: Brenda Milner wanted to know, despite his amnesia, could he still have some form of memory?

BRENDA MILNER (McGill University): He was a very nice person. He was very cooperative. He, fortunately for us, he liked doing tests, he liked puzzles.

NARRATOR: So, she came up with a puzzle for H.M., to trace a star shape, using only a mirror to see his hand.

BRENDA MILNER: If you try this, it's jolly difficult, but, but normal subjects, with practice, a few trials, learn to do this thing,

NARRATOR: Because H.M. appeared to have zero ability to make new long-term memories, he should be hopeless. He shouldn't be able to learn anything.

BRENDA MILNER: How's he going to do? I didn't know. I didn't know. I had no idea.

NARRATOR: And, in fact, every time Milner asked him to train, he claimed he'd never done the task before. But his performance betrayed him: he got better and better until…

BRENDA MILNER: I was so excited, because this is a breakthrough. He can't remember the events of his life, but he can learn motor skills.

NARRATOR: The fact that H.M. could remember motor skills, but not new events in his life, meant that memory couldn't be just one thing.

DAN SCHACTER (Harvard University): We had to leave behind the notion that there was just one kind of memory. We now knew that there are different kinds of memory and those different kinds of memories depend on different parts of the brain.

NARRATOR: Knowing where memories are in the brain is one thing, but how do they get there? How does a long-term memory get written in the brain in the first place?

These are the questions that have driven Nobel Prize winner Eric Kandel for over 60 years. It all started back in Vienna, on his ninth birthday.

ERIC KANDEL: I received a marvelous little toy car that I drove with great pleasure through our small apartment.

NARRATOR: Two days later was Kristallnacht, the infamous "Night of Broken Glass." In that violent prelude to the Holocaust, thousands of Nazi soldiers stormed the Jewish neighborhoods in Vienna.

ERIC KANDEL: On November 9th, there was a knock on the door and two Nazi policemen came in and said, "Pack all your things." When we came back a week later, everything of value was gone, including my little toy car. That was a very painful experience.

NARRATOR: A painful experience that would define his life's work.

ERIC KANDEL: Everyone who went through the Holocaust…there are memories that you can never forget.

NARRATOR: Kandel wanted to know: how did that experience become a memory he would carry with him for life?

ERIC KANDEL: That got me interested in psychology and psychoanalysis. And when I got interested in that, I said, what's the central question in psychoanalysis? It's memory, how we recall things.

NARRATOR: But where to start? His biggest lead was Milner's early work with H.M.: the hippocampus is crucial for forming new memories. But how do they get there? Could there be a physical mechanism on the cellular level?

ERIC KANDEL: So, I thought I would record from single cells in the hippocampus, and those cells would be so unique, they would speak to me about memory storage.

NARRATOR: Within months, he was able to record the sound of hippocampal neurons firing.

ERIC KANDEL: Our colleagues were euphoric, but we didn't learn a darn thing about learning and memory. So, I realized one needed to take a reductionist approach. And I thought I would use a simple animal, with a simple nervous system, simple behavior, and try to study that.

NARRATOR: Enter Aplysia californica, a giant sea slug, with one of the simplest nervous systems in the animal kingdom.

ERIC KANDEL: One of the great giants in the field thought I was throwing my career away. In my naiveté, I was confident that this would be right.

NARRATOR: He thought if he could just isolate the cellular changes that occurred when Apylsia learns simple tasks, it would be the key to understanding our memory.

KELSEY MARTIN (University of California, Los Angeles): Humans have neurons, sea slugs have neurons. They're not that different, right? Even the at the level of D.N.A., our D.N.A.'s not so terribly different. The same fundamental kinds of changes should underlie memory.

NARRATOR: To test his hypothesis, Kandel's first step was to create a memory in the sea slug. To do that, he trained it to fear a light touch.

ERIC KANDEL: If you touch it in the siphon, it'll withdraw the siphon.

NARRATOR: The siphon is the slug's water spout. When it is touched, it also withdraws its gill slightly, as a protective reflex. But pair that touch with a mild shock, you get a much stronger reaction. And do it repeatedly. Now, when you touch the animal's siphon again, even weeks later, without a shock, it reacts as if it got shocked. Somehow it remembers that that light touch means shock. It has formed a long-lasting memory.

The question is how?

Kandel had a hunch. If he could just replicate that touch experiment with single cells, he could see exactly what was going on to make a memory.

