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Steve Ramirez: My first year of grad school,

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I found myself in my bedroom

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eating lots of Ben & Jerry's

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watching some trashy TV

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and maybe, maybe listening to Taylor Swift.

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I had just gone through a breakup.

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(Laughter)

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So for the longest time, all I would do

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is recall the memory of this person over and over again,

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wishing that I could get rid of that gut-wrenching,

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visceral "blah" feeling.

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Now, as it turns out, I'm a neuroscientist,

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so I knew that the memory of that person

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and the awful, emotional undertones that color in that memory,

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are largely mediated by separate brain systems.

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And so I thought, what if we could go into the brain

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and edit out that nauseating feeling

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but while keeping the memory of that person intact?

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Then I realized, maybe that's a little bit lofty for now.

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So what if we could start off by going into the brain

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and just finding a single memory to begin with?

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Could we jump-start that memory back to life,

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maybe even play with the contents of that memory?

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All that said, there is one person in the entire world right now

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that I really hope is not watching this talk.

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(Laughter)

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So there is a catch. There is a catch.

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These ideas probably remind you of "Total Recall,"

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"Eternal Sunshine of the Spotless Mind,"

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or of "Inception."

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But the movie stars that we work with

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are the celebrities of the lab.

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Xu Liu: Test mice.

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(Laughter)

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As neuroscientists, we work in the lab with mice

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trying to understand how memory works.

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And today, we hope to convince you that now

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we are actually able to activate a memory in the brain

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at the speed of light.

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To do this, there's only two simple steps to follow.

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First, you find and label a memory in the brain,

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and then you activate it with a switch.

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As simple as that.

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(Laughter)

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SR: Are you convinced?

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So, turns out finding a memory in the brain isn't all that easy.

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XL: Indeed. This is way more difficult than, let's say,

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finding a needle in a haystack,

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because at least, you know, the needle is still something

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you can physically put your fingers on.

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But memory is not.

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And also, there's way more cells in your brain

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than the number of straws in a typical haystack.

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So yeah, this task does seem to be daunting.

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But luckily, we got help from the brain itself.

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It turned out that all we need to do is basically

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to let the brain form a memory,

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and then the brain will tell us which cells are involved

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in that particular memory.

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SR: So what was going on in my brain

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while I was recalling the memory of an ex?

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If you were to just completely ignore human ethics for a second

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and slice up my brain right now,

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you would see that there was an amazing number

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of brain regions that were active while recalling that memory.

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Now one brain region that would be robustly active

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in particular is called the hippocampus,

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which for decades has been implicated in processing

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the kinds of memories that we hold near and dear,

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which also makes it an ideal target to go into

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and to try and find and maybe reactivate a memory.

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XL: When you zoom in into the hippocampus,

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of course you will see lots of cells,

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but we are able to find which cells are involved

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in a particular memory,

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because whenever a cell is active,

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like when it's forming a memory,

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it will also leave a footprint that will later allow us to know

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these cells are recently active.

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SR: So the same way that building lights at night

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let you know that somebody's probably working there at any given moment,

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in a very real sense, there are biological sensors

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within a cell that are turned on

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only when that cell was just working.

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They're sort of biological windows that light up

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to let us know that that cell was just active.

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XL: So we clipped part of this sensor,

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and attached that to a switch to control the cells,

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and we packed this switch into an engineered virus

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and injected that into the brain of the mice.

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So whenever a memory is being formed,

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any active cells for that memory

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will also have this switch installed.

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SR: So here is what the hippocampus looks like

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after forming a fear memory, for example.

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The sea of blue that you see here

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are densely packed brain cells,

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but the green brain cells,

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the green brain cells are the ones that are holding on

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to a specific fear memory.

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So you are looking at the crystallization

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of the fleeting formation of fear.

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You're actually looking at the cross-section of a memory right now.

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XL: Now, for the switch we have been talking about,

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ideally, the switch has to act really fast.

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It shouldn't take minutes or hours to work.

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It should act at the speed of the brain, in milliseconds.

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SR: So what do you think, Xu?

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Could we use, let's say, pharmacological drugs

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to activate or inactivate brain cells?

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XL: Nah. Drugs are pretty messy. They spread everywhere.

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And also it takes them forever to act on cells.

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So it will not allow us to control a memory in real time.

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So Steve, how about let's zap the brain with electricity?

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SR: So electricity is pretty fast,

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but we probably wouldn't be able to target it

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to just the specific cells that hold onto a memory,

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and we'd probably fry the brain.

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XL: Oh. That's true. So it looks like, hmm,

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indeed we need to find a better way

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to impact the brain at the speed of light.

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SR: So it just so happens that light travels at the speed of light.

