1 00:00:00,325 --> 00:00:05,642 What I'm going to show you are the astonishing molecular machines 2 00:00:05,666 --> 00:00:08,966 that create the living fabric of your body. 3 00:00:08,990 --> 00:00:12,773 Now molecules are really, really tiny. 4 00:00:12,797 --> 00:00:15,677 And by tiny, I mean really. 5 00:00:16,645 --> 00:00:18,647 They're smaller than a wavelength of light, 6 00:00:18,671 --> 00:00:20,976 so we have no way to directly observe them. 7 00:00:21,751 --> 00:00:24,094 But through science, we do have a fairly good idea 8 00:00:24,118 --> 00:00:26,330 of what's going on down at the molecular scale. 9 00:00:26,799 --> 00:00:29,576 So what we can do is actually tell you about the molecules, 10 00:00:29,600 --> 00:00:32,837 but we don't really have a direct way of showing you the molecules. 11 00:00:32,861 --> 00:00:35,111 One way around this is to draw pictures. 12 00:00:35,135 --> 00:00:37,675 And this idea is actually nothing new. 13 00:00:37,699 --> 00:00:39,987 Scientists have always created pictures 14 00:00:40,011 --> 00:00:42,797 as part of their thinking and discovery process. 15 00:00:42,821 --> 00:00:45,696 They draw pictures of what they're observing with their eyes, 16 00:00:45,720 --> 00:00:48,112 through technology like telescopes and microscopes, 17 00:00:48,136 --> 00:00:50,575 and also what they're thinking about in their minds. 18 00:00:50,599 --> 00:00:52,202 I picked two well-known examples, 19 00:00:52,226 --> 00:00:55,831 because they're very well-known for expressing science through art. 20 00:00:56,180 --> 00:00:59,883 And I start with Galileo, who used the world's first telescope 21 00:00:59,907 --> 00:01:01,093 to look at the Moon. 22 00:01:01,117 --> 00:01:03,424 And he transformed our understanding of the Moon. 23 00:01:03,448 --> 00:01:05,081 The perception in the 17th century 24 00:01:05,105 --> 00:01:07,162 was the Moon was a perfect heavenly sphere. 25 00:01:07,575 --> 00:01:10,559 But what Galileo saw was a rocky, barren world, 26 00:01:10,583 --> 00:01:12,976 which he expressed through his watercolor painting. 27 00:01:13,411 --> 00:01:16,209 Another scientist with very big ideas, 28 00:01:16,334 --> 00:01:18,858 the superstar of biology is Charles Darwin. 29 00:01:18,882 --> 00:01:20,926 And with this famous entry in his notebook, 30 00:01:20,950 --> 00:01:23,790 he begins in the top left-hand corner with, "I think," 31 00:01:23,814 --> 00:01:26,521 and then sketches out the first tree of life, 32 00:01:26,545 --> 00:01:29,475 which is his perception of how all the species, 33 00:01:29,499 --> 00:01:33,357 all living things on Earth are connected through evolutionary history -- 34 00:01:33,381 --> 00:01:35,628 the origin of species through natural selection 35 00:01:35,652 --> 00:01:37,976 and divergence from an ancestral population. 36 00:01:38,515 --> 00:01:39,976 Even as a scientist, 37 00:01:40,388 --> 00:01:42,901 I used to go to lectures by molecular biologists 38 00:01:42,925 --> 00:01:45,650 and find them completely incomprehensible, 39 00:01:45,674 --> 00:01:47,942 with all the fancy technical language and jargon 40 00:01:47,966 --> 00:01:50,090 that they would use in describing their work, 41 00:01:50,114 --> 00:01:53,165 until I encountered the artworks of David Goodsell, 42 00:01:53,189 --> 00:01:55,930 who is a molecular biologist at the Scripps Institute. 43 00:01:55,954 --> 00:01:59,523 And his pictures -- everything's accurate and it's all to scale. 44 00:01:59,547 --> 00:02:01,976 And his work illuminated for me 45 00:02:02,000 --> 00:02:04,315 what the molecular world inside us is like. 46 00:02:04,815 --> 00:02:06,840 So this is a transection through blood. 47 00:02:06,864 --> 00:02:09,841 In the top left-hand corner, you've got this yellow-green area. 48 00:02:09,865 --> 00:02:13,081 The yellow-green area is the fluid of blood, which is mostly water, 49 00:02:13,105 --> 00:02:16,092 but it's also antibodies, sugars, hormones, that kind of thing. 50 00:02:16,116 --> 00:02:18,604 And the red region is a slice into a red blood cell. 51 00:02:18,628 --> 00:02:20,494 And those red molecules are hemoglobin. 