ERIC KANDEL: We could take the cells out of the animal, and put it into cell culture, and reconstruct the neural circuit. We could look at each level and see what happens with, with long-term memory.

KELSEY MARTIN: It was this huge breakthrough. What Eric Kandel really did was he took this phenomenon of memory and turned it into a biological question: what are the changes that are happening that give rise to memory?

NARRATOR: To find out, Kandel's team extracted two neurons from the sea slug. This is a sensory neuron from its siphon, and that's a motor neuron from the tail. They are connected by a single synapse.

ERIC KANDEL: The synapse is the point of contact, is where one neuron talks to another.

NARRATOR: Then, to simulate a long-term memory, just like with the live animal, Kandel repeatedly stimulated the sensory neuron. And when he did, suddenly, something magical happened. New synaptic connections started to grow.

ERIC KANDEL: This made us realize, for the first time, that long-term memory actually involves an anatomical change in the brain, whereby new connections are being formed. And that just really blew us away the first time we saw it.

JOE LEDOUX: That was a phenomenal discovery, because it showed us, for the first time, that memory involves a structural physical change in the brain. That became the foundation for our whole conceptual basis for understanding memory.

NARRATOR: Using today's technology, you can witness this process first-hand.

ERIC KANDEL: This shows you the nucleus in the cell.

NARRATOR: After repeated stimulation, the neuron's nucleus starts to pump out these tiny glowing specks called m.R.N.A., recipes for building proteins. They're about to travel down to the synapse, with instructions to build new connections.

ERIC KANDEL: And you see this magnificent voyage that this particle, which is carrying this m.R.N.A., to the synapses.

NARRATOR: When it gets there, the instructions are released, and the new connections grow, seen here in green.

ERIC KANDEL: We're seeing a memory being formed in front of your eyes. These anatomic changes occur in your brain, when you learn and remember something.

NARRATOR: From sea slugs to humans, these physical changes are considered the biological basis of memory.

RODDY ROEDIGER: It's an article of faith, at this point, that the mechanisms that he's uncovered are fundamental ones to learning and memory for all of us.

NARRATOR: Kandel's work launched new way of probing memory, one grounded in biology and built around a simple premise: the growth of new connections is what allows a memory to persist for days, months, even years.

But that was just a piece of the picture, a basic mechanism for how memory works at the level of single cells. Even in a sea slug, a real life memory is made of about 50 neurons out of 20,000. In a human, it's more like tens of thousands out of 100-billion. Somehow, it's this network that stores a memory, which begs the question, where, exactly, does a particular memory live in us? To this day, that remains a mystery, but we aren't without clues.

In the last 25 years, new imaging tools have allowed a generation of explorers to chart memory in the human brain. And today, we can finally begin to draw a rough map of where some of our most treasured memories live. For example:

ANDRÉ FENTON: Take something like your first kiss. Most people remember their first kiss.

WOMAN #1: Do I remember my first kiss?

ERIC KANDEL: Hahaha.

DANIELA SCHILLER: Yeah, I do.

WOMAN #2: I do, hahaha.

MAN #1: When did I kiss that girl? My wife?

DANIELA SCHILLER: There was an Italian, this dashing Italian.

NICO DOSENBACH: She was like, "This is something that people do that like each other." And I was, "Okay, I like you."

ANDRÉ FENTON: I remember planning this kiss for about a week.

MAN #2: Her friend whispered to me, "Make a move," and walked faster. And, all of the sudden, Laura and I were alone in, kind of, a grove of trees.

WOMAN #3: He takes my face, like this, and plants one on me.

ANDRÉ FENTON: It was like the universe exploded or something like that. It felt like, suddenly, everything was different.

MATT WALKER: The question is, where is the memory? And what we have come to understand, there isn't a nicely packed memory that's, sort of, folded up like a letter and placed inside of an envelope, in one specific area of the brain. Different parts of memory are coded in different locations in the brain. Think about your first kiss. The visual elements are coded at the back of the brain, in the visual cortex; the smell components are coded in the olfactory cortex, just above the nose; and you can also remember the postural positions, the motor positions, the motoric, the kinesetic, elements are coded up here, in the motor cortex; the emotional elements are coded in deep-brain structures like the amygdala. And, together, it is the hippocampus that is going to grab ahold of those brain anatomical areas, those balloons of information, and it is going to bind them together and produce a memory that you are capable of remembering.

