And so how did you respond? How did you did you go into therapy and did you start a grief group or did you first have a reaction to that?

Oh, for sure.

More of a of a reaction of like disbelief at first that, you know, the the idea that, you know, When we met in 2010, for instance, we agreed from the jump that everything that we did and everything that we were successful over, we were going to share.

That one plus one equals three, and that two brains working together are better than one, and that science doesn't have to be this individual isolation effort at all.

It can be the total opposite.

I love that.

Our dream was that when there's discoveries in science that we would be like the Situation Room in NASA where everyone's cheering when the rover lands on Mars, that kind of thing.

So maybe unpack that a little bit.

They may not be able to form new memories, so for example, where they're currently living, but they might be able to remember things from their past, like the lyrics to their favorite song from when they were 15 or, you know, the kind of example where somebody hits their head and they know who they are, but they won't recall the past two weeks.

Memories exist, I think, almost like a chain of dominoes, and then when we break an area like the hippocampus, it's like we take out one of those dominoes, and the chain reaction of recollection stops.

Um, another way I- I think about this, too, is that, uh, I think of memories as books in a library, and a librarian is the hippocampus, which helps us access those memories.

So when the hippocampus is damaged, this could be due to Alzheimer's or a stroke or an accident.

The books are still intact, like we still have the memories of our past experiences, but the librarian that we need to access those books is now not intact.

So on the one hand, that means that we have an accessibility issue, that we can't retrieve those memories of the past anymore.

Um, on the other hand, and a reason that I'm cautiously optimistic about where our field of memory is going is that at least in rodents, which share an evolutionarily conserved hippocampus with humans, it's one of the, to be honest, biggest success stories of the past decade and a half in neuroscience, in my opinion, which is that whether it's due to Alzheimer's or Parkinson's or brain cancer or addiction or sleep deprivation or the one kind of amnesia we all share, which is infantile amnesia, that we don't remember what we were doing really before we were three years of age, more or less, in every single one of those cases, we've been able to artificially retrieve a memory that was thought to be lost.

In what circumstances might you want to be able to manipulate memories?

Can you tell us what, what you found?

found?In 2012, we had found that there are cells in the brain that hold onto individual memories, which when artificially activated, is enough to jumpstart that memory itself.

So that was the first million-dollar finding that Xu and I had made, was that artificially activating a fraction of cells that held onto a memory is enough to jumpstart that memory.

In 2013, we went on to show that not only could we activate a memory, but we could activate a memory and incorporate new information into that memory, and that's what we called creating a false memory.

And the beauty of that is that it really set the stage, in my opinion, for, uh, one of the most potent and relevant and applicable findings in 2015 from our work, which was that could we activate memories in a way that would actually be beneficial for the organism, almost like a drug or a treatment that's used to try to restore health to the brain.

And what we did was we were able to artificially activate a positive memory in the mouse brain to curb symptoms associated with depression and anxiety.

Uh, and that worked.

To what extent did grief and addiction inform your view of what memory is, and to what extent did your knowledge of what memory is help you analyze your grief and addiction?

perception about the usefulness of eyewitness testimony if you have two different people that come in one person who's absolutely certain that they saw something the other person that is maybe unsure they thought they think they might have seen something but you know they doubt they're doubtful um is it dangerous that we sometimes have a tendency to trust the person that is absolutely certain more than the person that's a little uh you know unsure of what they saw

It unfortunately can be dangerous, but it can also be the right thing to do.

And I think that that's where neuroscience and the law truly have a lot to learn from each other.

There's a fantastic perspective piece by Dan Schachter and Elizabeth Loftus called Neuroscience and the law or neuroscience and eyewitness testimony what neuroscience can learn from the law or vice versa like you put in those keywords in google and you'll find it um now to me what it says is how we use memory and when we use it really matters if i'm using a memory right now to try to gratitude journal for 10 minutes to feel good and a bit more upbeat about the day that has a very clear bounded purpose that I'm using right now that is of consequence in a positive direction.

