Allan Jones: A map of the brain

164,945 views ใƒป 2011-11-10

TED


ืื ื ืœื—ืฅ ืคืขืžื™ื™ื ืขืœ ื”ื›ืชื•ื‘ื™ื•ืช ื‘ืื ื’ืœื™ืช ืœืžื˜ื” ื›ื“ื™ ืœื”ืคืขื™ืœ ืืช ื”ืกืจื˜ื•ืŸ.

ืžืชืจื’ื: Yubal Masalker ืžื‘ืงืจ: Sigal Tifferet
00:15
Humans have long held a fascination
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ืžื–ื” ื–ืžืŸ ืจื‘ ื‘ื ื™-ืื“ื
00:17
for the human brain.
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ืžื•ืงืกืžื™ื ืžื”ืžื•ื—.
00:19
We chart it, we've described it,
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ืขืฉื™ื ื• ืชืจืฉื™ืžื™ื ืฉืœื•, ืชืืจื ื• ืื•ืชื•,
00:22
we've drawn it,
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ืฆื™ื™ืจื ื• ืื•ืชื•,
00:24
we've mapped it.
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ืžื™ืคื™ื ื• ืื•ืชื•.
00:27
Now just like the physical maps of our world
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ืื‘ืœ ื‘ื“ื™ื•ืง ื›ืžื• ืžืคื•ืช ื”ืขื•ืœื
00:30
that have been highly influenced by technology --
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ืฉื”ื•ืฉืคืขื• ืจื‘ื•ืช ืžื”ื˜ื›ื ื•ืœื•ื’ื™ื” --
00:33
think Google Maps,
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ืœื“ื•ื’ืžื ืžืคื•ืช ื’ื•ื’ืœ,
00:35
think GPS --
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ืื• GPS --
00:37
the same thing is happening for brain mapping
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ืื•ืชื• ื”ื“ื‘ืจ ืงื•ืจื” ื”ื™ื•ื ืขื ืžื™ืคื•ื™ ืžื•ื—
00:39
through transformation.
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ื‘ื’ืœืœ ื”ืฉื™ื ื•ื™ื™ื ื”ืจื‘ื™ื.
00:41
So let's take a look at the brain.
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ื”ื‘ื” ื ืขื™ืฃ ืžื‘ื˜ ืขืœ ื”ืžื•ื—.
00:43
Most people, when they first look at a fresh human brain,
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ืจื•ื‘ ื”ืื ืฉื™ื, ื›ืืฉืจ ืจื•ืื™ื ืœืจืืฉื•ื ื” ืžื•ื— ืื“ื ื˜ืจื™,
00:46
they say, "It doesn't look what you're typically looking at
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ื”ื ืื•ืžืจื™ื, "ื”ื•ื ืœื ื ืจืื” ื›ืžื• ืžื” ืฉื‘ื“ืจืš-ื›ืœืœ ืจื•ืื™ื
00:49
when someone shows you a brain."
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ื›ืืฉืจ ืžื™ืฉื”ื• ืžืจืื” ืœืš ืžื•ื—."
00:51
Typically, what you're looking at is a fixed brain. It's gray.
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ื‘ื“ืจืš-ื›ืœืœ, ืžื” ืฉืจื•ืื™ื ื–ื” ืžื•ื— ืฉืขื‘ืจ ื˜ื™ืคื•ืœ. ื”ื•ื ืืคื•ืจ.
00:54
And this outer layer, this is the vasculature,
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ืฉื™ื›ื‘ื” ื—ื™ืฆื•ื ื™ืช ื–ื•, ื–ื•ื”ื™ ืžืขืจื›ืช ื›ืœื™-ื“ื,
00:56
which is incredible, around a human brain.
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ืฉื”ื™ื ืžื“ื”ื™ืžื”, ืกื‘ื™ื‘ ื”ืžื•ื— ื”ืื ื•ืฉื™.
00:58
This is the blood vessels.
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ืืœื” ื”ื ื›ืœื™-ื”ื“ื.
01:00
20 percent of the oxygen
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20 ืื—ื•ื– ืžื”ื—ืžืฆืŸ
01:03
coming from your lungs,
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ืฉืžื’ื™ืข ืžื”ืจื™ืื•ืช,
01:05
20 percent of the blood pumped from your heart,
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20 ืื—ื•ื– ืžื”ื“ื ืฉื ืฉืื‘ ืžื”ืœื‘,
01:07
is servicing this one organ.
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ืžืฉืจืชื™ื ืื™ื‘ืจ ื™ื—ื™ื“ ื–ื”.
01:09
That's basically, if you hold two fists together,
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ื‘ื’ื“ื•ืœ, ืื ืžื—ื–ื™ืงื™ื ืฉื ื™ ืื’ืจื•ืคื™ื ืฆืžื•ื“ื™ื,
01:11
it's just slightly larger than the two fists.
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ื”ื•ื ืงืฆืช ื™ื•ืชืจ ื’ื“ื•ืœ ืžื”ื.
01:13
Scientists, sort of at the end of the 20th century,
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ืžื“ืขื ื™ื, ื‘ืกื‘ื™ื‘ื•ืช ืกื•ืฃ ื”ืžืื” ื”-20,
01:16
learned that they could track blood flow
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ืœืžื“ื• ืฉื”ื ื™ื›ื•ืœื™ื ืœืขืงื•ื‘
01:18
to map non-invasively
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ืื—ืจ ื–ืจื ื“ื ื›ื“ื™ ืœืžืคื•ืช ื‘ืฆื•ืจื” ืœื-ืคื•ืœืฉื ื™ืช,
01:21
where activity was going on in the human brain.
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ืžืงื•ืžื•ืช ื‘ื”ื ื™ืฉ ืคืขื™ืœื•ืช ื‘ืžื•ื— ื”ืื“ื.
01:24
So for example, they can see in the back part of the brain,
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ืœื“ื•ื’ืžื, ื”ื ื™ื›ื•ืœื™ื ืœื”ืกืชื›ืœ ื‘ื—ืœืง ื”ืื—ื•ืจื™ ืฉืœ ื”ืžื•ื—,
01:27
which is just turning around there.
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ืฉื‘ื“ื™ื•ืง ืคื•ื ื™ื ืœืฉื.
01:29
There's the cerebellum; that's keeping you upright right now.
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ื™ืฉ ืืช ื”ืžื•ื— ื”ืงื˜ืŸ; ืฉืžื—ื–ื™ืง ืื•ืชื ื• ื–ืงื•ืคื™ื ืžืžืฉ ืขื›ืฉื™ื•.
01:31
It's keeping me standing. It's involved in coordinated movement.
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ื”ื•ื ืžื—ื–ื™ืง ืื•ืชื™ ืขื•ืžื“. ื”ื•ื ืงืฉื•ืจ ื‘ืชื ื•ืขื” ืžืชื•ืืžืช.
01:34
On the side here, this is temporal cortex.
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ื›ืืŸ ื‘ืฆื“, ื–ื•ื”ื™ ืื•ื ื” ืจืงืชื™ืช.
01:37
This is the area where primary auditory processing --
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ื–ื”ื• ื”ืžืงื•ื ื‘ื• ืžืชืจื—ืฉ ืขื™ื‘ื•ื“ ื”ืฉืžื™ืขื” ื”ืจืืฉื•ื ื™ --
01:40
so you're hearing my words,
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ื›ืš ืืชื ืฉื•ืžืขื™ื ืืช ืžื™ืœื•ืชื™ื™,
01:42
you're sending it up into higher language processing centers.
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ืืชื ืžืฉื’ืจื™ื ืื•ืชืŸ ืืœ ืžืจื›ื–ื™ ืขื™ื‘ื•ื“ ืฉืคื” ื™ื•ืชืจ ื’ื‘ื•ื”ื™ื.
01:44
Towards the front of the brain
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ื‘ืงื™ื“ืžืช ื”ืžื•ื— ืžืชืจื—ืฉื™ื
01:46
is the place in which all of the more complex thought, decision making --
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ื”ืชื”ืœื™ื›ื™ื ื”ื™ื•ืชืจ ืžื•ืจื›ื‘ื™ื ืฉืœ ืžื—ืฉื‘ื”, ืงื‘ืœืช ื”ื—ืœื˜ื•ืช --
01:49
it's the last to mature in late adulthood.
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ืื–ื•ืจ ื–ื” ื”ื•ื ื”ืื—ืจื•ืŸ ืœื”ืชืคืชื— ื‘ืชืงื•ืคืช ื”ื‘ื’ืจื•ืช ื”ืžืื•ื—ืจืช.
01:53
This is where all your decision-making processes are going on.
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ื›ืืŸ ืžืชืจื—ืฉื™ื ื›ืœ ืชื”ืœื™ื›ื™ ืงื‘ืœืช ื”ื”ื—ืœื˜ื•ืช.
01:56
It's the place where you're deciding right now
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ื–ื” ื”ืื–ื•ืจ ื‘ื• ืืชื ืžื—ืœื™ื˜ื™ื ื‘ืจื’ืข ื–ื”
01:58
you probably aren't going to order the steak for dinner.
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ืฉืื™ื ื›ื ืžืชื›ื•ื•ื ื™ื ืœื”ื–ืžื™ืŸ ืืช ื”ืกื˜ื™ื™ืง ืœืืจื•ื—ื”.
