Sebastian Seung: I am my connectome

247,777 views ・ 2010-09-28

TED


Please double-click on the English subtitles below to play the video.

00:17
We live in in a remarkable time,
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the age of genomics.
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Your genome is the entire sequence of your DNA.
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Your sequence and mine are slightly different.
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That's why we look different.
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I've got brown eyes;
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you might have blue or gray.
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But it's not just skin-deep.
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The headlines tell us
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that genes can give us scary diseases,
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maybe even shape our personality,
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or give us mental disorders.
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Our genes seem to have
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awesome power over our destinies.
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And yet, I would like to think
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that I am more than my genes.
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What do you guys think?
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Are you more than your genes?
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(Audience: Yes.) Yes?
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I think some people agree with me.
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I think we should make a statement.
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I think we should say it all together.
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All right: "I'm more than my genes" -- all together.
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Everybody: I am more than my genes.
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01:27
(Cheering)
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01:30
Sebastian Seung: What am I?
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01:32
(Laughter)
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I am my connectome.
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01:40
Now, since you guys are really great,
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maybe you can humor me and say this all together too.
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(Laughter)
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Right. All together now.
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Everybody: I am my connectome.
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SS: That sounded great.
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You know, you guys are so great, you don't even know what a connectome is,
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and you're willing to play along with me.
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I could just go home now.
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Well, so far only one connectome is known,
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that of this tiny worm.
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Its modest nervous system
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consists of just 300 neurons.
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And in the 1970s and '80s,
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a team of scientists
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mapped all 7,000 connections
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between the neurons.
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In this diagram, every node is a neuron,
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and every line is a connection.
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This is the connectome
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of the worm C. elegans.
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Your connectome is far more complex than this
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because your brain
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contains 100 billion neurons
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and 10,000 times as many connections.
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There's a diagram like this for your brain,
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but there's no way it would fit on this slide.
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Your connectome contains one million times more connections
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than your genome has letters.
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That's a lot of information.
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What's in that information?
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We don't know for sure, but there are theories.
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Since the 19th century, neuroscientists have speculated
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that maybe your memories --
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the information that makes you, you --
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maybe your memories are stored
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in the connections between your brain's neurons.
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And perhaps other aspects of your personal identity --
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maybe your personality and your intellect --
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maybe they're also encoded
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in the connections between your neurons.
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And so now you can see why I proposed this hypothesis:
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I am my connectome.
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I didn't ask you to chant it because it's true;
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I just want you to remember it.
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03:37
And in fact, we don't know if this hypothesis is correct,
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because we have never had technologies
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powerful enough to test it.
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Finding that worm connectome
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took over a dozen years of tedious labor.
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And to find the connectomes of brains more like our own,
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we need more sophisticated technologies, that are automated,
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that will speed up the process of finding connectomes.
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And in the next few minutes, I'll tell you about some of these technologies,
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which are currently under development
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in my lab and the labs of my collaborators.
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Now you've probably seen pictures of neurons before.
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You can recognize them instantly
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by their fantastic shapes.
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They extend long and delicate branches,
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and in short, they look like trees.
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But this is just a single neuron.
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In order to find connectomes,
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we have to see all the neurons at the same time.
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So let's meet Bobby Kasthuri,
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who works in the laboratory of Jeff Lichtman
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at Harvard University.
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Bobby is holding fantastically thin slices
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of a mouse brain.
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And we're zooming in by a factor of 100,000 times
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to obtain the resolution,
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so that we can see the branches of neurons all at the same time.
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Except, you still may not really recognize them,
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and that's because we have to work in three dimensions.
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If we take many images of many slices of the brain
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and stack them up,
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we get a three-dimensional image.
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And still, you may not see the branches.
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So we start at the top,
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and we color in the cross-section of one branch in red,
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and we do that for the next slice
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and for the next slice.
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And we keep on doing that,
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slice after slice.
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If we continue through the entire stack,
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we can reconstruct the three-dimensional shape
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of a small fragment of a branch of a neuron.
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And we can do that for another neuron in green.
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And you can see that the green neuron touches the red neuron
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at two locations,
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and these are what are called synapses.
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Let's zoom in on one synapse,
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and keep your eyes on the interior of the green neuron.
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You should see small circles --
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these are called vesicles.
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They contain a molecule know as a neurotransmitter.
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And so when the green neuron wants to communicate,
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it wants to send a message to the red neuron,
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it spits out neurotransmitter.
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At the synapse, the two neurons
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are said to be connected
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like two friends talking on the telephone.
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So you see how to find a synapse.
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How can we find an entire connectome?
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Well, we take this three-dimensional stack of images
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and treat it as a gigantic three-dimensional coloring book.