NARRATOR: So, if different parts of a memory live in different parts of the brain, and we know that the growth of new connections between neurons is important for storing them, that would suggest that every memory is physically tattooed onto our brains. So, how come we don't remember them all?

KELSEY MARTIN: So the question is, if there are these structural changes that give rise to memory, but memories are changeable and dynamic, how can that be?

NARRATOR: Perhaps the answer can be found in the act of remembering itself.

Think about it for a moment. A memory only comes alive when you recall it. What happens in your brain each time you recollect a past experience?

That's what Karim Nader wondered. His quest for answers started when he was a grad student at one of Kandel's lectures.

KARIM NADER (McGill University): Eric Kandel came and gave this brilliant talk. He had beautiful pictures, showing synapses could grow over time. The work is very elegant. It took everyone's breath away.

NARRATOR: Looking at those pictures gave Nader an idea.

KARIM NADER: Why would all of this happen just once? Wouldn't it be cool if it all happened again when you recalled the memory?

NARRATOR: If Kandel's work helped establish that memories can't form without new proteins that build new connections, what happens to those connections when you remember something?

At the time, memory was pictured kind of like a library.

STEVE RAMIREZ: The underlying dogma was that, when you formed a memory, it was filed away in your brain, and that's it.

NARRATOR: It's called consolidation.

STEVE RAMIREZ: You can't modify it, it just is. It's just in the brain.

NARRATOR: So when you remember your first kiss, you pull out that book, look at it, and put it back. Though it may fade over time or get lost in the stacks, the original story, or memory, is always still there.

Nader wondered, could this really be true? Is it possible that just the act of recalling the memory could rewrite the story? To find out, Nader designed an experiment.

JOE LEDOUX: When Karim told me he wanted to do that experiment, I probably said something like, "Don't do it. Don't waste your time." Being a smart guy, he went off and did it.

NARRATOR: So, Nader decided to put his idea to the test.

He started by training rats to fear the sound of a tone, by pairing it with a mild shock.

KARIM NADER: So, right now, he's really scared. He doesn't like this at all.

NARRATOR: Just like Kandel's sea slugs, the rats quickly learn to fear the tone alone. They have formed a long-term memory that the tone predicts shock. So, every time it hears the tone…

KARIM NADER: So you see, even though there's no shock, the animal's freezing. It's afraid.

NARRATOR: We know the rats' brains have built new connections to store the memory. But what happens to those connections when the rat recalls the memory? To find out, Nader first plays the tone to remind the rat of his fear, and when he freezes,…

KARIM NADER: The next part is giving him a compound directly.

NARRATOR: The compound is anisomycin, a drug known to block the proteins needed to build the connections that store new memories. But Nader's rats have already formed the memory; they're just recalling it.

If memory consolidation really is like a book in a library, the drug should have no effect. The rats' brains should have built a permanent memory, and they should still freeze when they hear the tone.

KARIM NADER: So, if the memory is wired in the brain, this drug should have absolutely no effect.

NARRATOR: But now when Nader plays the tone…

KARIM NADER: Oh, my god.

NARRATOR: …he keeps moving,…

KARIM NADER: You would think the animal should be freezing, if it still had the memory there, but now it is acting as if the memory has been erased from its mind.

NARRATOR: …as if it never learned to fear the tone in the first place. The memory appears to be gone.

KARIM NADER: My jaw just dropped. I couldn't believe it. So I ran into my supervisor's office going "[Expletive] I can't [expletive] believe this happened." I mean, the probability of this happening is like zero, right?

NARRATOR: Because a drug known to block the formation of new memories also blocked them during recall, it means the act of remembering must make the memories vulnerable to change.

In other words…

KELSEY MARTIN: It's not this, "you have a memory, you encode it and it's stuck there." But instead, what it means is that every time that memory is recalled, it is vulnerable to alteration.

ERIC KANDEL: Nader's discovery that any time you recall a memory you essentially disrupt it was a significant advance.

DANIELA SCHILLER: It changes everything we think about memory.

STEVE RAMIREZ: It turns out, memory is not at all, actually, like putting a book away in the library of the brain, but it's more like bringing up a file on your computer and constantly modifying that file.

NARRATOR: The theory is every time you recall something, you have pull it up off the hard drive to view it. For it to return to long-term memory, you have to hit "save" and reconsolidate the memory, by creating new proteins to essentially rewire the memory into your brain.