02:01
So if you take a deeper look at the brain,
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ื›ืš ืฉืื ืžืชื‘ื•ื ื ื™ื ื™ื•ืชืจ ืขืžื•ืง ืœืชื•ืš ื”ืžื•ื—,
02:03
one of the things, if you look at it in cross-section,
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ืื ืžืกืชื›ืœื™ื ืขืœื™ื• ื‘ื—ืชืš ืจื•ื—ื‘,
02:05
what you can see
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ืžื” ืฉืžื‘ื—ื™ื ื™ื
02:07
is that you can't really see a whole lot of structure there.
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ื”ื•ื ืฉืœื ื ื™ืชืŸ ืœืจืื•ืช ืืช ื”ืžื‘ื ื” ืœืคืจื˜ื™ื•.
02:10
But there's actually a lot of structure there.
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ืื‘ืœ ืœืžืขืฉื” ื™ืฉ ื‘ื–ื” ื”ืžื•ืŸ ืคื™ืจื•ื˜.
02:12
It's cells and it's wires all wired together.
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ืืœื” ืชืื™ื ื•ื—ื™ื•ื•ื˜ื™ื ื”ืžื—ื•ื‘ืจื™ื ื–ื” ืœื–ื”.
02:14
So about a hundred years ago,
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ืœืคื ื™ ื›ืžืื” ืฉื ื”,
02:16
some scientists invented a stain that would stain cells.
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ื›ืžื” ืžื“ืขื ื™ื ื”ืžืฆื™ืื• ื—ื•ืžืจ ืฉืฆื•ื‘ืข ืชืื™ื.
02:18
And that's shown here in the the very light blue.
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ื”ื•ื ื ืจืื” ื›ืืŸ ื‘ืชื›ืœืช ื‘ื”ื™ืจื”.
02:21
You can see areas
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ื ื™ืชืŸ ืœืจืื•ืช ืื–ื•ืจื™ื
02:23
where neuronal cell bodies are being stained.
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ื‘ื”ื ืชืื™ ืขืฆื‘ ื ืฆื‘ืขื™ื.
02:25
And what you can see is it's very non-uniform. You see a lot more structure there.
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ื•ืจื•ืื™ื ืฉื–ื” ืœื ืื—ื™ื“. ื™ืฉ ื”ืจื‘ื” ืžื‘ื ื™ื.
02:28
So the outer part of that brain
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ื›ืš ืฉื”ื—ืœืง ื”ื—ื™ืฆื•ื ื™ ืฉืœ ื”ืžื•ื—
02:30
is the neocortex.
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ื”ื•ื ื”ื ื™ืื•-ืงื•ืจื˜ืงืก.
02:32
It's one continuous processing unit, if you will.
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ืื ืชืจืฆื•, ื–ื•ื”ื™ ื™ื—ื™ื“ืช ืขื™ื‘ื•ื“ ืื—ืช ืจืฆื•ืคื”.
02:35
But you can also see things underneath there as well.
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ืื‘ืœ ื ื™ืชืŸ ื’ื ืœืจืื•ืช ื“ื‘ืจื™ื ืžืชื—ืช.
02:37
And all of these blank areas
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ื•ื›ืœ ื”ืื–ื•ืจื™ื ื”ืจื™ืงื™ื ื”ืœืœื•
02:39
are the areas in which the wires are running through.
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ื”ื ื”ืื–ื•ืจื™ื ื‘ื”ื ืขื•ื‘ืจื™ื ื”ืกื™ื‘ื™ื.
02:41
They're probably less cell dense.
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ื›ื›ืœ ื”ื ืจืื” ื”ื ืคื—ื•ืช ืฆืคื•ืคื™ื ื‘ืชืื™ื.
02:43
So there's about 86 billion neurons in our brain.
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ื™ืฉื ื ื›-86 ืžื™ืœื™ืืจื“ ืชืื™-ืขืฆื‘ ื‘ืžื•ื— ืฉืœื ื•.
02:47
And as you can see, they're very non-uniformly distributed.
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ื•ื›ืคื™ ืฉืจื•ืื™ื, ื”ื ืื™ื ื ืžืคื•ื–ืจื™ื ื‘ืื•ืคืŸ ืื—ื™ื“.
02:50
And how they're distributed really contributes
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ืื•ืคืŸ ืคื™ื–ื•ืจื ืงื•ื‘ืข ืžื”ื•ืชื™ืช
02:52
to their underlying function.
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ืืช ืฆื•ืจืช ืคืขื•ืœืชื.
02:54
And of course, as I mentioned before,
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ื•ื›ืคื™ ืฉื”ื–ื›ืจืชื™ ืงื•ื“ื,
02:56
since we can now start to map brain function,
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ืžืื—ืจ ื•ืื ื• ื™ื›ื•ืœื™ื ืขืชื” ืœื”ืชื—ื™ืœ ืœืžืคื•ืช ืืช ืคืขื™ืœื•ืช ื”ืžื•ื—,
02:59
we can start to tie these into the individual cells.
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ื ื•ื›ืœ ืœื”ืชื—ื™ืœ ื•ืœืงืฉื•ืจ ืื•ืชื ืœืชืื™ื ืžื•ื’ื“ืจื™ื.
03:02
So let's take a deeper look.
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ื”ื‘ื” ื ืชื‘ื•ื ืŸ ื™ื•ืชืจ ืขืžื•ืง.
03:04
Let's look at neurons.
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ื ืชื‘ื•ื ืŸ ื‘ืชืื™-ืขืฆื‘.
03:06
So as I mentioned, there are 86 billion neurons.
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ื›ืคื™ ืฉืืžืจืชื™, ื™ืฉื ื 86 ืžื™ืœื™ืืจื“ ืชืื™-ืขืฆื‘.
03:08
There are also these smaller cells as you'll see.
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ื™ืฉ ื’ื ืชืื™ื ื™ื•ืชืจ ืงื˜ื ื™ื ื›ืคื™ ืฉืจื•ืื™ื.
03:10
These are support cells -- astrocytes glia.
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ืืœื” ื›ื•ืœื ืชืื™ื ืชื•ืžื›ื™ื -- ืืกื˜ืจื•ืฆื™ื˜ื™ื, ืชืื™ ื’ืœื™ื™ื”.
03:12
And the nerves themselves
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ื”ืขืฆื‘ื™ื ืขืฆืžื,
03:15
are the ones who are receiving input.
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ื”ื ืืœื” ืฉืžืงื‘ืœื™ื ืืช ื”ืงืœื˜.
03:17
They're storing it, they're processing it.
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ื”ื ืžืื—ืกื ื™ื ืื•ืชื•, ื”ื ืžืขื‘ื“ื™ื ืื•ืชื•.
03:19
Each neuron is connected via synapses
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ื›ืœ ืขืฆื‘ ืžื—ื•ื‘ืจ ื‘ืืžืฆืขื•ืช ืกื™ื ืคืกื”
03:23
to up to 10,000 other neurons in your brain.
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ืœืขื“ 10,000 ืชืื™-ืขืฆื‘ ืื—ืจื™ื ื‘ืžื•ื— ืฉืœื ื•.
03:26
And each neuron itself
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ื›ืœ ืชื-ืขืฆื‘
03:28
is largely unique.
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ื”ื•ื ืžืื•ื“ ื™ื™ื—ื•ื“ื™.
03:30
The unique character of both individual neurons
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ื”ืื•ืคื™ ื”ื™ื™ื—ื•ื“ื™, ื”ืŸ ืฉืœ ืชืื™-ื”ืขืฆื‘ ื”ื‘ื•ื“ื“ื™ื
03:32
and neurons within a collection of the brain
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ื•ื”ืŸ ืฉืœ ืชืื™-ื”ืขืฆื‘ ื‘ืชื•ืš ืื™ื–ื•ืจ ื‘ืžื•ื—,
03:34
are driven by fundamental properties
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ื ืงื‘ืข ืขืœ-ื™ื“ื™ ืžืืคื™ื™ื ื™ื
03:37
of their underlying biochemistry.
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ื‘ื™ื•ื›ื™ืžื™ื™ื ื‘ืกื™ืกื™ื™ื.
03:39
These are proteins.
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ืืœื” ื”ื ื—ืœื‘ื•ื ื™ื.
03:41
They're proteins that are controlling things like ion channel movement.
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ื—ืœื‘ื•ื ื™ื ื”ืžื•ื•ืกืชื™ื ื“ื‘ืจื™ื ื›ืžื• ืชื ื•ืขืช ืชืขืœื•ืช ื™ื•ื ื™ื.
03:44
They're controlling who nervous system cells partner up with.
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ื”ื ืฉื•ืœื˜ื™ื ืขืœ ื”ืงืฉืจื™ื ืฉื™ื•ืฆืจื™ื ืชืื™ ืžืขืจื›ืช ืขืฆื‘ื™ื.
03:48
And they're controlling
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ื‘ืขื™ืงืจื•ืŸ ื”ื ืฉื•ืœื˜ื™ื ืขืœ ื›ืœ ื“ื‘ืจ
03:50
basically everything that the nervous system has to do.
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ื”ืงืฉื•ืจ ื‘ืžืขืจื›ืช ืขืฆื‘ื™ื.
03:52
So if we zoom in to an even deeper level,
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ืื ื ืชืžืงื“ ื‘ืจืžื” ื™ื•ืชืจ ืขืžื•ืงื”,
03:55
all of those proteins
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ื›ืœ ื”ื—ืœื‘ื•ื ื™ื ื”ืืœื”
03:57
are encoded by our genomes.