In the court of law, in my opinion, we shouldn't throw the baby out with the bathwater, so to speak.

We need to rely on eyewitness testimony as part of submissible evidence, of course, because oftentimes that's all we have.

On the other hand, It's okay to take memory with a grain of salt, but without getting rid of it entirely.

Memory is just something that seems to almost appear or bubble up through us in a very unexpected way.

Um, i-is it dangerous that we sometimes have a tendency to trust the person that is absolutely certain more than the person that's a little, uh, you know, unsure of what they saw?

It, it unfortunately can be dangerous, but it can also be the right thing to do.

And I think that that's where, like, neuroscience and the law truly have a lot to learn from each other.

There's a fantastic perspective piece by Dan Schacter and Elizabeth Loftus called Neuroscience and the Law or Neuroscience and Eyewitness Testimony: What Neuroscience Can Learn From the Law or vice versa.

Like, I-- You put in those keywords in Google and you'll find it.

Um, now, to me, what it says is how we use memory and when we use it really matters.

If I'm using a memory right now to try to gratitude journal for 10 minutes to feel good and a bit more upbeat about the day, that has a very clear bounded purpose that I'm using right now that is, um, of consequence in a positive direction.

Um, so w-why is it that memory seems to work this way, where it's like we don't necessarily have control over why-- when we're remembering something, memory is just something that seems to, you know, almost appear or come, come bubble up through us in a, in a way, in a very unexpected way?

Um, i-i-is it dangerous that we sometimes have a tendency to trust the person that is absolutely certain more than the person that's a little, uh, you know, unsure of what they saw?

It, it unfortunately can be dangerous, but it can also be the right thing to do.

And I think that that's where, like, neuroscience and the law truly have a lot to learn from each other.

There's a fantastic perspective piece by Dan Schacter and Elizabeth Loftus called Neuroscience and the Law or Neuroscience and Eyewitness Testimony: What Neuroscience Can Learn From the Law or vice versa.

Like, I-- You put in those keywords in Google and you'll find it.

Um, now, to me, what it says is how we use memory and when we use it really matters.

If I'm using a memory right now to try to gratitude journal for ten minutes to feel good and a bit more upbeat about the day, that has a very clear bounded purpose that I'm using right now that is, um, of consequence in a positive direction.

Memory is just something that seems to, you know, almost appear or come, come bubble up through us in a, in a way, in a very unexpected way.

perception about the usefulness of eyewitness testimony if you have two different people that come in one person who's absolutely certain that they saw something the other person that is maybe unsure they thought they think they might have seen something but you know they doubt they're doubtful um is it dangerous that we sometimes have a tendency to trust the person that is absolutely certain more than the person that's a little uh you know unsure of what they saw

It unfortunately can be dangerous, but it can also be the right thing to do.

And I think that that's where neuroscience and the law truly have a lot to learn from each other.

There's a fantastic perspective piece by Dan Schachter and Elizabeth Loftus called Neuroscience and the law or neuroscience and eyewitness testimony what neuroscience can learn from the law or vice versa like you put in those keywords in google and you'll find it um now to me what it says is how we use memory and when we use it really matters if i'm using a memory right now to try to gratitude journal for 10 minutes to feel good and a bit more upbeat about the day that has a very clear bounded purpose that I'm using right now that is of consequence in a positive direction.

In the court of law, in my opinion, we shouldn't throw the baby out with the bathwater, so to speak.

We need to rely on eyewitness testimony as part of submissible evidence, of course, because oftentimes that's all we have.

On the other hand, It's okay to take memory with a grain of salt, but without getting rid of it entirely.

