WEBVTT

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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

00:11:19.313 --> 00:11:21.220
this "play" button of the clip

00:11:21.244 --> 00:11:25.805
so that we can play this video
clip any time, anywhere.

00:11:25.829 --> 00:11:28.336
But is there a possibility
that we can actually get

00:11:28.360 --> 00:11:31.196
inside the brain and edit this movie clip

00:11:31.220 --> 00:11:34.092
so that we can make it
different from the original?

00:11:34.116 --> 00:11:36.270
Yes we can.

00:11:36.294 --> 00:11:38.485
Turned out that all we need
to do is basically

00:11:38.509 --> 00:11:42.675
reactivate a memory using
lasers just like we did before,

00:11:42.699 --> 00:11:46.114
but at the same time,
if we present new information

00:11:46.138 --> 00:11:50.088
and allow this new information
to incorporate into this old memory,

00:11:50.112 --> 00:11:52.526
this will change the memory.

00:11:52.550 --> 00:11:56.189
It's sort of like making a remix tape.

00:11:56.213 --> 00:11:59.047
SR: So how do we do this?

00:11:59.071 --> 00:12:01.004
Rather than finding a fear
memory in the brain,

00:12:01.028 --> 00:12:02.720
we can start by taking our animals,

00:12:02.744 --> 00:12:05.697
and let's say we put them in a blue
box like this blue box here

00:12:05.721 --> 00:12:08.344
and we find the brain cells
that represent that blue box

00:12:08.368 --> 00:12:10.607
and we trick them to respond
to pulses of light

00:12:10.631 --> 00:12:12.341
exactly like we had said before.

00:12:12.365 --> 00:12:14.465
Now the next day, we can take
our animals and place them

00:12:14.489 --> 00:12:17.164
in a red box that they've never
experienced before.

00:12:17.188 --> 00:12:19.427
We can shoot light
into the brain to reactivate

00:12:19.451 --> 00:12:21.299
the memory of the blue box.

00:12:21.323 --> 00:12:23.043
So what would happen here
if, while the animal

00:12:23.067 --> 00:12:24.972
is recalling the memory of the blue box,

00:12:24.996 --> 00:12:27.580
we gave it a couple of mild foot shocks?

00:12:27.604 --> 00:12:30.273
So here we're trying to artificially
make an association

00:12:30.297 --> 00:12:32.188
between the memory of the blue box

00:12:32.212 --> 00:12:33.691
and the foot shocks themselves.

00:12:33.715 --> 00:12:35.477
We're just trying to connect the two.

00:12:35.501 --> 00:12:37.013
So to test if we had done so,

00:12:37.037 --> 00:12:38.341
we can take our animals once again

00:12:38.365 --> 00:12:40.287
and place them back in the blue box.

00:12:40.311 --> 00:12:43.026
Again, we had just reactivated
the memory of the blue box

00:12:43.050 --> 00:12:45.431
while the animal got a couple
of mild foot shocks,

00:12:45.455 --> 00:12:47.562
and now the animal suddenly freezes.

00:12:47.586 --> 00:12:50.920
It's as though it's recalling being
mildly shocked in this environment

00:12:50.944 --> 00:12:53.766
even though that never actually happened.

00:12:53.790 --> 00:12:55.628
So it formed a false memory,

00:12:55.652 --> 00:12:57.700
because it's falsely
fearing an environment

00:12:57.724 --> 00:12:59.058
where, technically speaking,

00:12:59.082 --> 00:13:01.242
nothing bad actually happened to it.

00:13:01.266 --> 00:13:03.695
XL: So, so far we are only talking about

00:13:03.719 --> 00:13:06.061
this light-controlled "on" switch.

00:13:06.085 --> 00:13:09.349
In fact, we also have
a light-controlled "off" switch,

00:13:09.373 --> 00:13:11.429
and it's very easy to imagine that

00:13:11.453 --> 00:13:13.907
by installing this
light-controlled "off" switch,

00:13:13.931 --> 00:13:19.495
we can also turn off a memory,
any time, anywhere.