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ืžืงื•ื“ื“ื™ื ืขืœ-ื™ื“ื™ ื”ื’ื ื•ืžื™ื ืฉืœื ื•.
03:59
We each have 23 pairs of chromosomes.
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ืœื›ืœ ืื—ื“ ืžืื™ืชื ื• ื™ืฉ 23 ื–ื•ื’ื•ืช ืฉืœ ื›ืจื•ืžื•ื–ื•ืžื™ื.
04:02
We get one from mom, one from dad.
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ืื—ื“ ืžืงื‘ืœื™ื ืžืืžื ื•ืื—ื“ ืžืื‘ื.
04:04
And on these chromosomes
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ื•ื‘ื›ืจื•ืžื•ื–ื•ืžื™ื ืืœื”
04:06
are roughly 25,000 genes.
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ื™ืฉ ื‘ืขืจืš 25,000 ื’ื ื™ื.
04:08
They're encoded in the DNA.
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ื”ื ืžืงื•ื“ื“ื™ื ื‘-DNA.
04:10
And the nature of a given cell
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ื•ื”ืื•ืคื™ ืฉืœ ื›ืœ ืชื,
04:13
driving its underlying biochemistry
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ืฉืงื•ื‘ืข ืืช ื”ื‘ื™ื•ื›ื™ืžื™ื” ืฉืœื•,
04:15
is dictated by which of these 25,000 genes
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ืžื•ื›ืชื‘ ืขืœ-ื™ื“ื™ ืื™ืœื• ื’ื ื™ื ืžืชื•ืš ื”-25,000
04:18
are turned on
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ื™ื•ืคืขืœื•
04:20
and at what level they're turned on.
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ื•ื‘ืื™ื–ื• ืจืžื” ื”ื ื™ื•ืคืขืœื•.
04:22
And so our project
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ื”ืžื™ื–ื ืฉืœื ื•
04:24
is seeking to look at this readout,
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ืฉื•ืืฃ ืœื”ืชื‘ื•ื ืŸ ื‘ืคืœื˜ ื”ื–ื”,
04:27
understanding which of these 25,000 genes is turned on.
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ื•ืœื”ื‘ื™ืŸ ืื™ื–ื” ืžื‘ื™ืŸ 25,000 ื”ื’ื ื™ื ื”ืœืœื• ืžื•ืคืขืœื™ื.
04:30
So in order to undertake such a project,
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ืœื›ืŸ ืžื•ื‘ืŸ ืžืืœื™ื• ืฉื›ื“ื™ ืœื‘ืฆืข ืžื™ื–ื ื›ื–ื”,
04:33
we obviously need brains.
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ืื ื• ื–ืงื•ืงื™ื ืœืžื•ื—ื•ืช.
04:36
So we sent our lab technician out.
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ืœื›ืŸ ืฉืœื—ื ื• ืืช ื˜ื›ื ืื™ ื”ืžืขื‘ื“ื” ืœื—ืคืฉ.
04:39
We were seeking normal human brains.
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ื—ื™ืคืฉื ื• ืžื•ื—ื•ืช ืื“ื ืจื’ื™ืœื™ื.
04:41
What we actually start with
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ื”ืชื—ืœื ื• ืืฆืœ
04:43
is a medical examiner's office.
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ืคืชื•ืœื•ื’.
04:45
This a place where the dead are brought in.
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ื–ื” ื”ืžืงื•ื ืืœื™ื• ืžื•ื‘ืื™ื ื”ืžืชื™ื.
04:47
We are seeking normal human brains.
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ืื ื• ืžื—ืคืฉื™ื ืžื•ื—ื•ืช ืื“ื ืจื’ื™ืœื™ื.
04:49
There's a lot of criteria by which we're selecting these brains.
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ื™ืฉ ื”ืจื‘ื” ืงืจื™ื˜ืจื™ื•ื ื™ื ืœืคื™ื”ื ืื ื• ื‘ื•ื—ืจื™ื ืžื•ื—ื•ืช ืืœื”.
04:52
We want to make sure
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ื‘ืจืฆื•ื ื ื• ืœื•ื•ื“ื
04:54
that we have normal humans between the ages of 20 to 60,
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ืฉื™ืฉ ื‘ื™ื“ื™ื ื• ืื ืฉื™ื ืจื’ื™ืœื™ื ื‘ื’ื™ืœืื™ื 20 ืขื“ 60,
04:57
they died a somewhat natural death
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ืฉื”ื ื ืคื˜ืจื• ื‘ืžื•ื•ืช ื˜ื‘ืขื™
04:59
with no injury to the brain,
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ืœืœื ืคื’ื™ืขื” ืžื•ื—ื™ืช,
05:01
no history of psychiatric disease,
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ืฉืื™ืŸ ืœื”ื ื”ื™ืกื˜ื•ืจื™ื” ืฉืœ ืžื—ืœืช ื ืคืฉ,
05:03
no drugs on board --
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ืฉืœื ื”ื™ื” ืฉื™ืžื•ืฉ ื‘ืกืžื™ื --
05:05
we do a toxicology workup.
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ืื ื• ืขื•ืฉื™ื ื‘ื“ื™ืงื•ืช ืจืขืœื™ื.
05:07
And we're very careful
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ืื ื• ืžืื•ื“ ื ื–ื”ืจื™ื ื‘ื ื•ื’ืข
05:09
about the brains that we do take.
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ืœืžื•ื—ื•ืช ืฉืื ื• ื‘ื•ื—ืจื™ื.
05:11
We're also selecting for brains
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ื›ืžื•-ื›ืŸ ืื ื• ื‘ื•ื—ืจื™ื ืžื•ื—ื•ืช
05:13
in which we can get the tissue,
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ืฉื ื™ืชืŸ ืœื™ื˜ื•ืœ ืžื”ื ืจื™ืงืžื”,
05:15
we can get consent to take the tissue
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ืฉืื ื• ื™ื›ื•ืœื™ื ืœืงื‘ืœ ื”ืกื›ืžื” ืœื ื˜ื™ืœืช ื”ืจื™ืงืžื”
05:17
within 24 hours of time of death.
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ื‘ืชื•ืš 24 ืฉืขื•ืช ืžืฉืขืช ื”ืคื˜ื™ืจื”.
05:19
Because what we're trying to measure, the RNA --
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ืžื›ื™ื•ื•ืŸ ืฉื”ื“ื‘ืจ ืฉืื ื• ืžื ืกื™ื ืœืžื“ื•ื“, ื”-RNA --
05:22
which is the readout from our genes --
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ืฉื”ื•ื ื”ืคืœื˜ ืžื˜ืขื ื”ื’ื ื™ื --
05:24
is very labile,
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ื”ื•ื ืžืื•ื“ ืœื ื™ืฆื™ื‘,
05:26
and so we have to move very quickly.
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ื•ืœื›ืŸ ืขืœื™ื ื• ืœืคืขื•ืœ ื‘ืžื”ื™ืจื•ืช ืจื‘ื”.
05:28
One side note on the collection of brains:
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ื”ืขืจืช ืฉื•ืœื™ื™ื ืขืœ ืื™ืกื•ืฃ ืžื•ื—ื•ืช:
05:31
because of the way that we collect,
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ื‘ื’ืœืœ ื”ื“ืจืš ื‘ื” ืื ื• ืื•ืกืคื™ื,
05:33
and because we require consent,
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ื•ืžืฉื•ื ืฉืื ื• ื–ืงื•ืงื™ื ืœื”ืกื›ืžื”,
05:35
we actually have a lot more male brains than female brains.
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ื™ืฉ ืœื ื• ื”ืจื‘ื” ื™ื•ืชืจ ืžื•ื—ื•ืช ืฉืœ ื’ื‘ืจื™ื ืžืืฉืจ ื ืฉื™ื.
05:38
Males are much more likely to die an accidental death in the prime of their life.
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ืœื’ื‘ืจื™ื ื™ืฉ ืกื‘ื™ืจื•ืช ื”ืจื‘ื” ื™ื•ืชืจ ื’ื‘ื•ื”ื” ืœืžื•ืช ื‘ืื•ืคืŸ ืœื ืฆืคื•ื™ ื‘ืฉืœื‘ ืžื•ืงื“ื ืฉืœ ื—ื™ื™ื”ื.
05:41
And men are much more likely
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ื•ืœื’ื‘ืจื™ื ื™ืฉ ืกื‘ื™ืจื•ืช ื™ื•ืชืจ ื’ื‘ื•ื”ื”
05:43
to have their significant other, spouse, give consent
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ืฉื‘ืช-ื–ื•ื’ื ืชืชืŸ ืืช ื”ืกื›ืžืชื”
05:46
than the other way around.
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ืžืืฉืจ ื”ืžืฆื‘ ื”ื”ืคื•ืš.
05:48
(Laughter)
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(ืฆื—ื•ืง)
05:52
So the first thing that we do at the site of collection
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ืœื›ืŸ ื”ื“ื‘ืจ ื”ืจืืฉื•ืŸ ืฉืื ื• ืขื•ืฉื™ื ื‘ืืชืจ ื”ืื™ืกื•ืฃ
05:54
is we collect what's called an MR.
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ื–ื” ืœื™ื˜ื•ืœ ืืช ืžื” ืฉื ืงืจื MR.
05:56
This is magnetic resonance imaging -- MRI.
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ื–ื•ื”ื™ ื”ื“ืžื™ื” ื‘ืชื”ื•ื“ื” ืžื’ื ื˜ื™ืช -- MRI.