Memory is just something that seems to almost appear or bubble up through us in a very unexpected way.

perception about the usefulness of eyewitness testimony if you have two different people that come in one person who's absolutely certain that they saw something the other person that is maybe unsure they thought they think they might have seen something but you know they doubt they're doubtful um is it dangerous that we sometimes have a tendency to trust the person that is absolutely certain more than the person that's a little uh you know unsure of what they saw

It unfortunately can be dangerous, but it can also be the right thing to do.

And I think that that's where neuroscience and the law truly have a lot to learn from each other.

There's a fantastic perspective piece by Dan Schachter and Elizabeth Loftus called Neuroscience and the law or neuroscience and eyewitness testimony what neuroscience can learn from the law or vice versa like you put in those keywords in google and you'll find it um now to me what it says is how we use memory and when we use it really matters if i'm using a memory right now to try to gratitude journal for 10 minutes to feel good and a bit more upbeat about the day that has a very clear bounded purpose that I'm using right now that is of consequence in a positive direction.

In the court of law, in my opinion, we shouldn't throw the baby out with the bathwater, so to speak.

We need to rely on eyewitness testimony as part of submissible evidence, of course, because oftentimes that's all we have.

On the other hand, It's okay to take memory with a grain of salt, but without getting rid of it entirely.

Memory is just something that seems to almost appear or bubble up through us in a very unexpected way.

Can you give us a more in-depth explanation of the book's title and how it relates to the envisioned global trilogy of outdoor nature and fly fishing literature?

Sure.

I select all these titles myself and design these things myself, and there's always a reason behind it.

So this title, A Season in Patagonia, I'm not talking about a fishing season.

I'm not talking about a season like summer, winter, fall.

It's a season in a, in this case, a man's life, a season in a person's life, a season of discovery.

And that's what this whole book is about, discovery, and I use the metaphor of following the conquistadors, traveling and discovering also as my own journey.

Was there a moment when you realized you were in an ecosystem unlike anywhere else you've ever fished? Was it that moment?

But, you know, given that memories make up who we are, w- does that sort of dull who we are in doing that? Should we not be messing with the pain of a breakup?

Right.

Um, great question.

My, my way of thinking about this is that the field of memory manipulation needs to have an ethically bounded goal in mind, like, why are we doing this? Presumably, the why isn't so that we could go into high school Steve's brain and get rid of the memory of a breakup that I was gonna get over in two weeks kind of thing.

It would be for the person that is living with a given disorder that's impairing their day-to-day ability to do the things that they wanna do, socialize, go out into the real world, and so on and so forth.

If the goal is to restore health and well-being to the individual, then we would presumably think of memory manipulation as just one of many tools in our Swiss Army knife of toolkits that we have to go in to alleviate the brain and to help the brain heal, for that matter.

Some of the science at least says that, I think it's about 80% of people would not wanna have any aspect of their past modified or edited or so on.

You also write really openly in the book about your own struggle with addiction, and I wonder how memory feeds into that, and how studying memory or altering memories could maybe help people who are struggling with addiction.

You coped with it in a way that I'm sure you wouldn't recommend to many other people, descending into alcoholism.

Yeah, exactly.

And that, I think, really... underscored to me just how powerful memories really are.

So to rewind a little bit, when my former, he was a postdoctoral fellow in the lab of Susumu Tonegawa when I was a graduate student at MIT, Shu Liu was my friend and mentor throughout all of graduate school, and we did that TED Talk together.

And we both kind of poked fun at this idea that even though we were both next to each other for the talk, and we both rehearsed the same exact talk, our memory and experience of that 15 minutes are so different than each other's.

Like my experience is so different than his experience and my memory of those moments are very different than his memories were of those moments.

I was a nervous wreck, but also outwardly excited.

I asked him if by recalling his friend and mentor, Shu Li Yu, and remembering the best of their time together, he could change the focus of the memory so that the pain could be overridden by pleasure.

How do you establish memories in mice, and then how do you manipulate them?

