WEBVTT

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This is a thousand-year-old drawing of the brain.

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It's a diagram of the visual system.

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And some things look very familiar today.

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Two eyes at the bottom, optic nerve flowing out from the back.

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There's a very large nose

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that doesn't seem to be connected to anything in particular.

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And if we compare this

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to more recent representations of the visual system,

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you'll see that things have gotten substantially more complicated

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over the intervening thousand years.

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And that's because today we can see what's inside of the brain,

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rather than just looking at its overall shape.

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Imagine you wanted to understand how a computer works

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and all you could see was a keyboard, a mouse, a screen.

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You really would be kind of out of luck.

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You want to be able to open it up, crack it open,

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look at the wiring inside.

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And up until a little more than a century ago,

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nobody was able to do that with the brain.

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Nobody had had a glimpse of the brain's wiring.

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And that's because if you take a brain out of the skull

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and you cut a thin slice of it,

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put it under even a very powerful microscope,

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there's nothing there.

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It's gray, formless.

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There's no structure. It won't tell you anything.

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And this all changed in the late 19th century.

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Suddenly, new chemical stains for brain tissue were developed

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and they gave us our first glimpses at brain wiring.

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The computer was cracked open.

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So what really launched modern neuroscience

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was a stain called the Golgi stain.

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And it works in a very particular way.

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Instead of staining all of the cells inside of a tissue,

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it somehow only stains about one percent of them.

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It clears the forest, reveals the trees inside.

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If everything had been labeled, nothing would have been visible.

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So somehow it shows what's there.

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Spanish neuroanatomist Santiago Ramon y Cajal,

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who's widely considered the father of modern neuroscience,

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applied this Golgi stain, which yields data which looks like this,

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and really gave us the modern notion of the nerve cell, the neuron.

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And if you're thinking of the brain as a computer,

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this is the transistor.

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And very quickly Cajal realized

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that neurons don't operate alone,

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but rather make connections with others

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that form circuits just like in a computer.

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Today, a century later, when researchers want to visualize neurons,

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they light them up from the inside rather than darkening them.

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And there's several ways of doing this.

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But one of the most popular ones

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involves green fluorescent protein.

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Now green fluorescent protein,

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which oddly enough comes from a bioluminescent jellyfish,

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is very useful.

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Because if you can get the gene for green fluorescent protein

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and deliver it to a cell,

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that cell will glow green --

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or any of the many variants now of green fluorescent protein,

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you get a cell to glow many different colors.

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And so coming back to the brain,

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this is from a genetically engineered mouse called "Brainbow."

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And it's so called, of course,

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because all of these neurons are glowing different colors.

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Now sometimes neuroscientists need to identify

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individual molecular components of neurons, molecules,

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rather than the entire cell.

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And there's several ways of doing this,

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but one of the most popular ones

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involves using antibodies.

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And you're familiar, of course,

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with antibodies as the henchmen of the immune system.

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But it turns out that they're so useful to the immune system

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because they can recognize specific molecules,

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like, for example, the coat protein

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of a virus that's invading the body.

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And researchers have used this fact

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in order to recognize specific molecules inside of the brain,

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recognize specific substructures of the cell

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and identify them individually.

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And a lot of the images I've been showing you here are very beautiful,

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but they're also very powerful.

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They have great explanatory power.

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This, for example, is an antibody staining

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against serotonin transporters in a slice of mouse brain.

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And you've heard of serotonin, of course,

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in the context of diseases like depression and anxiety.

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You've heard of SSRIs,

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which are drugs that are used to treat these diseases.

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And in order to understand how serotonin works,

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it's critical to understand where the serontonin machinery is.

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And antibody stainings like this one

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can be used to understand that sort of question.

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I'd like to leave you with the following thought:

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Green fluorescent protein and antibodies

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are both totally natural products at the get-go.

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They were evolved by nature

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in order to get a jellyfish to glow green for whatever reason,

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or in order to detect the coat protein of an invading virus, for example.

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And only much later did scientists come onto the scene

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and say, "Hey, these are tools,

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these are functions that we could use

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in our own research tool palette."

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And instead of applying feeble human minds

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to designing these tools from scratch,

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there were these ready-made solutions right out there in nature

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developed and refined steadily for millions of years

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by the greatest engineer of all.

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Thank you.

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(Applause)