05:58
It's a standard template by which we're going to hang the rest of this data.
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ื–ื•ื”ื™ ืชื‘ื ื™ืช ืกื˜ื ื“ืจื˜ื™ืช ืฉื‘ืืžืฆืขื•ืชื” ื ืฆื™ื’ ืืช ื›ืœ ื”ื ืชื•ื ื™ื.
06:01
So we collect this MR.
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ืื ื• ืื•ืกืคื™ื ืืช ื”-MR.
06:03
And you can think of this as our satellite view for our map.
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ืžืขื™ืŸ ืžื‘ื˜-ืขืœ ืœืฆื•ืจืš ื”ืžืคื” ืฉืœื ื•.
06:05
The next thing we do
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ื”ื“ื‘ืจ ื”ื‘ื ืฉืื ื• ืขื•ืฉื™ื
06:07
is we collect what's called a diffusion tensor imaging.
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ื–ื• ื”ื“ืžื™ื™ืช DTI.
06:10
This maps the large cabling in the brain.
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ื”ื™ื ืžืžืคื” ืืช ื”ื›ื‘ืœื™ื ื”ื’ื“ื•ืœื™ื ื‘ืžื•ื—.
06:12
And again, you can think of this
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ืืคืฉืจ ืœื—ืฉื•ื‘ ืขืœ ื–ื” ื›ืžืขื˜
06:14
as almost mapping our interstate highways, if you will.
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ื›ืžื• ืžื™ืคื•ื™ ืฉืœ ื›ื‘ื™ืฉื™ื ืžื”ื™ืจื™ื ื‘ื™ืŸ-ืขื™ืจื•ื ื™ื™ื.
06:16
The brain is removed from the skull,
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ื”ืžื•ื— ืžื•ืกืจ ืžื”ื’ื•ืœื’ื•ืœืช,
06:18
and then it's sliced into one-centimeter slices.
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ื•ืื– ื ืคืจืก ืœืคืจื•ืกื•ืช ื‘ื ื•ืช 1 ืก"ืž.
06:21
And those are frozen solid,
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ื”ืŸ ืขื•ื‘ืจื•ืช ื”ืงืคืื”
06:23
and they're shipped to Seattle.
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ื•ื ืฉืœื—ื•ืช ืœืกื™ืื˜ืœ.
06:25
And in Seattle, we take these --
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ื‘ืกื™ืื˜ืœ ืื ื• ื ื•ื˜ืœื™ื ืื•ืชืŸ --
06:27
this is a whole human hemisphere --
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ื–ื•ื”ื™ ืื•ื ืช ืžื•ื— ืื ื•ืฉื™ืช ืฉืœืžื” --
06:29
and we put them into what's basically a glorified meat slicer.
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ื•ืื ื• ืฉืžื™ื ืื•ืชืŸ ื‘ื—ื•ืชืš ื”ื‘ืฉืจ ื”ืžื”ื•ืœืœ.
06:31
There's a blade here that's going to cut across
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ื™ืฉ ืœื”ื‘ ืฉื™ื—ืชื•ืš
06:33
a section of the tissue
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ืžืงื˜ืข ืžื”ืจื™ืงืžื”,
06:35
and transfer it to a microscope slide.
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ื•ืื– ืœื”ืขื‘ื™ืจื• ืืœ ื–ื›ื•ื›ื™ืช ื ื•ืฉืืช.
06:37
We're going to then apply one of those stains to it,
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ืœืื—ืจ-ืžื›ืŸ ืฆื•ื‘ืขื™ื ืื•ืชื•
06:39
and we scan it.
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ื•ืื– ืกื•ืจืงื™ื ืื•ืชื•.
06:41
And then what we get is our first mapping.
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ื›ืš ืžืงื‘ืœื™ื ืืช ื”ืžื™ืคื•ื™ ื”ืจืืฉื•ืŸ.
06:44
So this is where experts come in
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ื›ืืŸ ื ื›ื ืกื™ื ืœืคืขื•ืœื” ื”ืžื•ืžื—ื™ื ืฉืœื ื•
06:46
and they make basic anatomic assignments.
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ื•ื”ื ืžื‘ืฆืขื™ื ืžืฉื™ืžื•ืช ืื ื˜ื•ืžื™ื•ืช ืคืฉื•ื˜ื•ืช.
06:48
You could consider this state boundaries, if you will,
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ืืคืฉืจ ืœื“ืžื™ื™ืŸ ืืช ืงื•ื™-ื”ืžื™ืชืืจ ื”ืขื‘ื™ื ื”ืœืœื•
06:51
those pretty broad outlines.
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ื‘ืชื•ืจ ื’ื‘ื•ืœื•ืช ื‘ื™ืŸ ืžื“ื™ื ื•ืช.
06:53
From this, we're able to then fragment that brain into further pieces,
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ืžื›ืืŸ ืื ื• ื™ื›ื•ืœื™ื ืœืคืฆืœ ืืช ืคื™ืกืช ื”ืžื•ื— ืœื—ืœืงื™ื ื™ื•ืชืจ ืงื˜ื ื™ื, ืฉืื•ืชื ืืคืฉืจ ืœื”ื ื™ื—
06:57
which then we can put on a smaller cryostat.
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ืขืœ-ื’ื‘ื™ ื”ืชืงืŸ ื”ืฉื•ืžืจ ืขืœ ื˜ืžืคืจื˜ื•ืจื” ื ืžื•ื›ื”.
06:59
And this is just showing this here --
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ื›ืืŸ ืคืฉื•ื˜ ืจื•ืื™ื ืืช ื›ืœ ื–ื” --
07:01
this frozen tissue, and it's being cut.
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ืืช ื”ืจื™ืงืžื” ื”ืงืคื•ืื”, ื›ืืฉืจ ื”ื™ื ื ื—ืชื›ืช.
07:03
This is 20 microns thin, so this is about a baby hair's width.
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ื”ืขื•ื‘ื™ ืฉืœ ื–ื” ื”ื•ื 20 ืžื™ืงืจื•ืŸ, ืฉื–ื” ื›ืžื• ืขื•ื‘ื™ ืฉื™ืขืจ ืชื™ื ื•ืง.
07:06
And remember, it's frozen.
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ื•ื™ืฉ ืœื–ื›ื•ืจ ืฉื–ื” ืงืคื•ื.
07:08
And so you can see here,
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ื›ืืŸ ื ื™ืชืŸ ืœืจืื•ืช ื˜ื›ื ื•ืœื•ื’ื™ื” ื™ืฉื ื” --
07:10
old-fashioned technology of the paintbrush being applied.
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ืฉื™ืžื•ืฉ ื‘ืžื‘ืจืฉืช ืฆื‘ืข.
07:12
We take a microscope slide.
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ืœื•ืงื—ื™ื ื–ื›ื•ื›ื™ืช ื ื•ืฉืืช
07:14
Then we very carefully melt onto the slide.
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ื•ืžืชื™ื›ื™ื ืžืชื—ืชื™ื” ื‘ื–ื”ื™ืจื•ืช.
07:17
This will then go onto a robot
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ืื—ืจ-ื›ืš ื–ื” ืžื•ืขื‘ืจ ืœืจื•ื‘ื•ื˜
07:19
that's going to apply one of those stains to it.
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ืฉื™ืฆื‘ืข ืื•ืชื• ื‘ืื—ื“ ื”ืฆื‘ืขื™ื ื”ื”ื.
07:26
And our anatomists are going to go in and take a deeper look at this.
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ื—ื•ืงืจื™ ื”ืื ื˜ื•ืžื™ื” ื™ื‘ื—ื ื• ืืช ื–ื” ื‘ืื•ืคืŸ ื™ื•ืชืจ ืžืขืžื™ืง.
07:29
So again this is what they can see under the microscope.
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ื•ื–ื” ืžื” ืฉื”ื ืจื•ืื™ื ืชื—ืช ืžื™ืงืจื•ืกืงื•ืค.
07:31
You can see collections and configurations
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ื ื™ืชืŸ ืœืจืื•ืช ืจื™ื›ื•ื–ื™ื ื•ืžื‘ื ื™ื
07:33
of large and small cells
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ืฉืœ ืชืื™ื ื’ื“ื•ืœื™ื ื•ืงื˜ื ื™ื
07:35
in clusters and various places.
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ื‘ืงื‘ื•ืฆื•ืช ื‘ืื–ื•ืจื™ื ืฉื•ื ื™ื.
07:37
And from there it's routine. They understand where to make these assignments.
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ืžื›ืืŸ ื–ื• ืขื‘ื•ื“ื” ืฉื’ืจืชื™ืช.
07:39
And they can make basically what's a reference atlas.
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ื”ื ื™ื›ื•ืœื™ื ืœื™ืฆื•ืจ ืžื™ืŸ ืื˜ืœืก ืฉื”ื•ื ืžืจืื”-ืžืงื•ื.
07:42
This is a more detailed map.
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ื–ื• ืžืคื” ื™ื•ืชืจ ืžืคื•ืจื˜ืช.
07:44
Our scientists then use this
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ื”ืžื“ืขื ื™ื ืฉืœื ื• ืžืฉืชืžืฉื™ื ื‘ื–ื”
07:46
to go back to another piece of that tissue
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ื›ื“ื™ ืœื—ื–ื•ืจ ืœืคื™ืกื” ืื—ืจืช ืžืื•ืชื” ืจื™ืงืžื” ื•ืœื‘ืฆืข
07:49
and do what's called laser scanning microdissection.