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We color every neuron in, in a different color,
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and then we look through all of the images,
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find the synapses
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and note the colors of the two neurons involved in each synapse.
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If we can do that throughout all the images,
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we could find a connectome.
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Now, at this point,
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you've learned the basics of neurons and synapses.
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And so I think we're ready to tackle
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one of the most important questions in neuroscience:
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how are the brains of men and women different?
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06:42
(Laughter)
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According to this self-help book,
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guys brains are like waffles;
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they keep their lives compartmentalized in boxes.
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Girls' brains are like spaghetti;
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everything in their life is connected to everything else.
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(Laughter)
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You guys are laughing,
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but you know, this book changed my life.
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(Laughter)
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But seriously, what's wrong with this?
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You already know enough to tell me -- what's wrong with this statement?
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It doesn't matter whether you're a guy or girl,
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everyone's brains are like spaghetti.
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Or maybe really, really fine capellini with branches.
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Just as one strand of spaghetti
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contacts many other strands on your plate,
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one neuron touches many other neurons
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through their entangled branches.
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One neuron can be connected to so many other neurons,
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because there can be synapses
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at these points of contact.
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By now, you might have sort of lost perspective
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on how large this cube of brain tissue actually is.
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And so let's do a series of comparisons to show you.
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I assure you, this is very tiny. It's just six microns on a side.
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So, here's how it stacks up against an entire neuron.
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And you can tell that, really, only the smallest fragments of branches
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are contained inside this cube.
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And a neuron, well, that's smaller than brain.
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And that's just a mouse brain --
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it's a lot smaller than a human brain.
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So when show my friends this,
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sometimes they've told me,
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"You know, Sebastian, you should just give up.
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Neuroscience is hopeless."
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Because if you look at a brain with your naked eye,
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you don't really see how complex it is,
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but when you use a microscope,
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finally the hidden complexity is revealed.
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In the 17th century,
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the mathematician and philosopher, Blaise Pascal,
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wrote of his dread of the infinite,
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his feeling of insignificance
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at contemplating the vast reaches of outer space.
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And, as a scientist,
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I'm not supposed to talk about my feelings --
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too much information, professor.
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(Laughter)
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But may I?
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(Laughter)
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(Applause)
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I feel curiosity,
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and I feel wonder,
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but at times I have also felt despair.
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Why did I choose to study
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this organ that is so awesome in its complexity
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that it might well be infinite?
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It's absurd.
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How could we even dare to think
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that we might ever understand this?
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And yet, I persist in this quixotic endeavor.
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And indeed, these days I harbor new hopes.
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Someday,
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a fleet of microscopes will capture
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every neuron and every synapse
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in a vast database of images.
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And some day, artificially intelligent supercomputers
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will analyze the images without human assistance
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to summarize them in a connectome.
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I do not know, but I hope that I will live to see that day,
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because finding an entire human connectome
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is one of the greatest technological challenges of all time.
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It will take the work of generations to succeed.
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At the present time, my collaborators and I,
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what we're aiming for is much more modest --
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just to find partial connectomes
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of tiny chunks of mouse and human brain.
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But even that will be enough for the first tests of this hypothesis
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that I am my connectome.
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For now, let me try to convince you of the plausibility of this hypothesis,
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that it's actually worth taking seriously.
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As you grow during childhood
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and age during adulthood,
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your personal identity changes slowly.
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Likewise, every connectome
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changes over time.
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What kinds of changes happen?
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Well, neurons, like trees,
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can grow new branches,
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and they can lose old ones.
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Synapses can be created,
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and they can be eliminated.
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And synapses can grow larger,
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and they can grow smaller.
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Second question:
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what causes these changes?
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Well, it's true.
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To some extent, they are programmed by your genes.
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But that's not the whole story,
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because there are signals, electrical signals,
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that travel along the branches of neurons
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and chemical signals
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that jump across from branch to branch.
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These signals are called neural activity.
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And there's a lot of evidence
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that neural activity
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is encoding our thoughts, feelings and perceptions,
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our mental experiences.
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And there's a lot of evidence that neural activity
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can cause your connections to change.
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And if you put those two facts together,
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it means that your experiences
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can change your connectome.
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And that's why every connectome is unique,
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even those of genetically identical twins.
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The connectome is where nature meets nurture.
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And it might true
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that just the mere act of thinking
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can change your connectome --
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an idea that you may find empowering.
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What's in this picture?
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A cool and refreshing stream of water, you say.
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What else is in this picture?
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Do not forget that groove in the Earth
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called the stream bed.
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Without it, the water would not know in which direction to flow.
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And with the stream,
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I would like to propose a metaphor
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for the relationship between neural activity
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and connectivity.