52 00:02:20,518 --> 00:02:23,213 They are actually red; that's what gives blood its color. 53 00:02:23,237 --> 00:02:25,204 And hemoglobin acts as a molecular sponge 54 00:02:25,228 --> 00:02:26,905 to soak up the oxygen in your lungs 55 00:02:26,929 --> 00:02:29,042 and then carry it to other parts of the body. 56 00:02:29,066 --> 00:02:31,598 I was very much inspired by this image many years ago, 57 00:02:31,622 --> 00:02:34,173 and I wondered whether we could use computer graphics 58 00:02:34,197 --> 00:02:35,801 to represent the molecular world. 59 00:02:35,825 --> 00:02:36,976 What would it look like? 60 00:02:37,000 --> 00:02:38,440 And that's how I really began. 61 00:02:38,863 --> 00:02:40,476 So let's begin. 62 00:02:40,500 --> 00:02:42,885 This is DNA in its classic double helix form. 63 00:02:42,909 --> 00:02:46,265 And it's from X-ray crystallography, so it's an accurate model of DNA. 64 00:02:46,289 --> 00:02:49,260 If we unwind the double helix and unzip the two strands, 65 00:02:49,284 --> 00:02:51,303 you see these things that look like teeth. 66 00:02:51,327 --> 00:02:53,144 Those are the letters of genetic code, 67 00:02:53,168 --> 00:02:55,437 the 25,000 genes you've got written in your DNA. 68 00:02:55,461 --> 00:02:58,397 This is what they typically talk about -- the genetic code -- 69 00:02:58,421 --> 00:03:00,112 this is what they're talking about. 70 00:03:00,136 --> 00:03:02,906 But I want to talk about a different aspect of DNA science, 71 00:03:02,930 --> 00:03:04,819 and that is the physical nature of DNA. 72 00:03:04,843 --> 00:03:07,428 It's these two strands that run in opposite directions 73 00:03:07,452 --> 00:03:09,622 for reasons I can't go into right now. 74 00:03:09,646 --> 00:03:11,854 But they physically run in opposite directions, 75 00:03:11,878 --> 00:03:15,509 which creates a number of complications for your living cells, 76 00:03:15,533 --> 00:03:16,762 as you're about to see, 77 00:03:16,786 --> 00:03:19,148 most particularly when DNA is being copied. 78 00:03:19,172 --> 00:03:21,090 And so what I'm about to show you 79 00:03:21,114 --> 00:03:25,130 is an accurate representation of the actual DNA replication machine 80 00:03:25,154 --> 00:03:27,211 that's occurring right now inside your body, 81 00:03:27,235 --> 00:03:29,047 at least 2002 biology. 82 00:03:29,357 --> 00:03:32,368 So DNA's entering the production line from the left-hand side, 83 00:03:32,734 --> 00:03:35,901 and it hits this collection, these miniature biochemical machines, 84 00:03:35,925 --> 00:03:39,069 that are pulling apart the DNA strand and making an exact copy. 85 00:03:39,093 --> 00:03:42,602 So DNA comes in and hits this blue, doughnut-shaped structure 86 00:03:42,626 --> 00:03:44,933 and it's ripped apart into its two strands. 87 00:03:45,419 --> 00:03:47,043 One strand can be copied directly, 88 00:03:47,067 --> 00:03:49,990 and you can see these things spooling off to the bottom there. 89 00:03:50,014 --> 00:03:52,274 But things aren't so simple for the other strand 90 00:03:52,298 --> 00:03:54,063 because it must be copied backwards. 91 00:03:54,087 --> 00:03:56,197 So it's thrown out repeatedly in these loops 92 00:03:56,221 --> 00:04:00,265 and copied one section at a time, creating two new DNA molecules. 93 00:04:00,289 --> 00:04:05,572 Now you have billions of this machine right now working away inside you, 94 00:04:05,596 --> 00:04:07,813 copying your DNA with exquisite fidelity. 95 00:04:08,676 --> 00:04:10,210 It's an accurate representation, 96 00:04:10,234 --> 00:04:13,763 and it's pretty much at the correct speed for what is occurring inside you. 97 00:04:13,787 --> 00:04:16,604 I've left out error correction and a bunch of other things. 98 00:04:16,628 --> 00:04:18,387 (Laughter) 99 00:04:18,411 --> 00:04:20,532 This was work from a number of years ago-- 100 00:04:20,556 --> 00:04:21,725 Thank you. 101 00:04:21,749 --> 00:04:23,121 (Applause) 102 00:04:23,145 --> 00:04:25,074 This is work from a number of years ago, 103 00:04:25,098 --> 00:04:27,365 but what I'll show you next is updated science, 104 00:04:27,389 --> 00:04:28,551 it's updated technology. 