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ืืช ืžื” ืฉืงืจื•ื™ LMD.
07:51
So the technician takes the instructions.
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ื”ื˜ื›ื ืื™ื ืœื•ืงื—ื™ื ืืช ื”ื”ื•ืจืื•ืช.
07:54
They scribe along a place there.
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ื”ื ืžืกืžื ื™ื ืœืื•ืจืš ื”ืื–ื•ืจ.
07:56
And then the laser actually cuts.
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ื•ืื– ื”ืœื™ื™ื–ืจ ืžืžืฉ ื—ื•ืชืš.
07:58
You can see that blue dot there cutting. And that tissue falls off.
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ื ื™ืชืŸ ืœืจืื•ืช ืืช ื”ื ืงื•ื“ื” ื”ื›ื—ื•ืœื” ื—ื•ืชื›ืช. ื•ืื•ืชื” ืจื™ืงืžื” ื ื•ืคืœืช ืžื˜ื”.
08:01
You can see on the microscope slide here,
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ื ื™ืชืŸ ืœืจืื•ืช ื–ืืช ืขืœ ื”ื–ื›ื•ื›ื™ืช ื”ื ื•ืฉืืช,
08:03
that's what's happening in real time.
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ืฉื–ื” ืžื” ืฉืงื•ืจื” ื‘ื–ืžืŸ ืืžืช.
08:05
There's a container underneath that's collecting that tissue.
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ื™ืฉื ื• ืžื™ื›ืœ ืœืžื˜ื” ืืฉืจ ืงื•ืœื˜ ืืช ื”ืจื™ืงืžื”.
08:08
We take that tissue,
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ืื ื• ืœื•ืงื—ื™ื ืืช ื”ืจื™ืงืžื”,
08:10
we purify the RNA out of it
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ืžื–ืงืงื™ื ืžืžื ื” ืืช ื”-RNA
08:12
using some basic technology,
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ื‘ืืžืฆืขื•ืช ื˜ื›ื ื•ืœื•ื’ื™ื” ืคืฉื•ื˜ื”,
08:14
and then we put a florescent tag on it.
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ื•ืื– ืžืฆืžื™ื“ื™ื ืœื” ืชื’ ืคืœื•ืื•ืจื•ืฆื ื˜ื™.
08:16
We take that tagged material
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ืื ื• ืœื•ืงื—ื™ื ืืช ื”ื—ื•ืžืจ ื”ืžืชื•ื™ื™ื’
08:18
and we put it on to something called a microarray.
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ื•ืžื ื™ื—ื™ื ืื•ืชื• ืขืœ-ื’ื‘ื™ ืžื” ืฉื ืงืจื ืžืขืจืš-ืžื™ืงืจื•.
08:21
Now this may look like a bunch of dots to you,
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ื–ื” ืขืฉื•ื™ ืœื”ื™ืจืื•ืช ืœื›ื ื›ืื•ืกืฃ ืฉืœ ื ืงื•ื“ื•ืช,
08:23
but each one of these individual dots
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ืื‘ืœ ื›ืœ ืื—ืช ืžื”ื ืงื•ื“ื•ืช
08:25
is actually a unique piece of the human genome
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ื”ื™ื ืœืžืขืฉื” ื’ืŸ ืื ื•ืฉื™ ื™ื™ื—ื•ื“ื™
08:27
that we spotted down on glass.
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ืฉื ื™ืงื“ื ื• ืื™ืชื• ืืช ื”ื–ื›ื•ื›ื™ืช.
08:29
This has roughly 60,000 elements on it,
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ื™ืฉ ื›ืืŸ ื‘ืขืจืš 60,000 ื ืงื•ื“ื•ืช, ื•ื–ื” ืื•ืžืจ
08:32
so we repeatedly measure various genes
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ืฉืื ื• ืขื•ืฉื™ื ืžื“ื™ื“ื•ืช ื—ื•ื–ืจื•ืช ืฉืœ ื’ื ื™ื ืฉื•ื ื™ื
08:35
of the 25,000 genes in the genome.
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ืž-25,000 ื”ื’ื ื™ื ืฉื‘ื’ื ื•ื.
08:37
And when we take a sample and we hybridize it to it,
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ื›ืืฉืจ ืื ื• ื ื•ื˜ืœื™ื ื“ื•ื’ืžื™ืช ื•ืžื›ืœื™ืื™ื ืื•ืชื” ืขื ื–ื”,
08:40
we get a unique fingerprint, if you will,
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ืื ื• ืžืงื‘ืœื™ื ื˜ื‘ื™ืขืช-ืืฆื‘ืข ื™ื™ื—ื•ื“ื™ืช
08:42
quantitatively of what genes are turned on in that sample.
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ื›ืžื•ืชื™ืช ืฉืœ ืื™ืœื• ื’ื ื™ื ืžื•ืคืขืœื™ื ื‘ืื•ืชื” ื“ื•ื’ืžื™ืช.
08:45
Now we do this over and over again,
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ืื ื• ืขื•ืฉื™ื ื–ืืช ืฉื•ื‘ ื•ืฉื•ื‘,
08:47
this process for any given brain.
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ืืช ื”ืชื”ืœื™ืš ื”ื–ื” ืœื›ืœ ืžื•ื— ื ืชื•ืŸ.
08:50
We're taking over a thousand samples for each brain.
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ืื ื• ื ื•ื˜ืœื™ื ื™ื•ืชืจ ืžืืœืฃ ื“ื•ื’ืžื™ื•ืช ืžื›ืœ ืžื•ื—.
08:53
This area shown here is an area called the hippocampus.
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ืื–ื•ืจ ื–ื” ื”ืžื•ืฆื’ ื›ืืŸ ื ืงืจื ื”ื™ืคื•ืงืžืคื•ืก.
08:56
It's involved in learning and memory.
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ื”ื•ื ืงืฉื•ืจ ื‘ืœืžื™ื“ื” ื•ื–ื™ื›ืจื•ืŸ.
08:58
And it contributes to about 70 samples
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ื”ื•ื ืชื•ืจื ืœื›-70 ื“ื•ื’ืžื™ื•ืช
09:01
of those thousand samples.
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ืžืชื•ืš ืืœืฃ ื“ื•ื’ืžื™ื•ืช.
09:03
So each sample gets us about 50,000 data points
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ืœื›ืŸ ื›ืœ ื“ื•ื’ืžื™ืช ื ื•ืชื ืช ืœื ื• ื›-50,000 ื ืงื•ื“ื•ืช ืžื™ื“ืข
09:07
with repeat measurements, a thousand samples.
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ื‘ืžื“ื™ื“ื•ืช ื—ื•ื–ืจื•ืช, ืืœืฃ ื“ื•ื’ืžื™ื•ืช.
09:10
So roughly, we have 50 million data points
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ืœื›ืŸ ื™ืฉ ืœื ื• ื›- 50 ืžื™ืœื™ื•ืŸ ื ืงื•ื“ื•ืช ืžื™ื“ืข
09:12
for a given human brain.
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ืœืžื•ื— ืื ื•ืฉื™ ืื—ื“.
09:14
We've done right now
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ืขื“ ืขื›ืฉื™ื• ื”ืกืคืงื ื• ืœืืกื•ืฃ ืžื™ื“ืข
09:16
two human brains-worth of data.
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ื”ืฉื•ื•ื”-ืขืจืš ืœืฉื ื™ ืžื•ื—ื•ืช ืื ื•ืฉื™ื™ื.
09:18
We've put all of that together
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ื—ื™ื‘ืจื ื• ืืช ื”ื›ืœ ื‘ื™ื—ื“
09:20
into one thing,
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ืœื“ื‘ืจ ืื—ื“,
09:22
and I'll show you what that synthesis looks like.
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ื•ืืจืื” ืœื›ื ื›ื™ืฆื“ ื ืจืื” ืžื™ื–ื•ื’ ื–ื”.
09:24
It's basically a large data set of information
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ื‘ืขื™ืงืจื•ืŸ ื–ื” ืžืขืจืš ื’ื“ื•ืœ ืฉืœ ืžื™ื“ืข
09:27
that's all freely available to any scientist around the world.
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ื”ื–ืžื™ืŸ ื—ื™ื ื ืœื›ืœ ืžื“ืขืŸ ื‘ืขื•ืœื.
09:30
They don't even have to log in to come use this tool,
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ืื™ืŸ ืฆื•ืจืš ืืคื™ืœื• ืœื”ืชื—ื‘ืจ ื›ื“ื™ ืœื”ืฉืชืžืฉ ื‘ื›ืœื™ ื–ื”,
09:33
mine this data, find interesting things out with this.
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ืœื—ืคื•ืจ ื‘ืžื™ื“ืข, ืœืžืฆื•ื ืขื ื–ื” ื“ื‘ืจื™ื ืžืขื ื™ื™ื ื™ื.
09:37
So here's the modalities that we put together.
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ื”ื ื” ื”ืื•ืคื ื•ื™ื•ืช ืฉืื ื• ืžื—ื‘ืจื™ื.
09:40
You'll start to recognize these things from what we've collected before.
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ืชื•ื›ืœื• ืœื–ื”ื•ืช ื“ื‘ืจื™ื ืืœื” ืžืžื” ืฉืืกืคื ื• ืงื•ื“ื.
09:43
Here's the MR. It provides the framework.
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ื”ื ื” ื”-MR. ื”ื•ื ืžืกืคืง ืืช ื”ืžืกื’ืจืช.