DANIELA SCHILLER: Imagine something precious in a box. And then each time you take it out, it changes a little bit. And then you put it back. Then take it out, changes a little bit. That's how your memory works.

NARRATOR: The idea that the simple act of remembering could make your memories vulnerable to change transformed our understanding of memory. Within a few years, Nader's findings were replicated in dozens of species and led to over a thousand experiments, and even, reportedly, inspired the movie Eternal Sunshine of the Spotless Mind.

But what if this isn't just the stuff of movies? What if it's possible to use reconsolidation in humans? Perhaps to erase certain memories in all of us, like the ones that keep you up at night.

MAN #1: Heights, I'm terrified of heights.

WOMAN #1: I don't want to be on a ladder. I don't want to be looking down.

WOMAN #2: I can't tell you the last time I've been in a pool, the last time I owned a bathing suit. But, I mean the water gets, probably right here, and it's like "huu huu uhh uhh."

SARI HAUSLER: Elevators.

MAN #2: Snakes are the worst.

MAN #3: I don't know what it is about bees, but I can't be around them.

WOMAN #3: Spiders; I'm petrified of spiders, even the smallest ones.

SASHA COHEN: Terrified; if I see a spider, I don't want to come near it. I'm really scared of spiders, or, at least, I used to be. But now, I am just completely relaxed, sitting here with a tarantula. It is really crazy.

NARRATOR: Ever since she was a little girl, Sasha de Waal has been plagued by her fear of spiders. But thanks to a new therapy, using reconsolidation, that fear seems to have been erased.

SASHA COHEN: I am petting a poisonous spider, indeed.

NARRATOR: The scientist who cured Sasha is Professor Merel Kindt, at the University of Amsterdam. When she heard about Karim Nader's work, she immediately saw the potential.

MEREL KINDT: I was really thrilled. I realized that, if this is going to work for humans, this is very important news.

Okay, tell me a bit more about your fear of spiders.

NARRATOR: Using reconsolidation, she has a developed a treatment to erase patients' lifelong fears.

MEREL KINDT'S PATIENT: As long as I can remember, I am afraid of them. They just scare me.

MEREL KINDT: Just fear.

MEREL KINDT'S PATIENT: When I sleep, I dream about it. I am very scared. I just dream about it.

MEREL KINDT: For the treatment, we will walk to the other side of the room, and there is terrarium with a tarantula in it. I am going to ask you to touch the tarantula, okay?

MEREL KINDT'S PATIENT: They are not poisonous, right?

MEREL KINDT: Well, tarantulas are poisonous.

Walk to the yellow line. Very good. You are doing very good.

NARRATOR: Just like with Nader's rats, the first step is to get Jeroen to draw up the memory of his fear.

MEREL KINDT: We ask our participants to approach the tarantula, which triggers the original fear memory.

How much distress do you feel right now?

MEREL KINDT'S PATIENT: Dry mouth; I feel shaking.

MEREL KINDT: You are doing very well. Try to look here. Don't avoid it. Stay here. It is important that you see it. Just put your hand here and stop. What do you think will happen? It is just a fear.

This approaching the spider makes the fear memory unstable,…

Okay, we go to the other side of the room.

…such that, if we give propranolol after the exposure to the tarantula, the drug can interfere with the re-stabilization of the original fear memory.

NARRATOR: Propanolol is a blood-pressure medication that blocks the release of noradrenaline in the amygdala, the fear center of the brain. Since noradrenaline is part of the brain's anxiety signal during a fearful event, blocking it after recall seems disrupt the reconsolidation, the fear part of the memory.

MEREL KINDT: What is very important is that it is not a "forget" pill. If we do not trigger the memory reactivation, the drug will not work.

NARRATOR: The next day Jeroen returns.

MEREL KINDT: We are going to do this again. We are going to go to the other side of the room, and I am going to ask you again to touch the spider.

You can touch it here, on the backside.

Very good. Did you feel it very good? Try it again.

MEREL KINDT'S PATIENT: It felt like rubber.

MEREL KINDT: Try it again. Very good.

Okay.

MEREL KINDT'S PATIENT: Okay.

MEREL KINDT: Can you try to….?

MEREL KINDT'S PATIENT: Hold it there?

MEREL KINDT: Yeah, with your finger.

MEREL KINDT'S PATIENT: Oh, wow.

MEREL KINDT: Very good. How much distress do you feel right now, from zero to 100?

MEREL KINDT'S PATIENT: Much less than yesterday.

