0:00:00.359,0:00:04.355 This is a thousand-year-old drawing of the brain. 0:00:04.355,0:00:06.267 It's a diagram of the visual system. 0:00:06.267,0:00:09.017 And some things look very familiar today. 0:00:09.017,0:00:13.384 Two eyes at the bottom, optic nerve flowing out from the back. 0:00:13.384,0:00:15.504 There's a very large nose 0:00:15.504,0:00:18.821 that doesn't seem to be connected to anything in particular. 0:00:18.821,0:00:20.521 And if we compare this 0:00:20.521,0:00:22.595 to more recent representations of the visual system, 0:00:22.595,0:00:25.552 you'll see that things have gotten substantially more complicated 0:00:25.552,0:00:27.125 over the intervening thousand years. 0:00:27.125,0:00:30.090 And that's because today we can see what's inside of the brain, 0:00:30.090,0:00:32.571 rather than just looking at its overall shape. 0:00:32.571,0:00:36.550 Imagine you wanted to understand how a computer works 0:00:36.550,0:00:39.729 and all you could see was a keyboard, a mouse, a screen. 0:00:39.729,0:00:42.125 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, 0:00:44.167,0:00:46.011 look at the wiring inside. 0:00:46.011,0:00:47.875 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. 0:00:49.875,0:00:51.755 Nobody had had a glimpse of the brain's wiring. 0:00:51.755,0:00:54.707 And that's because if you take a brain out of the skull 0:00:54.707,0:00:56.396 and you cut a thin slice of it, 0:00:56.396,0:00:58.894 put it under even a very powerful microscope, 0:00:58.894,0:01:00.075 there's nothing there. 0:01:00.075,0:01:01.688 It's gray, formless. 0:01:01.688,0:01:04.292 There's no structure. It won't tell you anything. 0:01:04.292,0:01:07.146 And this all changed in the late 19th century. 0:01:07.146,0:01:11.021 Suddenly, new chemical stains for brain tissue were developed 0:01:11.021,0:01:13.833 and they gave us our first glimpses at brain wiring. 0:01:13.833,0:01:15.846 The computer was cracked open. 0:01:15.846,0:01:18.702 So what really launched modern neuroscience 0:01:18.702,0:01:20.667 was a stain called the Golgi stain. 0:01:20.667,0:01:22.548 And it works in a very particular way. 0:01:22.548,0:01:25.658 Instead of staining all of the cells inside of a tissue, 0:01:25.658,0:01:28.690 it somehow only stains about one percent of them. 0:01:28.690,0:01:32.032 It clears the forest, reveals the trees inside. 0:01:32.032,0:01:34.704 If everything had been labeled, nothing would have been visible. 0:01:34.704,0:01:36.750 So somehow it shows what's there. 0:01:36.750,0:01:39.417 Spanish neuroanatomist Santiago Ramon y Cajal, 0:01:39.417,0:01:42.262 who's widely considered the father of modern neuroscience, 0:01:42.262,0:01:46.159 applied this Golgi stain, which yields data which looks like this, 0:01:46.159,0:01:49.917 and really gave us the modern notion of the nerve cell, the neuron. 0:01:49.917,0:01:52.531 And if you're thinking of the brain as a computer, 0:01:52.531,0:01:54.542 this is the transistor. 0:01:54.542,0:01:56.617 And very quickly Cajal realized 0:01:56.617,0:01:58.954 that neurons don't operate alone, 0:01:58.954,0:02:00.792 but rather make connections with others 0:02:00.792,0:02:03.298 that form circuits just like in a computer. 0:02:03.298,0:02:06.689 Today, a century later, when researchers want to visualize neurons, 0:02:06.689,0:02:09.456 they light them up from the inside rather than darkening them. 0:02:09.456,0:02:10.606 And there's several ways of doing this. 0:02:10.606,0:02:12.333 But one of the most popular ones 0:02:12.333,0:02:14.425 involves green fluorescent protein. 0:02:14.425,0:02:16.084 Now green fluorescent protein, 0:02:16.084,0:02:19.229 which oddly enough comes from a bioluminescent jellyfish, 0:02:19.229,0:02:20.467 is very useful. 