09:45
There's an operator side on the right that allows you to turn,
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ืฉื ืžื™ืžื™ืŸ ื™ืฉ ืืช ื”ืžืžืฉืง ืœืžืคืขื™ืœ ืฉืžืืคืฉืจ ืœื”ื˜ื•ืช,
09:48
it allows you to zoom in,
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ืœื‘ืฆืข ื–ื•ื ืคื ื™ืžื”
09:50
it allows you to highlight individual structures.
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ื•ืœื”ื“ื’ื™ืฉ ืžื‘ื ื™ื ืžืกื•ื™ื™ืžื™ื.
09:53
But most importantly,
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ืื‘ืœ ื”ื›ื™ ื—ืฉื•ื‘,
09:55
we're now mapping into this anatomic framework,
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ืื ื• ืžืžืคื™ื ื”ื™ื•ื ืืช ื”ืžืขืจื›ืช ื”ืื ื˜ื•ืžื™ืช ื”ื–ืืช,
09:58
which is a common framework for people to understand where genes are turned on.
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ืฉื”ื™ื ื”ืžืขืจื›ืช ื”ืžืงื•ื‘ืœืช ื›ื“ื™ ืฉืื ืฉื™ื ื™ื‘ื™ื ื• ื”ื™ื›ืŸ ื”ื’ื ื™ื ืžื•ืคืขืœื™ื.
10:01
So the red levels
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ื”ืื–ื•ืจื™ื ื”ืื“ื•ืžื™ื ื”ื ื”ืžืงื•ื
10:03
are where a gene is turned on to a great degree.
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ื‘ื• ื”ื’ืŸ ืžื•ืคืขืœ ื‘ืจืžื” ื’ื‘ื•ื”ื”.
10:05
Green is the sort of cool areas where it's not turned on.
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ื™ืจื•ืง ื–ื” ืžื™ืŸ ืื–ื•ืจื™ื ืงืจื™ื ื‘ื”ื ื”ื•ื ืื™ื ื• ืžื•ืคืขืœ.
10:08
And each gene gives us a fingerprint.
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ื›ืœ ื’ืŸ ื ื•ืชืŸ ืœื ื• ื˜ื‘ื™ืขืช-ืืฆื‘ืข.
10:10
And remember that we've assayed all the 25,000 genes in the genome
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ื™ืฉ ืœื–ื›ื•ืจ ืฉื‘ื—ื ื• ืืช ื›ืœ 25,000 ื”ื’ื ื™ื ืฉื‘ื’ื ื•ื
10:15
and have all of that data available.
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ื•ื›ืœ ื”ืžื™ื“ืข ื”ื–ื” ื–ืžื™ืŸ.
10:19
So what can scientists learn about this data?
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ืžื” ื™ื›ื•ืœื™ื ื”ืžื“ืขื ื™ื ืœืœืžื•ื“ ืžืžื™ื“ืข ื–ื”?
10:21
We're just starting to look at this data ourselves.
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ืื ื• ื‘ืขืฆืžื ื• ืจืง ืžืชื—ื™ืœื™ื ืœื—ืงื•ืจ ืžื™ื“ืข ื–ื”.
10:24
There's some basic things that you would want to understand.
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ื™ืฉ ื›ืžื” ื“ื‘ืจื™ื ื‘ืกื™ืกื™ื™ื ืฉื”ื™ื™ื ื• ืจื•ืฆื™ื ืœื”ื‘ื™ืŸ.
10:27
Two great examples are drugs,
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ืฉืชื™ ื“ื•ื’ืžืื•ืช ืžืฆื•ื™ื™ื ื•ืช ื”ืŸ ืฉืœ ื”ืชืจื•ืคื•ืช,
10:29
Prozac and Wellbutrin.
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ืคืจื•ื–ืืง ื•ื•ืœื‘ื•ื˜ืจื™ืŸ.
10:31
These are commonly prescribed antidepressants.
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ืืœื” ืชืจื•ืคื•ืช ืฉื›ื™ื—ื•ืช ื ื’ื“ ื“ื™ื›ืื•ืŸ.
10:34
Now remember, we're assaying genes.
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ื™ืฉ ืœื–ื›ื•ืจ ืฉืื ื• ื‘ื•ื—ื ื™ื ื’ื ื™ื.
10:36
Genes send the instructions to make proteins.
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ื’ื ื™ื ืฉื•ืœื—ื™ื ืืช ื”ื”ื•ืจืื•ืช ืœื™ืฆื™ืจืช ื—ืœื‘ื•ื ื™ื.
10:39
Proteins are targets for drugs.
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ื—ืœื‘ื•ื ื™ื ื”ื ืžื˜ืจื•ืช ืฉืœ ืชืจื•ืคื•ืช.
10:41
So drugs bind to proteins
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ืชืจื•ืคื•ืช ืžืชื—ื‘ืจื•ืช ืœื—ืœื‘ื•ื ื™ื
10:43
and either turn them off, etc.
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ื•ื‘ื™ืŸ ื”ื™ืชืจ ืžืคืกื™ืงื•ืช ืืช ืคืขื™ืœื•ืชื ื•ื›ื•'.
10:45
So if you want to understand the action of drugs,
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ืœื›ืŸ ืื ืจื•ืฆื™ื ืœื”ื‘ื™ืŸ ืืช ืคืขื•ืœืช ื”ืชืจื•ืคื•ืช,
10:47
you want to understand how they're acting in the ways you want them to,
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ืฆืจื™ืš ืœื”ื‘ื™ืŸ ื›ื™ืฆื“ ื”ืŸ ืคื•ืขืœื•ืช ื‘ื“ืจื›ื™ื ืฉืื ื• ืจื•ืฆื™ื ืฉื™ืคืขืœื•,
10:50
and also in the ways you don't want them to.
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ื•ื’ื ื‘ื“ืจื›ื™ื ืฉืื™ืŸ ืื ื• ื—ืคืฆื™ื ื‘ื”ืŸ.
10:52
In the side effect profile, etc.,
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ื‘ืชื•ืคืขื•ืช ืœื•ื•ืื™ ื•ื›ื•',
10:54
you want to see where those genes are turned on.
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ืจื•ืฆื™ื ืœืจืื•ืช ื”ื™ื›ืŸ ืื•ืชื ื’ื ื™ื ืžื•ืคืขืœื™ื.
10:56
And for the first time, we can actually do that.
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ื•ืœืจืืฉื•ื ื”, ืื ื• ืžืžืฉ ื™ื›ื•ืœื™ื ืœื‘ืฆืข ื–ืืช.
10:58
We can do that in multiple individuals that we've assayed too.
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ืื ื• ื’ื ื™ื›ื•ืœื™ื ืœืขืฉื•ืช ื–ืืช ื‘ืื ืฉื™ื ืจื‘ื™ื ืฉื‘ื—ื ื•.
11:01
So now we can look throughout the brain.
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ื›ืขืช ืื ื• ื™ื›ื•ืœื™ื ืœื”ืกืชื›ืœ ืืœ ืชื•ืš ื”ืžื•ื—.
11:04
We can see this unique fingerprint.
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ืื ื• ื™ื›ื•ืœื™ื ืœืจืื•ืช ืืช ื˜ื‘ื™ืขืช-ื”ืืฆื‘ืข ื”ื™ื™ื—ื•ื“ื™ืช.
11:06
And we get confirmation.
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ื•ืื ื• ื’ื ืžืงื‘ืœื™ื ืื™ืฉื•ืจ ืœื›ืš.
11:08
We get confirmation that, indeed, the gene is turned on --
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ืื ื• ืžืงื‘ืœื™ื ืื™ืฉื•ืจ ืฉืื›ืŸ ื”ื’ืŸ ื”ื•ืคืขืœ --
11:11
for something like Prozac,
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ื‘ื’ืœืœ ืžืฉื”ื• ื›ืžื• ืคืจื•ื–ืืง,
11:13
in serotonergic structures, things that are already known be affected --
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ื‘ืžืขืจื›ื•ืช ืฉืœ ืกืจื•ื˜ื•ื ื™ืŸ, ืืคืงื˜ ืฉื›ื‘ืจ ืžื•ื›ืจ ืœื ื• --
11:16
but we also get to see the whole thing.
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ืื‘ืœ ืื ื• ื’ื ืžืฆืœื™ื—ื™ื ืœืจืื•ืช ืืช ื”ืชืžื•ื ื” ื›ื•ืœื”.
11:18
We also get to see areas that no one has ever looked at before,
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ืื ื• ื’ื ืžืฆืœื™ื—ื™ื ืœืจืื•ืช ืื–ื•ืจื™ื ืฉืืฃ ืื—ื“ ืœื ื‘ื—ืŸ ืžืขื•ืœื,
11:20
and we see these genes turned on there.
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ื•ืื ื• ื™ื›ื•ืœื™ื ืœืจืื•ืช ืืช ื”ื’ื ื™ื ื”ืืœื” ืžื•ืคืขืœื™ื ืฉื.
11:22
It's as interesting a side effect as it could be.
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ื–ื• ืชื•ืคืขืช ืœื•ื•ืื™ ืžืขื ื™ื™ื ืช.