MEREL KINDT: That is very impressive. Do it again.

NARRATOR: It takes a few tries, but after just minutes…

MEREL KINDT: Yes, very…yes, very good, very good, yes, yes. How does it feel to touch a tarantula?

MEREL KINDT'S PATIENT: Like touching a hamster.

Maybe he likes it.

NARRATOR: So far Kindt's repeated this work in over 30 people with spider phobia and other anxiety disorders and…

MEREL KINDT: The effects were so overwhelming that I did not believe them, initially.

NARRATOR: But, in fact, the therapy worked in every spider-phobe she tested, even a year later.

SASHA COHEN: It was unbelievable; just standing there, like, how could it be possible?

MEREL KINDT'S PATIENT: It's my new friend. It is really confusing.

It's like a contradiction with how I used to feel and how I feel. It is so strange, like I am someone else now.

MEREL KINDT: We, of course, cannot prove that we delete or even erase the original fear memory, because we can only observe the new behavior. But given that the fear does not come back, we hypothesize that the previously formed memories are in fact deleted.

NARRATOR: Treating people with spider phobia is only the first step. Kindt is now among a handful of scientists using reconsolidation to treat a variety of human disorders, from drug addiction to P.T.S.D. And though the research is in its infancy, early results have been promising.

MEREL KINDT: I am very hopeful that the reconsolidation intervention will be further developed for people with post-traumatic stress disorder.

NARRATOR: But reconsolidation is more than just a therapeutic tool. If the act of recalling a memory makes it vulnerable to change, it may also provide a biological explanation for something we've known all along, that our memory is often an unreliable narrator.

STEVE RAMIREZ: I could swear by every lie detector test that…

WOMAN: …I met Mother Teresa, but I hadn't.

MAN #1: …something that I wanted to happen, but it never did happen.

ELIZABETH LOFTUS (University of California, Irvine): I believe that my earliest memory was a very happy memory of going to a movie called The Greatest Show on Earth. And it wasn't until much later that I found out that the movie was released when I was eight years old. So, it couldn't have been my earliest memory.

NARRATOR: This comes as no surprise to Elizabeth Loftus. She's spent the last 40 years exploring exactly how unreliable our memory is.

ELIZABETH LOFTUS: I think people ought to pay more attention to the fact that there are memory errors all around them.

NARRATOR: Her work has inspired a generation of researchers, including psychologist Julia Shaw.

JULIA SHAW: The question isn't, "Do we have false memories?" It's, "How false are our memories?" There's so many things that can and do go wrong, along the way.

NARRATOR: To find out how wrong, Shaw has designed, perhaps, the most comprehensive study ever on false memory. She starts by recruiting over a hundred people for what they think is a study about their childhood memories.

JULIA SHAW: So this is my first meeting with the participant.

The first event is a time when you were twelve, when you moved from Trinidad to Kelowna with your family.

FALSE MEMORY PARTICIPANT: I hated the move.

NARRATOR: But, actually, the study is to see if it's possible to implant a false memory about committing a crime.

JULIA SHAW: I had colleagues saying, "This isn't going to work. There's no way you will get individuals to think that they committed a crime that never happened."

NARRATOR: She begins with a true event, gathered from their parents—in this case a family move.

FALSE MEMORY PARTICIPANT: We moved around every year, kind of thing.

NARRATOR: But this was just a trick to gain trust. The next step is to introduce the false memory—a fight so severe that the police were called.

JULIA SHAW: So, the other event that your parents report happening was, when you were 14 years old, you initiated a physical fight, and the police called your parents. They said it happened in Kelowna, in the fall, and you were with Ryan when it happened.

NARRATOR: Only two of the details are real: the name of the best friend and the place she lived at the time. The rest is made up.

FALSE MEMORY PARTICIPANT: Honestly, I don't remember. I don't know what you are talking about. I feel like I have never been in a fight. I'm so confused.

NARRATOR: She then turns to series of cognitive techniques known to induce false memories, starting with an imagination exercise.

JULIA SHAW: I'd like you to relax. Close your eyes, and focus your attention on trying to retrieve this memory.

FALSE MEMORY PARTICIPANT: Okay.

NARRATOR: Bolstered with a little social pressure…

JULIA SHAW: This might seem a bit strange but this does work for most people.

FALSE MEMORY PARTICIPANT: Okay.

JULIA SHAW: Subtly introducing this notion that it works for most people, if they try hard enough, which is a subtle form of social manipulation.