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Neural activity is constantly changing.
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It's like the water of the stream; it never sits still.
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The connections
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of the brain's neural network
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determines the pathways
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along which neural activity flows.
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And so the connectome is like bed of the stream;
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but the metaphor is richer than that,
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because it's true that the stream bed
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guides the flow of the water,
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but over long timescales,
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the water also reshapes the bed of the stream.
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And as I told you just now,
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neural activity can change the connectome.
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And if you'll allow me to ascend
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to metaphorical heights,
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I will remind you that neural activity
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is the physical basis -- or so neuroscientists think --
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of thoughts, feelings and perceptions.
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And so we might even speak of
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the stream of consciousness.
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Neural activity is its water,
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and the connectome is its bed.
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So let's return from the heights of metaphor
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and return to science.
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Suppose our technologies for finding connectomes
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actually work.
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How will we go about testing the hypothesis
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"I am my connectome?"
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Well, I propose a direct test.
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Let us attempt
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to read out memories from connectomes.
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Consider the memory
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of long temporal sequences of movements,
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like a pianist playing a Beethoven sonata.
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According to a theory that dates back to the 19th century,
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such memories are stored
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as chains of synaptic connections inside your brain.
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Because, if the first neurons in the chain are activated,
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through their synapses they send messages to the second neurons, which are activated,
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and so on down the line,
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like a chain of falling dominoes.
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And this sequence of neural activation
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is hypothesized to be the neural basis
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of those sequence of movements.
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So one way of trying to test the theory
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is to look for such chains
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inside connectomes.
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But it won't be easy, because they're not going to look like this.
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They're going to be scrambled up.
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So we'll have to use our computers
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to try to unscramble the chain.
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And if we can do that,
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the sequence of the neurons we recover from that unscrambling
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will be a prediction of the pattern of neural activity
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that is replayed in the brain during memory recall.
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And if that were successful,
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that would be the first example of reading a memory from a connectome.
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(Laughter)
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What a mess --
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have you ever tried to wire up a system
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as complex as this?
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I hope not.
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But if you have, you know it's very easy to make a mistake.
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The branches of neurons are like the wires of the brain.
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Can anyone guess: what's the total length of wires in your brain?
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I'll give you a hint. It's a big number.
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(Laughter)
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I estimate, millions of miles,
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all packed in your skull.
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And if you appreciate that number,
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you can easily see
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there is huge potential for mis-wiring of the brain.
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And indeed, the popular press loves headlines like,
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"Anorexic brains are wired differently,"
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or "Autistic brains are wired differently."
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These are plausible claims,
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but in truth,
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we can't see the brain's wiring clearly enough
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to tell if these are really true.
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And so the technologies for seeing connectomes
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will allow us to finally
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read mis-wiring of the brain,
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to see mental disorders in connectomes.
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Sometimes the best way to test a hypothesis
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is to consider its most extreme implication.
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Philosophers know this game very well.
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If you believe that I am my connectome,
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I think you must also accept the idea
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that death is the destruction
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of your connectome.
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I mention this because there are prophets today
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who claim that technology
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will fundamentally alter the human condition
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and perhaps even transform the human species.
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One of their most cherished dreams
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is to cheat death
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by that practice known as cryonics.
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If you pay 100,000 dollars,
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you can arrange to have your body frozen after death
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and stored in liquid nitrogen
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in one of these tanks in an Arizona warehouse,
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awaiting a future civilization
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that is advanced to resurrect you.
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Should we ridicule the modern seekers of immortality,
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calling them fools?
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Or will they someday chuckle
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over our graves?
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I don't know --
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I prefer to test their beliefs, scientifically.
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I propose that we attempt to find a connectome
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of a frozen brain.
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We know that damage to the brain
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occurs after death and during freezing.
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The question is: has that damage erased the connectome?
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If it has, there is no way that any future civilization
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will be able to recover the memories of these frozen brains.
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Resurrection might succeed for the body,
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but not for the mind.
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On the other hand, if the connectome is still intact,
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we cannot ridicule the claims of cryonics so easily.
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I've described a quest
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that begins in the world of the very small,
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and propels us to the world of the far future.
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Connectomes will mark a turning point in human history.
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As we evolved from our ape-like ancestors
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on the African savanna,
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what distinguished us was our larger brains.
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We have used our brains to fashion
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ever more amazing technologies.
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Eventually, these technologies will become so powerful
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that we will use them to know ourselves
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by deconstructing and reconstructing
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our own brains.
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I believe that this voyage of self-discovery
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is not just for scientists,
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but for all of us.
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And I'm grateful for the opportunity to share this voyage with you today.
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Thank you.
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(Applause)
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