105 00:04:28,575 --> 00:04:29,935 So again, we begin with DNA. 106 00:04:29,959 --> 00:04:31,677 And it's jiggling and wiggling there 107 00:04:31,701 --> 00:04:33,882 because of the surrounding soup of molecules, 108 00:04:33,906 --> 00:04:36,289 which I've stripped away so you can see something. 109 00:04:36,313 --> 00:04:39,288 DNA is about two nanometers across, which is really quite tiny. 110 00:04:39,312 --> 00:04:40,746 But in each one of your cells, 111 00:04:40,770 --> 00:04:43,947 each strand of DNA is about 30 to 40 million nanometers long. 112 00:04:44,414 --> 00:04:48,230 So to keep the DNA organized and regulate access to the genetic code, 113 00:04:48,254 --> 00:04:50,337 it's wrapped around these purple proteins -- 114 00:04:50,361 --> 00:04:51,943 or I've labeled them purple here. 115 00:04:51,967 --> 00:04:53,551 It's packaged up and bundled up. 116 00:04:53,575 --> 00:04:55,976 All this field of view is a single strand of DNA. 117 00:04:56,511 --> 00:04:59,593 This huge package of DNA is called a chromosome. 118 00:04:59,617 --> 00:05:01,976 And we'll come back to chromosomes in a minute. 119 00:05:02,415 --> 00:05:04,481 We're pulling out, we're zooming out, 120 00:05:04,505 --> 00:05:05,976 out through a nuclear pore, 121 00:05:06,000 --> 00:05:09,660 which is the gateway to this compartment that holds all the DNA, 122 00:05:09,684 --> 00:05:11,103 called the nucleus. 123 00:05:11,657 --> 00:05:15,888 All of this field of view is about a semester's worth of biology, 124 00:05:15,912 --> 00:05:17,277 and I've got seven minutes, 125 00:05:17,301 --> 00:05:19,989 So we're not going to be able to do that today? 126 00:05:20,013 --> 00:05:21,975 No, I'm being told, "No." 127 00:05:22,416 --> 00:05:25,781 This is the way a living cell looks down a light microscope. 128 00:05:25,805 --> 00:05:29,303 And it's been filmed under time-lapse, which is why you can see it moving. 129 00:05:29,327 --> 00:05:30,908 The nuclear envelope breaks down. 130 00:05:30,932 --> 00:05:33,177 These sausage-shaped things are the chromosomes, 131 00:05:33,201 --> 00:05:34,382 and we'll focus on them. 132 00:05:34,406 --> 00:05:38,444 They go through this very striking motion that is focused on these little red spots. 133 00:05:39,068 --> 00:05:43,303 When the cell feels it's ready to go, it rips apart the chromosome. 134 00:05:43,327 --> 00:05:45,368 One set of DNA goes to one side, 135 00:05:45,392 --> 00:05:47,415 the other side gets the other set of DNA -- 136 00:05:47,439 --> 00:05:49,276 identical copies of DNA. 137 00:05:49,300 --> 00:05:51,260 And then the cell splits down the middle. 138 00:05:51,284 --> 00:05:54,143 And again, you have billions of cells undergoing this process 139 00:05:54,167 --> 00:05:55,524 right now inside of you. 140 00:05:56,342 --> 00:05:59,198 Now we're going to rewind and just focus on the chromosomes, 141 00:05:59,222 --> 00:06:01,464 and look at its structure and describe it. 142 00:06:01,988 --> 00:06:04,413 So again, here we are at that equator moment. 143 00:06:05,394 --> 00:06:06,594 The chromosomes line up. 144 00:06:06,618 --> 00:06:08,445 And if we isolate just one chromosome, 145 00:06:08,469 --> 00:06:11,286 we're going to pull it out and have a look at its structure. 146 00:06:11,310 --> 00:06:14,372 So this is one of the biggest molecular structures that you have, 147 00:06:14,396 --> 00:06:17,451 at least as far as we've discovered so far inside of us. 148 00:06:18,026 --> 00:06:20,002 So this is a single chromosome. 149 00:06:20,026 --> 00:06:22,627 And you have two strands of DNA in each chromosome. 150 00:06:22,651 --> 00:06:24,372 One is bundled up into one sausage. 151 00:06:24,396 --> 00:06:27,129 The other strand is bundled up into the other sausage. 