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So maybe we could activate or inactive memories

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by just using light --

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XL: That's pretty fast.

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SR: -- and because normally brain cells

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don't respond to pulses of light,

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so those that would respond to pulses of light

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are those that contain a light-sensitive switch.

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Now to do that, first we need to trick brain cells

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to respond to laser beams.

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XL: Yep. You heard it right.

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We are trying to shoot lasers into the brain.

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(Laughter)

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SR: And the technique that lets us do that is optogenetics.

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Optogenetics gave us this light switch that we can use

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to turn brain cells on or off,

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and the name of that switch is channelrhodopsin,

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seen here as these green dots attached to this brain cell.

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You can think of channelrhodopsin as a sort of light-sensitive switch

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that can be artificially installed in brain cells

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so that now we can use that switch

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to activate or inactivate the brain cell simply by clicking it,

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and in this case we click it on with pulses of light.

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XL: So we attach this light-sensitive switch of channelrhodopsin

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to the sensor we've been talking about

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and inject this into the brain.

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So whenever a memory is being formed,

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any active cell for that particular memory

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will also have this light-sensitive switch installed in it

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so that we can control these cells

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by the flipping of a laser just like this one you see.

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SR: So let's put all of this to the test now.

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What we can do is we can take our mice

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and then we can put them in a box that looks exactly like this box here,

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and then we can give them a very mild foot shock

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so that they form a fear memory of this box.

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They learn that something bad happened here.

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Now with our system, the cells that are active

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in the hippocampus in the making of this memory,

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only those cells will now contain channelrhodopsin.

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XL: When you are as small as a mouse,

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it feels as if the whole world is trying to get you.

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So your best response of defense

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is trying to be undetected.

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Whenever a mouse is in fear,

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it will show this very typical behavior

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by staying at one corner of the box,

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trying to not move any part of its body,

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and this posture is called freezing.

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So if a mouse remembers that something bad happened in this box,

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and when we put them back into the same box,

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it will basically show freezing

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because it doesn't want to be detected

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by any potential threats in this box.

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SR: So you can think of freezing as,

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you're walking down the street minding your own business,

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and then out of nowhere you almost run into

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an ex-girlfriend or ex-boyfriend,

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and now those terrifying two seconds

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where you start thinking, "What do I do? Do I say hi?

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Do I shake their hand? Do I turn around and run away?

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Do I sit here and pretend like I don't exist?"

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Those kinds of fleeting thoughts that physically incapacitate you,

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that temporarily give you that deer-in-headlights look.

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XL: However, if you put the mouse in a completely different

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new box, like the next one,

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it will not be afraid of this box

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because there's no reason that it will be afraid of this new environment.

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But what if we put the mouse in this new box

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but at the same time, we activate the fear memory

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using lasers just like we did before?

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Are we going to bring back the fear memory

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for the first box into this completely new environment?

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SR: All right, and here's the million-dollar experiment.

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Now to bring back to life the memory of that day,

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I remember that the Red Sox had just won,

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it was a green spring day,

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perfect for going up and down the river

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and then maybe going to the North End

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to get some cannolis, #justsaying.

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Now Xu and I, on the other hand,

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were in a completely windowless black room

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not making any ocular movement that even remotely resembles an eye blink

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because our eyes were fixed onto a computer screen.

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We were looking at this mouse here trying to activate a memory

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for the first time using our technique.

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XL: And this is what we saw.

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When we first put the mouse into this box,

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it's exploring, sniffing around, walking around,

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minding its own business,

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because actually by nature,

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mice are pretty curious animals.

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They want to know, what's going on in this new box?

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It's interesting.

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But the moment we turned on the laser, like you see now,

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all of a sudden the mouse entered this freezing mode.

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It stayed here and tried not to move any part of its body.

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Clearly it's freezing.

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So indeed, it looks like we are able to bring back

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the fear memory for the first box

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in this completely new environment.

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While watching this, Steve and I

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are as shocked as the mouse itself.

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(Laughter)

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So after the experiment, the two of us just left the room

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without saying anything.

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After a kind of long, awkward period of time,

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Steve broke the silence.

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SR: "Did that just work?"

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XL: "Yes," I said. "Indeed it worked!"

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We're really excited about this.

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And then we published our findings

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in the journal Nature.

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Ever since the publication of our work,

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we've been receiving numerous comments

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from all over the Internet.

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Maybe we can take a look at some of those.

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["OMGGGGG FINALLY... so much more to come, virtual reality, neural manipulation, visual dream emulation... neural coding, 'writing and re-writing of memories', mental illnesses. Ahhh the future is awesome"]

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SR: So the first thing that you'll notice is that people

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have really strong opinions about this kind of work.