11:25
One other thing you can do with such a thing
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ื“ื‘ืจ ื ื•ืกืฃ ืฉื ื™ืชืŸ ืœืขืฉื•ืช ืขื ื–ื”,
11:27
is you can, because it's a pattern matching exercise,
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ื‘ื’ืœืœ ืฉื–ื” ืชืจื’ื™ืœ ื‘ื”ืชืืžืช ืชื‘ื ื™ื•ืช,
11:30
because there's unique fingerprint,
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ื›ื™ ื™ืฉ ื˜ื‘ื™ืขืช-ืืฆื‘ืข ื™ื™ื—ื•ื“ื™ืช,
11:32
we can actually scan through the entire genome
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ืื ื• ื™ื›ื•ืœื™ื ืœืกืจื•ืง ืืช ื›ืœ ื”ื’ื ื•ื
11:34
and find other proteins
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ื•ืœืžืฆื•ื ื—ืœื‘ื•ื ื™ื ืื—ืจื™ื
11:36
that show a similar fingerprint.
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ื”ืžืจืื™ื ืื•ืชื” ื˜ื‘ื™ืขืช-ืืฆื‘ืข.
11:38
So if you're in drug discovery, for example,
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ื›ืš ืœื“ื•ื’ืžื ืื ืจื•ืฆื™ื ืœื’ืœื•ืช ืชืจื•ืคื•ืช ื—ื“ืฉื•ืช,
11:41
you can go through
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ื ื™ืชืŸ ืœืขื‘ื•ืจ ืขืœ ื›ืœ ื”ืจืฉื™ืžื”
11:43
an entire listing of what the genome has on offer
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ืฉืœ ืžื” ืฉื”ื’ื ื•ื ื™ื›ื•ืœ ืœืชืช
11:45
to find perhaps better drug targets and optimize.
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ื›ื“ื™ ืœืืชืจ ืื•ืœื™ ืžื˜ืจื•ืช ืขื“ื™ืคื•ืช ืขื‘ื•ืจ ื”ืชืจื•ืคื•ืช ื•ืœื”ืคื™ืง ืžื”ืŸ ืืช ื”ืžื™ืจื‘.
11:49
Most of you are probably familiar
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ืจื‘ื™ื ืžื›ื ื•ื“ืื™ ืžื›ื™ืจื™ื
11:51
with genome-wide association studies
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ืžื—ืงืจื™ ื’ื ื•ื ืžืœื GWAS ื‘ืฆื•ืจืช
11:53
in the form of people covering in the news
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ื”ืชืืžื•ืช ืžื›ืœื™ืœื•ืช ืฉืœ ื’ื ื•ื ื›ืืฉืจ ืฉื“ืจื™ ื—ื“ืฉื•ืช ืžืกืคืจื™ื
11:56
saying, "Scientists have recently discovered the gene or genes
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"ืžื“ืขื ื™ื ื’ื™ืœื• ืœืื—ืจื•ื ื” ืืช ื”ื’ืŸ ืื• ื”ื’ื ื™ื
11:59
which affect X."
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ื”ืžืฉืคื™ืขื™ื ืขืœ X".
12:01
And so these kinds of studies
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ืžื—ืงืจื™ื ืžื”ืกื•ื’ ื”ื–ื”
12:03
are routinely published by scientists
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ืžืชืคืจืกืžื™ื ื›ืฉื™ื’ืจื” ืขืœ-ื™ื“ื™ ื”ืžื“ืขื ื™ื
12:05
and they're great. They analyze large populations.
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ื•ื–ื” ื˜ื•ื‘. ื”ื ืžื ืชื—ื™ื ืื•ื›ืœื•ืกื™ื•ืช ื’ื“ื•ืœื•ืช.
12:07
They look at their entire genomes,
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ื”ื ืžืกืชื›ืœื™ื ืขืœ ื”ื’ื ื•ื ื”ืฉืœื ืฉืœื”ื,
12:09
and they try to find hot spots of activity
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ื•ืžื—ืคืฉื™ื ืื–ื•ืจื™ ืคืขื™ืœื•ืช "ื—ืžื™ื"
12:11
that are linked causally to genes.
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ื”ืงืฉื•ืจื™ื ื‘ืื•ืคืŸ ืกื™ื‘ืชื™ ืœื’ื ื™ื.
12:14
But what you get out of such an exercise
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ืื‘ืœ ืžื” ืฉืžืชืงื‘ืœ ืžืžื—ืงืจ ื›ื–ื”
12:16
is simply a list of genes.
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ื–ื• ืจืง ืจืฉื™ืžื” ืฉืœ ื’ื ื™ื.
12:18
It tells you the what, but it doesn't tell you the where.
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ื”ื™ื ืื•ืžืจืช ืœื ื• ืžื”, ืื‘ืœ ืœื ื”ื™ื›ืŸ.
12:21
And so it's very important for those researchers
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ืœื›ืŸ ื–ื” ืžืื•ื“ ื—ืฉื•ื‘ ืœื—ื•ืงืจื™ื ืืœื”
12:24
that we've created this resource.
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ืฉื™ืฆืจื ื• ืืช ื”ืžืื’ืจ ื”ื–ื”.
12:26
Now they can come in
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ื›ืขืช ื”ื ื™ื›ื•ืœื™ื ืœื‘ื•ื
12:28
and they can start to get clues about activity.
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ื•ืœื”ืชื—ื™ืœ ืœืงื‘ืœ ืจืžื–ื™ื ืœื’ื‘ื™ ืคืขื™ืœื•ืช.
12:30
They can start to look at common pathways --
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ื”ื ื™ื›ื•ืœื™ื ืœื”ืกืชื›ืœ ืขืœ ืžืกืœื•ืœื™ื ืžืฉื•ืชืคื™ื --
12:32
other things that they simply haven't been able to do before.
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ื“ื‘ืจื™ื ืฉื”ื ืคืฉื•ื˜ ืœื ื™ื›ืœื• ืœืขืฉื•ืช ืงื•ื“ื.
12:36
So I think this audience in particular
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ืื ื™ ื—ื•ืฉื‘ ืฉืงื”ืœ ื–ื” ื‘ืžื™ื•ื—ื“
12:39
can understand the importance of individuality.
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ื™ื›ื•ืœ ืœื”ื‘ื™ืŸ ืืช ื—ืฉื™ื‘ื•ืช ื”ืื™ื ื“ื™ื‘ื™ื“ื•ืืœื™ื•ืช.
12:42
And I think every human,
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ืื ื™ ืกื‘ื•ืจ ืฉืœื›ืœ ืื“ื
12:44
we all have different genetic backgrounds,
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ื™ืฉ ืจืงืข ื’ื ื˜ื™ ืฉื•ื ื”,
12:48
we all have lived separate lives.
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ื›ื•ืœื ื• ื—ื™ื™ื ื• ื—ื™ื™ื ื ืคืจื“ื™ื ื–ื” ืžื–ื”.
12:50
But the fact is
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ืื‘ืœ ื”ืขื•ื‘ื“ื” ื”ื™ื
12:52
our genomes are greater than 99 percent similar.
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ืฉื”ื’ื ื•ืžื™ื ืฉืœื ื• ื–ื”ื™ื ื‘ื™ื•ืชืจ ืž-99 ืื—ื•ื–.
12:55
We're similar at the genetic level.
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ืื ื• ื“ื•ืžื™ื ื‘ืจืžื” ื”ื’ื ื˜ื™ืช.
12:58
And what we're finding
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ื•ืžื” ืฉืื ื• ืžื•ืฆืื™ื, ืฉืœืžืขืฉื”,
13:00
is actually, even at the brain biochemical level,
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ืืคื™ืœื• ื‘ืจืžื” ื”ื‘ื™ื•ื›ื™ืžื™ืช ืฉืœ ื”ืžื•ื—,
13:02
we are quite similar.
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ืื ื• ื“ื™ ื“ื•ืžื™ื.
13:04
And so this shows it's not 99 percent,
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ื›ืืŸ ืจื•ืื™ื ืฉื–ื” ืœื 99 ืื—ื•ื–,
13:06
but it's roughly 90 percent correspondence
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ืืœื ื‘ืงื™ืจื•ื‘ 90 ืื—ื•ื– ืฉืœ ื”ืชืืžื”
13:08
at a reasonable cutoff,
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ื‘ื—ืชืš ืžื™ื™ืฆื’, ื›ืš ืฉื”ื›ืœ ื‘ืชื•ืš
13:11
so everything in the cloud is roughly correlated.
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ื”ืขื ืŸ ื“ื™ ืชื•ืื ืื—ื“ ืœืฉื ื™.
13:13
And then we find some outliers,
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ืื‘ืœ ืื ื• ืžื•ืฆืื™ื ื›ืžื” ืžื—ื•ืฅ ืœืชื—ื•ื,
13:15
some things that lie beyond the cloud.
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ื›ืžื” ื”ื ืžืฆืื™ื ืžื—ื•ืฅ ืœืขื ืŸ.
13:18
And those genes are interesting,
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ื”ื’ื ื™ื ื”ืœืœื• ืžืขื•ืจืจื™ื ืขื ื™ื™ืŸ,
13:20
but they're very subtle.
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ืื‘ืœ ื”ื”ื‘ื“ืœื™ื ืžืื•ื“ ืขื“ื™ื ื™ื.
13:22
So I think it's an important message
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ืœื›ืŸ ืื ื™ ืกื‘ื•ืจ ืฉื–ื” ืžืกืจ ื—ืฉื•ื‘
13:25
to take home today
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ืœืงื—ืช ื”ื™ื•ื ื”ื‘ื™ืชื”
13:27
that even though we celebrate all of our differences,
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ื•ื”ื•ื ืฉืœืžืจื•ืช ืฉืื ื• ืžืฉื‘ื—ื™ื ืืช ื”ื ื‘ื“ืœื•ืช ื‘ื™ื ื™ื ื•,
13:30
we are quite similar
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ืื ื• ื“ื™ ื“ื•ืžื™ื
13:32
even at the brain level.
