0:00:00.359,0:00:03.663 This is a thousand-year-old drawing of the brain. 0:00:03.663,0:00:05.667 It's a diagram of the visual system. 0:00:05.667,0:00:08.125 And some things look very familiar today. 0:00:08.125,0:00:12.292 Two eyes at the bottom, optic nerve flowing out from the back. 0:00:12.292,0:00:14.750 There's a very large nose 0:00:14.750,0:00:17.667 that doesn't seem to be connected to anything in particular. 0:00:17.667,0:00:19.583 And if we compare this 0:00:19.583,0:00:21.333 to more recent representations of the visual system, 0:00:21.333,0:00:24.583 you'll see that things have gotten substantially more complicated 0:00:24.583,0:00:27.125 over the intervening thousand years. 0:00:27.125,0:00:28.875 And that's because today we can see what's inside of the brain, 0:00:28.875,0:00:31.833 rather than just looking at its overall shape. 0:00:31.833,0:00:35.458 Imagine you wanted to understand how a computer works 0:00:35.458,0:00:38.083 and all you could see was a keyboard, a mouse, a screen. 0:00:38.083,0:00:42.125 You really would be kind of out of luck. 0:00:42.125,0:00:44.167 You want to be able to open it up, crack it open, 0:00:44.167,0:00:45.042 look at the wiring inside. 0:00:45.042,0:00:47.875 And up until a little more than a century ago, 0:00:47.875,0:00:49.875 nobody was able to do that with the brain. 0:00:49.875,0:00:51.417 Nobody had had a glimpse of the brain's wiring. 0:00:51.417,0:00:54.292 And that's because if you take a brain out of the skull 0:00:54.292,0:00:56.042 and you cut a thin slice of it, 0:00:56.042,0:00:58.125 put it under a very powerful microscope, 0:00:58.125,0:00:59.875 there's nothing there. 0:00:59.875,0:01:00.750 It's gray, formless. 0:01:00.750,0:01:04.292 There's no structure. It won't tell you anything. 0:01:04.292,0:01:06.208 And this all changed in the late 19th century. 0:01:06.208,0:01:09.667 Suddenly, new chemical stains for brain tissue were developed 0:01:09.667,0:01:13.833 and they gave us our first glimpses at brain wiring. 0:01:13.833,0:01:15.000 The computer was cracked open. 0:01:15.000,0:01:17.333 So what really launched modern neuroscience 0:01:17.333,0:01:20.667 was a stain called the Golgi stain. 0:01:20.667,0:01:22.333 And it works in a very particular way. 0:01:22.333,0:01:24.750 Instead of staining all of the cells inside of a tissue, 0:01:24.750,0:01:27.306 it somehow only stains about one percent of them. 0:01:27.306,0:01:31.017 It clears the forest, reveals the trees inside. 0:01:31.017,0:01:34.042 If everything had been labeled, nothing would have been visible. 0:01:34.042,0:01:36.750 So somehow it shows what's there. 0:01:36.750,0:01:39.417 Spanish neuroanatomist Santiago Ramon y Cajal, 0:01:39.417,0:01:40.708 who's widely considered the father of modern neuroscience, 0:01:40.708,0:01:44.667 applied this Golgi stain, which yields data which looks like this, 0:01:44.667,0:01:49.917 and really gave us the modern notion of the nerve cell, the neuron. 0:01:49.917,0:01:51.500 And if you're thinking of the brain as a computer, 0:01:51.500,0:01:54.542 this is the transistor. 0:01:54.542,0:01:55.417 And very quickly Cajal realized 0:01:55.417,0:01:58.323 that neurons don't operate alone, 0:01:58.323,0:02:00.792 but rather make connections with others 0:02:00.792,0:02:03.298 that form circuits just like in a computer. 0:02:03.298,0:02:04.458 Today, a century later, when researchers want to visualize neurons, 0:02:04.458,0:02:08.625 they light them up from the inside rather than darkening them. 0:02:08.625,0:02:10.375 And there's several ways of doing this. 0:02:10.375,0:02:12.333 But one of the most popular ones 0:02:12.333,0:02:13.917 involves green florescent protein. 0:02:13.917,0:02:14.792 Now green florescent protein, 0:02:14.792,0:02:17.167 which oddly enough comes from a bioluminescent jellyfish, 0:02:17.167,0:02:18.765 is very useful. 