NARRATOR: …and one by one, asks the participant to visualize certain details of the story.

JULIA SHAW: Things that are easy to picture first.

Picture yourself at the age of fourteen,…

Picture yourself at the age of fourteen. That's an easy thing to picture.

In Kelowna.

…in Kelowna, the place that she lived at the age, also easy to picture….

And it's fall.

…It's fall. Everybody can picture fall.

And you were with Ryan when it happened.

DAN SCHACTER: When people imagine events that might have occurred in their past, we know that that's a potent way of creating a false memory.

NARRATOR: After giving the memory a week to set, she brings the participant back.

JULIA SHAW: Welcome back.

So, by the time we get to interview number two, we are seeing a different story.

FALSE MEMORY PARTICIPANT: I remember a verbal fight, and maybe…It seems so unlike…Maybe I pushed her or something?

JULIA SHAW: Good, okay.

So, this is where she first is buying into the idea that she actually had a fight.

FALSE MEMORY PARTICIPANT: I feel like she pushed me first.

JULIA SHAW: She is starting to picture how it could have happened. And what could have been, turns into what would have been, turns into what was.

NARRATOR: So by the third interview, the memory has taken hold.

FALSE MEMORY PARTICIPANT: I think the cops showed up, and we were having a, kind of, verbal fight, and it got to a push.

NARRATOR: And it wasn't just this once. Shaw was able to convince over 70 percent of her participants that they committed a crime.

MAN #1: I just lost it; couldn't take it anymore.

JULIA SHAW: I was incredibly surprised at the rate that I had in terms of successfully implanting these false memories.

…physically feel this?

And yet, there we were. And they just kept coming and coming and coming.

NARRATOR: So much so, Shaw's team cut the study short.

JULIA SHAW: Now, this is a false memory study.

FALSE MEMORY PARTICIPANT: What? I'm so embarrassed.

NARRATOR: And the ramifications go way beyond fooling college students. False memory studies, like this, question one of the cornerstones of the criminal justice system.

ELIZABETH LOFTUS: In those hundreds of cases where D.N.A. testing has proven that these individuals were wrongly convicted, about three-quarters of the time the convictions were based on faulty eyewitness testimony.

NARRATOR: So, if our memories are more malleable than we think, and we can change them, even erase some of them, what's next? Will there ever be day when, at just the push of a button, we can implant or edit specific memories at will.

Like in the movies?

LEONARDO DICAPRIO (as Dom Cobb, in Inception/Film Clip): The seed that we plant in this man's mind will grow into an idea. This idea will define him. It may come to change, it may come to change everything about him.

STEVE RAMIREZ: Movies like Inception, Total Recall, Eternal Sunshine…, of course they're possible. If mice had Hollywood, then it's possible, in practice, right now.

NARRATOR: In fact, here, at Columbia University, Christine Denny is one of a handful of neuroscientists who can do just that.

CHRISTINE DENNY: It does seem like a science fiction, but we are really doing Inception, in our lab, with turning on and off memories.

NARRATOR: It's called optogenetics, a technique so revolutionary it allows us to not only map a specific memory, but manipulate it with lasers—at least in these little guys.

These mice might not look so special,…

CHRISTINE DENNY: You could not tell my mice apart from a mouse on the street or wherever you would go to a pet store and buy a mouse. They don't look any different.

NARRATOR: …but they are. These are genetically modified mice that allow Denny to record specific memories and turn them on and off at will. To demonstrate, she starts by putting a mouse in a new environment.

CHRISTINE DENNY: You can see that the mouse is just sitting here, in the corner, freezing, basically, scared of the environment.

NARRATOR: That's because it's bright; there's no place to hide. But the goal isn't to frighten mice. She wants to see if she can override this fear by playing back a happy memory she recorded yesterday.

CHRISTINE DENNY: What we did is labeled a positive memory in the brains of these mice.

NARRATOR: Yesterday, this same mouse got to explore the kind of place it naturally likes: dimly lit, full of soft bedding, with a nice place to hide. And, while he was scurrying around, Denny recorded the exact neurons that fired when he made a memory of that pleasant place.

CHRISTINE DENNY: The cells that are labeled, here, in green, when I turn on the laser, those cells will turn on the memory.

NARRATOR: But how? How do you record a specific memory? And how do you get brain cells to respond to light? Here's where the sci-fi wizardry comes in.