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ืืคื™ืœื• ื‘ืจืžืช ื”ืžื•ื—.
13:34
Now what do those differences look like?
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ืื™ืš ื ืจืื™ื ื”ื”ื‘ื“ืœื™ื ื”ืœืœื•?
13:36
This is an example of a study that we did
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ื–ื•ื”ื™ ื“ื•ื’ืžื ืœืžื—ืงืจ ืฉืขืฉื™ื ื•
13:38
to follow up and see what exactly those differences were --
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ื›ื“ื™ ืœืขืงื•ื‘ ื•ืœืจืื•ืช ืžื” ื”ื ื‘ื“ื™ื•ืง ื”ื”ื‘ื“ืœื™ื --
13:40
and they're quite subtle.
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ื•ื”ื ื“ื™ ืขื“ื™ื ื™ื.
13:42
These are things where genes are turned on in an individual cell type.
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ืืœื” ื”ื ื”ื“ื‘ืจื™ื ื‘ื’ืœืœื ื’ื ื™ื ืžืชืขื•ืจืจื™ื ื‘ืชืื™ื ืžืกื•ื™ื™ืžื™ื ื‘ืœื‘ื“.
13:46
These are two genes that we found as good examples.
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ืืœื” ื”ื ืฉื ื™ ื’ื ื™ื ืฉืžืฆืื ื• ื›ื“ื•ื’ืžืื•ืช ื˜ื•ื‘ื•ืช.
13:49
One is called RELN -- it's involved in early developmental cues.
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ืื—ื“ ื ืงืจื RELN -- ืงืฉื•ืจ ื‘ืื•ืชื•ืช ื”ืชืคืชื—ื•ืชื™ื™ื ืžื•ืงื“ืžื™ื.
13:52
DISC1 is a gene
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DISC1 ื”ื•ื ื’ืŸ
13:54
that's deleted in schizophrenia.
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ืฉื ืฉืžื˜ ื‘ืกื›ื™ื–ื•ืคืจื ื™ื”.
13:56
These aren't schizophrenic individuals,
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ืืœื” ืœื ืื ืฉื™ื ืกื›ื™ื–ื•ืคืจื ื™ื™ื,
13:58
but they do show some population variation.
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ืื‘ืœ ื”ื ื›ืŸ ืžืฆื™ื’ื™ื ืฉื•ื ื™ ืžื”ืื•ื›ืœื•ืกื™ื” ื”ืจื’ื™ืœื”.
14:01
And so what you're looking at here
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ืื– ืžื” ืฉืจื•ืื™ื ื›ืืŸ
14:03
in donor one and donor four,
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ื‘ืชื•ืจื 1 ื•ืชื•ืจื 4,
14:05
which are the exceptions to the other two,
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ืฉื”ื ืฉื•ื ื™ื ืžืฉื ื™ ื”ืื—ืจื™ื,
14:07
that genes are being turned on
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ืฉื’ื ื™ื ืžื•ืคืขืœื™ื
14:09
in a very specific subset of cells.
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ื‘ืžืขืจื›ื•ืช-ืžื™ืฉื ื” ืžืื•ื“ ืžืกื•ื™ื™ืžื•ืช ืฉืœ ืชืื™ื.
14:11
It's this dark purple precipitate within the cell
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ืืœื” ื”ื›ืชืžื™ื ื”ื›ื”ื™ื ื”ืกื’ื•ืœื™ื ื‘ืชื•ืš ื”ืชื
14:14
that's telling us a gene is turned on there.
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ื”ืื•ืžืจื™ื ืœื ื• ืฉื’ืŸ ื”ื•ืคืขืœ ืฉื.
14:17
Whether or not that's due
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ืื ื–ื” ื‘ื’ืœืœ ื”ืจืงืข ื”ื’ื ื˜ื™ ืฉืœ ืื•ืชื• ืื“ื
14:19
to an individual's genetic background or their experiences,
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ืื• ื‘ื’ืœืœ ื—ื•ื•ื™ื•ืชื™ื•,
14:21
we don't know.
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ืื™ื ื ื• ื™ื•ื“ืขื™ื.
14:23
Those kinds of studies require much larger populations.
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ืžื—ืงืจื™ื ื›ืืœื” ื“ื•ืจืฉื™ื ืื•ื›ืœื•ืกื™ื•ืช ื”ืจื‘ื” ื™ื•ืชืจ ื’ื“ื•ืœื•ืช.
14:28
So I'm going to leave you with a final note
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ืœืกื™ื•ื ืืฉืื™ืจ ืืชื›ื ืขื ื”ืขืจื” ืื—ืจื•ื ื”
14:30
about the complexity of the brain
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ืขืœ ืžื•ืจื›ื‘ื•ืช ื”ืžื•ื—
14:33
and how much more we have to go.
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ื•ืขื“ ื›ืžื” ื”ืจื‘ื” ืขื•ื“ ืขืœื™ื ื• ืœืขื‘ื•ืจ.
14:35
I think these resources are incredibly valuable.
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ืื ื™ ืกื‘ื•ืจ ืฉืžืื’ืจื™ ืžื™ื“ืข ืืœื” ื—ืฉื•ื‘ื™ื ืขื“ ืžืื•ื“.
14:37
They give researchers a handle
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ื”ื ื ื•ืชื ื™ื ืœื—ื•ืงืจื™ื ื›ื™ื•ื•ืŸ
14:39
on where to go.
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ืœืืŸ ืœื”ืชืงื“ื.
14:41
But we only looked at a handful of individuals at this point.
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ืื‘ืœ ื‘ื“ืงื ื• ืจืง ืงื•ืžืฅ ืื ืฉื™ื ื‘ืฉืœื‘ ื–ื”.
14:44
We're certainly going to be looking at more.
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ื‘ื˜ื•ื— ืฉื ื‘ื“ื•ืง ืขื•ื“.
14:46
I'll just close by saying
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ืืกื™ื™ื ื‘ืื•ืžืจื™
14:48
that the tools are there,
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ืฉื”ื›ืœื™ื ื›ื‘ืจ ืงื™ื™ืžื™ื,
14:50
and this is truly an unexplored, undiscovered continent.
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ื•ื–ื•ื”ื™ ื‘ืืžืช ื™ื‘ืฉืช ืฉืœืžื” ืฉืขื“ื™ื™ืŸ ืœื ื ืชื’ืœืชื” ื•ืœื ื ื—ืงืจื”.
14:54
This is the new frontier, if you will.
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ืื ืชืจืฆื•, ื–ื•ื”ื™ ื”ื—ื–ื™ืช ื”ื—ื“ืฉื”.
14:58
And so for those who are undaunted,
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ื•ืœื›ืŸ ืขื‘ื•ืจ ื›ืœ ืืœื” ื”ืขืฉื•ื™ื™ื ืœืœื ื—ืช
15:00
but humbled by the complexity of the brain,
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ืื‘ืœ ื—ืฉื™ื ืขื ื•ื•ื” ืžื•ืœ ืžื•ืจื›ื‘ื•ืช ื”ืžื•ื—,
15:02
the future awaits.
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ื”ืขืชื™ื“ ืžื—ื›ื” ืœื›ื.
15:04
Thanks.
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ืชื•ื“ื”.
15:06
(Applause)
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(ืžื—ื™ืื•ืช ื›ืคื™ื™ื)

Original video on YouTube.com
ืขืœ ืืชืจ ื–ื”

ืืชืจ ื–ื” ื™ืฆื™ื’ ื‘ืคื ื™ื›ื ืกืจื˜ื•ื ื™ YouTube ื”ืžื•ืขื™ืœื™ื ืœืœื™ืžื•ื“ ืื ื’ืœื™ืช. ืชื•ื›ืœื• ืœืจืื•ืช ืฉื™ืขื•ืจื™ ืื ื’ืœื™ืช ื”ืžื•ืขื‘ืจื™ื ืขืœ ื™ื“ื™ ืžื•ืจื™ื ืžื”ืฉื•ืจื” ื”ืจืืฉื•ื ื” ืžืจื—ื‘ื™ ื”ืขื•ืœื. ืœื—ืฅ ืคืขืžื™ื™ื ืขืœ ื”ื›ืชื•ื‘ื™ื•ืช ื‘ืื ื’ืœื™ืช ื”ืžื•ืฆื’ื•ืช ื‘ื›ืœ ื“ืฃ ื•ื™ื“ืื• ื›ื“ื™ ืœื”ืคืขื™ืœ ืืช ื”ืกืจื˜ื•ืŸ ืžืฉื. ื”ื›ืชื•ื‘ื™ื•ืช ื’ื•ืœืœื•ืช ื‘ืกื ื›ืจื•ืŸ ืขื ื”ืคืขืœืช ื”ื•ื•ื™ื“ืื•. ืื ื™ืฉ ืœืš ื”ืขืจื•ืช ืื• ื‘ืงืฉื•ืช, ืื ื ืฆื•ืจ ืื™ืชื ื• ืงืฉืจ ื‘ืืžืฆืขื•ืช ื˜ื•ืคืก ื™ืฆื™ืจืช ืงืฉืจ ื–ื”.

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