152 00:06:27,153 --> 00:06:30,715 These things that look like whiskers that are sticking out from either side 153 00:06:30,739 --> 00:06:32,645 are the dynamic scaffolding of the cell. 154 00:06:32,669 --> 00:06:35,580 They're called microtubules, that name's not important. 155 00:06:35,604 --> 00:06:38,335 But we're going to focus on the region labeled red here -- 156 00:06:38,359 --> 00:06:40,896 and it's the interface between the dynamic scaffolding 157 00:06:40,920 --> 00:06:42,087 and the chromosomes. 158 00:06:42,111 --> 00:06:45,216 It is obviously central to the movement of the chromosomes. 159 00:06:45,240 --> 00:06:48,812 We have no idea, really, as to how it's achieving that movement. 160 00:06:48,836 --> 00:06:51,483 We've been studying this thing they call the kinetochore 161 00:06:51,507 --> 00:06:53,579 for over a hundred years with intense study, 162 00:06:53,603 --> 00:06:56,429 and we're still just beginning to discover what it's about. 163 00:06:56,453 --> 00:06:59,207 It is made up of about 200 different types of proteins, 164 00:06:59,231 --> 00:07:00,942 thousands of proteins in total. 165 00:07:01,730 --> 00:07:04,550 It is a signal broadcasting system. 166 00:07:04,574 --> 00:07:06,738 It broadcasts through chemical signals, 167 00:07:06,762 --> 00:07:09,506 telling the rest of the cell when it's ready, 168 00:07:09,530 --> 00:07:12,361 when it feels that everything is aligned and ready to go 169 00:07:12,385 --> 00:07:14,363 for the separation of the chromosomes. 170 00:07:14,387 --> 00:07:17,719 It is able to couple onto the growing and shrinking microtubules. 171 00:07:17,743 --> 00:07:20,942 It's involved with the growing of the microtubules, 172 00:07:20,966 --> 00:07:23,369 and it's able to transiently couple onto them. 173 00:07:24,099 --> 00:07:25,919 It's also an attention-sensing system. 174 00:07:25,943 --> 00:07:27,919 It's able to feel when the cell is ready, 175 00:07:27,943 --> 00:07:30,177 when the chromosome is correctly positioned. 176 00:07:30,201 --> 00:07:34,014 It's turning green here because it feels that everything is just right. 177 00:07:34,038 --> 00:07:36,296 And you'll see, there's this one little last bit 178 00:07:36,320 --> 00:07:37,753 that's still remaining red. 179 00:07:37,777 --> 00:07:40,310 And it's walked away down the microtubules. 180 00:07:41,889 --> 00:07:45,068 That is the signal broadcasting system sending out the stop signal. 181 00:07:45,092 --> 00:07:47,788 And it's walked away -- I mean, it's that mechanical. 182 00:07:47,812 --> 00:07:49,380 It's molecular clockwork. 183 00:07:49,404 --> 00:07:51,976 This is how you work at the molecular scale. 184 00:07:52,609 --> 00:07:54,873 So with a little bit of molecular eye candy, 185 00:07:54,897 --> 00:07:56,095 (Laughter) 186 00:07:56,119 --> 00:07:58,069 we've got kinesins, the orange ones. 187 00:07:58,093 --> 00:08:00,866 They're little molecular courier molecules walking one way. 188 00:08:00,890 --> 00:08:04,036 And here are the dynein, they're carrying that broadcasting system. 189 00:08:04,060 --> 00:08:05,604 And they've got their long legs 190 00:08:05,628 --> 00:08:07,694 so they can step around obstacles and so on. 191 00:08:07,718 --> 00:08:10,745 So again, this is all derived accurately from the science. 192 00:08:10,769 --> 00:08:13,319 The problem is we can't show it to you any other way. 193 00:08:13,343 --> 00:08:18,177 Exploring at the frontier of science, at the frontier of human understanding, 194 00:08:18,201 --> 00:08:19,436 is mind-blowing. 195 00:08:20,714 --> 00:08:21,892 Discovering this stuff 196 00:08:21,916 --> 00:08:25,444 is certainly a pleasurable incentive to work in science. 197 00:08:25,960 --> 00:08:27,688 But most medical researchers -- 198 00:08:28,641 --> 00:08:32,854 discovering the stuff is simply steps along the path to the big goals, 199 00:08:32,878 --> 00:08:37,299 which are to eradicate disease, to eliminate the suffering 200 00:08:37,323 --> 00:08:39,398 and the misery that disease causes 201 00:08:39,422 --> 00:08:41,102 and to lift people out of poverty. 202 00:08:41,126 --> 00:08:42,398 Thank you. 203 00:08:42,422 --> 00:08:47,619 (Applause)