0:02:18.765,0:02:22.167 Because if you can get the gene for green florescent protein 0:02:22.167,0:02:24.227 and deliver it to a cell, 0:02:24.227,0:02:25.434 that cell will glow green -- 0:02:25.434,0:02:30.273 or any of the many variants now of green florescent protein, 0:02:30.273,0:02:31.937 you get a cell to glow many different colors. 0:02:31.937,0:02:33.458 And so coming back to the brain, 0:02:33.458,0:02:36.750 this is from a genetically engineered mouse called Brainbow. 0:02:36.750,0:02:38.208 And it's so called, of course, 0:02:38.208,0:02:42.420 because all of these neurons are glowing different colors. 0:02:42.420,0:02:45.625 Now sometimes neuroscientists need to identify 0:02:45.625,0:02:48.500 individual molecular components of neurons, molecules, 0:02:48.500,0:02:50.375 rather than the entire cell. 0:02:50.375,0:02:51.250 And there's several ways of doing this, 0:02:51.250,0:02:52.125 but one of the most popular ones 0:02:52.125,0:02:56.083 involves using antibodies. 0:02:56.083,0:02:56.958 And you're familiar, of course, 0:02:56.958,0:02:57.833 with antibodies and the henchmen of the immune system. 0:02:57.833,0:03:01.958 But it turns out that they're so useful to the immune system 0:03:01.958,0:03:03.708 because they can recognize specific molecules, 0:03:03.708,0:03:07.458 like, for example, the code protein 0:03:07.458,0:03:09.708 of a virus that's invading the body. 0:03:09.708,0:03:10.583 And researchers have used this fact 0:03:10.583,0:03:14.708 in order to recognize specific molecules inside of the brain, 0:03:14.708,0:03:17.333 recognize specific substructures of the cell 0:03:17.333,0:03:20.500 and identify them individually. 0:03:20.500,0:03:24.125 And a lot of the images I've been showing you here are very beautiful, 0:03:24.125,0:03:25.000 but they're also very powerful. 0:03:25.000,0:03:27.667 They have great explanatory power. 0:03:27.667,0:03:28.542 This, for example, is an antibody staining 0:03:28.542,0:03:33.277 against serotonin transporters in a slice of mouse brain. 0:03:33.277,0:03:33.958 And you've heard of serotonin, of course, 0:03:33.958,0:03:36.708 in the context of diseases like depression and anxiety. 0:03:36.708,0:03:37.583 You've heard of SSRI's, 0:03:37.583,0:03:40.875 which are drugs that are used to treat these diseases. 0:03:40.875,0:03:44.042 And in order to understand how serotonin works, 0:03:44.042,0:03:47.625 it's critical to understand where the serontonin machinery is. 0:03:47.625,0:03:49.375 And antibody staining like this one 0:03:49.375,0:03:52.167 can be used to understand that sort of question. 0:03:52.167,0:03:54.125 I'd like to leave you with the following thought. 0:03:54.125,0:03:57.566 Green florescent protein and antibodies 0:03:57.566,0:03:58.958 are both totally natural products at the get-go. 0:03:58.958,0:04:04.152 They were evolved by nature 0:04:04.152,0:04:05.750 in order to get a jellyfish to glow green for whatever reason, 0:04:05.750,0:04:09.917 or in order to detect the code protein of an invading virus, for example. 0:04:09.917,0:04:12.750 And only much later did scientists come onto the scene 0:04:12.750,0:04:13.250 and say, "Hey, these are tools, 0:04:13.250,0:04:16.917 these are functions that we could use 0:04:16.917,0:04:18.667 in our own research tool pallet." 0:04:18.667,0:04:22.583 And instead of applying feeble human minds 0:04:22.583,0:04:23.458 to designing these tools from scratch, 0:04:23.458,0:04:26.833 there were these ready-made solutions right out there in nature 0:04:26.833,0:04:30.500 developed and refined steadily for millions of years 0:04:30.500,0:04:31.929 by the greatest engineer of all. 0:04:31.929,0:04:34.000 Thank you. 0:04:34.000,0:04:37.415 (Applause)