0:02:20.467,0:02:23.105 Because if you can get the gene for green fluorescent protein 0:02:23.105,0:02:24.780 and deliver it to a cell, 0:02:24.780,0:02:26.527 that cell will glow green -- 0:02:26.527,0:02:30.273 or any of the many variants now of green fluorescent 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, 0:02:33.458,0:02:37.258 this is from a genetically engineered mouse called "Brainbow." 0:02:37.258,0:02:38.808 And it's so called, of course, 0:02:38.808,0:02:42.420 because all of these neurons are glowing different colors. 0:02:42.420,0:02:45.871 Now sometimes neuroscientists need to identify 0:02:45.871,0:02:48.915 individual molecular components of neurons, molecules, 0:02:48.915,0:02:50.713 rather than the entire cell. 0:02:50.713,0:02:52.419 And there's several ways of doing this, 0:02:52.419,0:02:53.888 but one of the most popular ones 0:02:53.888,0:02:56.083 involves using antibodies. 0:02:56.083,0:02:57.420 And you're familiar, of course, 0:02:57.420,0:03:00.371 with antibodies as the henchmen of the immune system. 0:03:00.371,0:03:02.789 But it turns out that they're so useful to the immune system 0:03:02.789,0:03:05.339 because they can recognize specific molecules, 0:03:05.339,0:03:07.458 like, for example, the coat protein 0:03:07.458,0:03:09.846 of a virus that's invading the body. 0:03:09.846,0:03:11.891 And researchers have used this fact 0:03:11.891,0:03:16.216 in order to recognize specific molecules inside of the brain, 0:03:16.216,0:03:18.856 recognize specific substructures of the cell 0:03:18.856,0:03:21.100 and identify them individually. 0:03:21.100,0:03:24.125 And a lot of the images I've been showing you here are very beautiful, 0:03:24.125,0:03:26.031 but they're also very powerful. 0:03:26.031,0:03:27.667 They have great explanatory power. 0:03:27.667,0:03:29.757 This, for example, is an antibody staining 0:03:29.757,0:03:33.277 against serotonin transporters in a slice of mouse brain. 0:03:33.277,0:03:34.958 And you've heard of serotonin, of course, 0:03:34.958,0:03:37.785 in the context of diseases like depression and anxiety. 0:03:37.785,0:03:39.193 You've heard of SSRIs, 0:03:39.193,0:03:42.090 which are drugs that are used to treat these diseases. 0:03:42.090,0:03:44.980 And in order to understand how serotonin works, 0:03:44.980,0:03:48.056 it's critical to understand where the serontonin machinery is. 0:03:48.056,0:03:49.652 And antibody stainings like this one 0:03:49.652,0:03:53.198 can be used to understand that sort of question. 0:03:53.198,0:03:55.756 I'd like to leave you with the following thought: 0:03:55.756,0:03:58.366 Green fluorescent protein and antibodies 0:03:58.366,0:04:01.373 are both totally natural products at the get-go. 0:04:01.373,0:04:04.152 They were evolved by nature 0:04:04.152,0:04:06.719 in order to get a jellyfish to glow green for whatever reason, 0:04:06.719,0:04:11.102 or in order to detect the coat protein of an invading virus, for example. 0:04:11.102,0:04:14.119 And only much later did scientists come onto the scene 0:04:14.119,0:04:16.142 and say, "Hey, these are tools, 0:04:16.142,0:04:18.255 these are functions that we could use 0:04:18.255,0:04:20.263 in our own research tool palette." 0:04:20.263,0:04:23.891 And instead of applying feeble human minds 0:04:23.891,0:04:25.775 to designing these tools from scratch, 0:04:25.775,0:04:28.679 there were these ready-made solutions right out there in nature 0:04:28.679,0:04:31.915 developed and refined steadily for millions of years 0:04:31.915,0:04:33.615 by the greatest engineer of all. 0:04:33.615,0:04:34.877 Thank you. 0:04:34.877,0:04:37.415 (Applause)