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Now I happen to completely agree with the optimism

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of this first quote,

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because on a scale of zero to Morgan Freeman's voice,

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it happens to be one of the most evocative accolades

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that I've heard come our way.

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(Laughter)

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But as you'll see, it's not the only opinion that's out there.

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["This scares the hell out of me... What if they could do that easily in humans in a couple of years?! OH MY GOD WE'RE DOOMED"]

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XL: Indeed, if we take a look at the second one,

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I think we can all agree that it's, meh,

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probably not as positive.

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But this also reminds us that,

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although we are still working with mice,

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it's probably a good idea to start thinking and discussing

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about the possible ethical ramifications

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of memory control.

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SR: Now, in the spirit of the third quote,

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we want to tell you about a recent project that we've been

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working on in lab that we've called Project Inception.

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["They should make a movie about this. Where they plant ideas into peoples minds, so they can control them for their own personal gain. We'll call it: Inception."]

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So we reasoned that now that we can reactivate a memory,

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what if we do so but then begin to tinker with that memory?

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Could we possibly even turn it into a false memory?

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XL: So all memory is sophisticated and dynamic,

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but if just for simplicity, let's imagine memory

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as a movie clip.

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So far what we've told you is basically we can control

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this "play" button of the clip

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so that we can play this video clip any time, anywhere.

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But is there a possibility that we can actually get

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inside the brain and edit this movie clip

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so that we can make it different from the original?

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Yes we can.

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Turned out that all we need to do is basically

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reactivate a memory using lasers just like we did before,

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but at the same time, if we present new information

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and allow this new information to incorporate into this old memory,

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this will change the memory.

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It's sort of like making a remix tape.

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SR: So how do we do this?

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Rather than finding a fear memory in the brain,

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we can start by taking our animals,

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and let's say we put them in a blue box like this blue box here

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and we find the brain cells that represent that blue box

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and we trick them to respond to pulses of light

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exactly like we had said before.

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Now the next day, we can take our animals and place them

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in a red box that they've never experienced before.

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We can shoot light into the brain to reactivate

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the memory of the blue box.

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So what would happen here if, while the animal

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is recalling the memory of the blue box,

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we gave it a couple of mild foot shocks?

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So here we're trying to artificially make an association

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between the memory of the blue box

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and the foot shocks themselves.

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We're just trying to connect the two.

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So to test if we had done so,

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we can take our animals once again

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and place them back in the blue box.

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Again, we had just reactivated the memory of the blue box

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while the animal got a couple of mild foot shocks,

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and now the animal suddenly freezes.

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It's as though it's recalling being mildly shocked in this environment

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even though that never actually happened.

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So it formed a false memory,

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because it's falsely fearing an environment

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where, technically speaking,

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nothing bad actually happened to it.

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XL: So, so far we are only talking about

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this light-controlled "on" switch.

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In fact, we also have a light-controlled "off" switch,

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and it's very easy to imagine that

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by installing this light-controlled "off" switch,

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we can also turn off a memory, any time, anywhere.

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So everything we've been talking about today

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is based on this philosophically charged principle of neuroscience

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that the mind, with its seemingly mysterious properties,

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is actually made of physical stuff that we can tinker with.

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SR: And for me personally,

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I see a world where we can reactivate

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any kind of memory that we'd like.

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I also see a world where we can erase unwanted memories.

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Now, I even see a world where editing memories

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is something of a reality,

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because we're living in a time where it's possible

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to pluck questions from the tree of science fiction

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and to ground them in experimental reality.

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XL: Nowadays, people in the lab

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and people in other groups all over the world

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are using similar methods to activate or edit memories,

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whether that's old or new, positive or negative,

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all sorts of memories so that we can understand

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how memory works.

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SR: For example, one group in our lab

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was able to find the brain cells that make up a fear memory

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and converted them into a pleasurable memory, just like that.

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That's exactly what I mean about editing these kinds of processes.

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Now one dude in lab was even able to reactivate

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memories of female mice in male mice,

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which rumor has it is a pleasurable experience.

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XL: Indeed, we are living in a very exciting moment

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where science doesn't have any arbitrary speed limits

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but is only bound by our own imagination.

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SR: And finally, what do we make of all this?

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How do we push this technology forward?

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These are the questions that should not remain

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just inside the lab,

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and so one goal of today's talk was to bring everybody

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up to speed with the kind of stuff that's possible

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in modern neuroscience,

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but now, just as importantly,

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to actively engage everybody in this conversation.

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So let's think together as a team about what this all means

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and where we can and should go from here,

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because Xu and I think we all have

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some really big decisions ahead of us.

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Thank you.
XL: Thank you.

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(Applause)