CHRISTINE DENNY: We genetically engineered mice so that we can permanently label an individual memory.

NARRATOR: The key is this mouse's special genome: they're bred to carry a piece of D.N.A., from algae, that carries the code for a light-sensitive protein. In nature, that protein allows the algae to respond to light. In Denny's mice, it just sits there quietly in the mouse's genome, not doing anything, until…

CHRISTINE DENNY: You inject a drug, right before you expose them to this positive experience.

NARRATOR: …the drug switches that gene on, telling any brain cells that fire within the hour to install this light-sensitive protein on their surfaces. As the mouse is exploring a pleasant environment, any neurons that fire will leave a "footprint" of the memory in the mouse's brain. After the drug wears off, only those cells will respond to light, meaning…

CHRISTINE DENNY: It's basically like a switch. So what you can then do is use a laser to control these cells.

NARRATOR: These tiny fiber optics can shine light directly into the mouse's brain.

CHRISTINE DENNY: And so what we're going to try to do now is to turn on these cells that we've labeled, with a positive memory.

NARRATOR: Right now, the mouse is still scared, but, if Denny is right, the laser should activate the exact same neurons that fired when the mouse was making a happy memory, effectively causing it to relive that positive experience.

CHRISTINE DENNY: Okay, so watch, now, what happens when I'm going to turn this laser on. You can see that the animal's actually moving, smelling, grooming himself, which is a sign that he feels safe.

NARRATOR: But turn the laser off…

CHRISTINE DENNY: resumes his behavior, freezing in a corner.

NARRATOR: Denny can now trigger this memory at will. On…off…

CHRISTINE DENNY: I think, the first time we did it, we didn't believe it. When you see inside of the brains of these mice, and you can see how you're only manipulating those cells and changing the behavioral output of the animal, that's, yeah, science fiction.

DAN SCHACTER: This is potentially one of the most important new developments in memory research, because it suggests a level and precision of control over memory that we've really never seen before.

NARRATOR: A degree of precision many scientists think we might have over our memories someday.

STEVE RAMIREZ: I think that it's a matter of when this happens, not a matter of if it'll happen, in people.

NARRATOR: Which raises the question, if, by a flick of a switch, we could edit that first kiss or erase that argument with a spouse, would we want to?

MATT WALKER: What scientists, now, are starting to realize is that we can modify memories in some remarkable ways. The question is, how do we think about that? By starting to manipulate those memories, are we suggesting that evolution got it wrong?

NARRATOR: Could it be possible that our memories are built the way they are for a reason?

ELIZABETH LOFTUS: Why would we be constructed with a memory system that is so potentially open to suggestion and change?

NARRATOR: Perhaps Jake, the 11-year-old boy with the amazing memory, can help answer that question one day. After months of scans, scientists are still searching for something in his brain to explain his extraordinary ability, but even if they don't find anything, that would be an important clue.

NICO DOSENBACH: Jake's already telling us something about our memories, namely that the human brain has the capability to remember your entire life in great detail. It's a fascinating question of, "Why don't we?"

NARRATOR: Consider Jake. Though he and other H.S.A.M.s love having their special memories, even at his young age he is aware that it comes at a price.

JAKE HAUSLER: Just like to everything, there's an upside and a downside. The downside is you can't forget every bad thing that happens to you.

JIM MCGAUGH: They live in different worlds than, than the worlds that you and I live in. And you have to wonder, would you like to live in that world?

NARRATOR: A world where you can't forget?

ANDRÉ FENTON: Forgetting is probably one of the most important things that brains will do. Perhaps evolution was smart enough to design a system that stores only the stuff that's important.

NARRATOR: Could it be that what we think of as memory's flaws are actually part of its strength?

KELSEY MARTIN: Maybe we have a misconception of what the purpose of memory is, that we think of it more as an accurate recording of past experiences, as opposed to a creative process of combining our experiences over time.

MATT WALKER: Perhaps the ultimate goal of memory is not to retain every single fact that you've learned. If you had just this picture-perfect back catalogue, of 30, 40, 50, 60 years of experience, imagine how hard it would be to pick out the individual, specific experiences that you need at any one moment against the backdrop of that sea of noise.

NARRATOR: Somehow, this complex choreography of single cells adds up to our memory, a mysterious system that allows us to time-travel to the past and imagine our future. But perhaps memory's ultimate gift is a way to navigate that sea of noise, so we can pick out the experiences that each of us weave together to tell the story of our lives.