Yeah, so there's a handful of ways of doing it reliably, and one of the ways that we started off with was by exposing our animals to what we call a context, which is essentially a box the size of a shoebox that these animals go and explore, and we teach them something in that box.

We can teach them, for example, that a particular part of that box is negative.

So if the animals get some aversive stimuli that they temporarily won't like, then they'll learn to avoid that part of the box.

It's kind of like going to a restaurant and getting food poisoning.

You're very unlikely to go back there anytime soon.

Alternatively, we can also go in and say, well, if the animal goes to this corner of the box and Let's give them a bit of a food reward.

Well, if we're changing the memories when we recall them, how much can we actually trust our memories?

Same time too, you know, there's also the flip side of it, of making someone or helping people, especially those who suffer from things like PTSD, um, Could you talk about some of the research that is done, some of the clinical applications that people are looking into for this false memory creation?

Definitely.

The thing that stems from creating false memories is not so much the false aspect of it, but the fact that we could rewrite the contents of a memory in a positive direction or in a negative direction or really in any which direction to update the contents of that memory.

And we think that that has tremendous therapeutic value.

Now, to take a step back, you know, I give this example or I think of this example a lot of Something as elemental and nourishing as water can be used to nourish ourselves and to give us livelihood.

Or it could be used to torture someone.

So something that simple can be used for good or bad.

How do you think about the future of this development in terms of the ability for us to actually have almost super memories?

Same time too, you know, there's also the flip side of it, of making someone or helping people, especially those who suffer from things like PTSD, um, Could you talk about some of the research that is done, some of the clinical applications that people are looking into for this false memory creation?

Definitely.

The thing that stems from creating false memories is not so much the false aspect of it, but the fact that we could rewrite the contents of a memory in a positive direction or in a negative direction or really in any which direction to update the contents of that memory.

And we think that that has tremendous therapeutic value.

Now, to take a step back, you know, I give this example or I think of this example a lot of Something as elemental and nourishing as water can be used to nourish ourselves and to give us livelihood.

Or it could be used to torture someone.

So something that simple can be used for good or bad.

How do you think about the future of this development in terms of the ability for us to actually have almost super memories?

The more you remember something, like if there's a memory that you run through your head over and over again, does the process of recollection do something to the memory? Does it either make it better because you're, like, sharpening it 'cause you're remembering it over and over again? Or does the process of recollection distort it?

One of the sort of inconvenient truths of this all I thought was captured beautifully by, um, Daniela Schiller is a professor at Mount Sinai in New York, and she was giving a talk once and said that the inconvenient truth of this is that the memories that we hold dear, the ones that are the most real memories in our brain, are the ones that we don't recall because those are the ones that are left untarnished by the process of recollection.

To me, what that means is that, yeah, the memories that we don't recall, like maybe the memories that you haven't thought of in decades, the first time you recall it is the most real that you will experience that memory.

And then the second and third and fourth time, it's not that it's less real, it's just warped a bit more.

And it doesn't even have to be warped to the point of becoming a false memory per se.

It could just be that the different, again, the hues and contours and emotions and, and how we felt about that memory can also change.

Um, I think about this personally often when I'm sometimes...

And so when people talk about dementia, Alzheimer's, and people don't remember things, is the memory gone or is it in there and this is the kind of thing you do when trying to manipulate it to bring it back or ... wh- what? Where, where's that memory?

What kind of memory manipulation is actually possible? I mean, we're not talking about Inception-like capabilities, right?

Right.

Well, it depends if you're a, a mouse or a fly or a human, in this case.

Uh, to start with the mice work, because it's the kind of work that my lab does, it is Inception and it is Severance.

And that's the amazing thing, is that there, there's so much that we can do in 2025 in rodent research that I like to think is a blueprint for what we can do in humans, hopefully soon, in a way that can be used to restore health in the brain.

So for example, my last project in grad school that I talk about in the book was a project where the goal was to artificially activate positive memories.

And we were able to do that.

Could, could you not make that happen in people too?