00:13:19.519 --> 00:13:21.709
So everything
we've been talking about today

00:13:21.733 --> 00:13:26.386
is based on this philosophically
charged principle of neuroscience

00:13:26.410 --> 00:13:30.504
that the mind, with its seemingly
mysterious properties,

00:13:30.528 --> 00:13:34.149
is actually made of physical
stuff that we can tinker with.

00:13:34.173 --> 00:13:35.624
SR: And for me personally,

00:13:35.648 --> 00:13:37.410
I see a world where we can reactivate

00:13:37.434 --> 00:13:39.321
any kind of memory that we'd like.

00:13:39.345 --> 00:13:42.619
I also see a world where we can
erase unwanted memories.

00:13:42.643 --> 00:13:44.786
Now, I even see a world
where editing memories

00:13:44.810 --> 00:13:46.094
is something of a reality,

00:13:46.118 --> 00:13:47.799
because we're living in a time
where it's possible

00:13:47.823 --> 00:13:50.252
to pluck questions from the tree
of science fiction

00:13:50.276 --> 00:13:52.444
and to ground them
in experimental reality.

00:13:52.468 --> 00:13:54.327
XL: Nowadays, people in the lab

00:13:54.351 --> 00:13:56.713
and people in other
groups all over the world

00:13:56.737 --> 00:14:00.530
are using similar methods
to activate or edit memories,

00:14:00.554 --> 00:14:04.371
whether that's old or new,
positive or negative,

00:14:04.395 --> 00:14:07.043
all sorts of memories so
that we can understand

00:14:07.067 --> 00:14:08.907
how memory works.

00:14:08.931 --> 00:14:10.691
SR: For example, one group in our lab

00:14:10.715 --> 00:14:13.329
was able to find the brain cells
that make up a fear memory

00:14:13.353 --> 00:14:16.104
and converted them into a pleasurable
memory, just like that.

00:14:16.128 --> 00:14:19.271
That's exactly what I mean about editing
these kinds of processes.

00:14:19.295 --> 00:14:21.534
Now one dude in lab
was even able to reactivate

00:14:21.558 --> 00:14:23.479
memories of female mice in male mice,

00:14:23.503 --> 00:14:26.474
which rumor has it
is a pleasurable experience.

00:14:26.498 --> 00:14:30.591
XL: Indeed, we are living
in a very exciting moment

00:14:30.615 --> 00:14:34.396
where science doesn't have
any arbitrary speed limits

00:14:34.420 --> 00:14:37.583
but is only bound by our own imagination.

00:14:37.607 --> 00:14:39.750
SR: And finally, what do
we make of all this?

00:14:39.774 --> 00:14:41.701
How do we push this technology forward?

00:14:41.725 --> 00:14:43.916
These are the questions
that should not remain

00:14:43.940 --> 00:14:45.213
just inside the lab,

00:14:45.237 --> 00:14:47.809
and so one goal of today's talk
was to bring everybody

00:14:47.833 --> 00:14:50.214
up to speed with the kind
of stuff that's possible

00:14:50.238 --> 00:14:51.488
in modern neuroscience,

00:14:51.512 --> 00:14:52.998
but now, just as importantly,

00:14:53.022 --> 00:14:56.330
to actively engage everybody
in this conversation.

00:14:56.354 --> 00:14:59.116
So let's think together as a team
about what this all means

00:14:59.140 --> 00:15:01.133
and where we can and should go from here,

00:15:01.157 --> 00:15:03.231
because Xu and I think we all have

00:15:03.255 --> 00:15:05.767
some really big decisions ahead of us.

00:15:05.791 --> 00:15:06.892
Thank you. XL: Thank you.

00:15:06.916 --> 00:15:08.550
(Applause)