WEBVTT 00:00:17.503 --> 00:00:21.343 I want to tell you today about three areas of science and engineering 00:00:21.343 --> 00:00:24.313 that I think are converging in very interesting ways. 00:00:24.844 --> 00:00:26.597 I'm a mechanical engineer. 00:00:26.597 --> 00:00:28.831 I've been working in robotics for over 25 years. 00:00:28.831 --> 00:00:31.828 I've been in micro/nanotechnologies for over 15 years. 00:00:31.828 --> 00:00:34.527 And over the past decade, since I've been here in Zurich, 00:00:34.527 --> 00:00:37.912 I've been working more closely with biologists and with medical doctors, 00:00:37.912 --> 00:00:40.246 and I think that the technologies we're working on 00:00:40.246 --> 00:00:43.677 and our vision of the future has some very interesting implications. 00:00:43.677 --> 00:00:45.391 But instead of telling you about it, 00:00:45.391 --> 00:00:48.260 what I want to show you is a clip from a Hollywood film 00:00:48.260 --> 00:00:51.310 that actually happens to be almost as old as I am, so ... 00:01:03.537 --> 00:01:05.489 (Video) Man: All stations, stand by. 00:01:05.489 --> 00:01:07.719 (On stage) (Laughter) 00:01:08.380 --> 00:01:10.430 (Video) Man: Right. Inject. 00:01:24.823 --> 00:01:26.966 (On stage) "Fantastic Voyage," it's a classic. 00:01:26.966 --> 00:01:28.221 I love this movie. 00:01:28.521 --> 00:01:32.003 Hollywood has two advantages when they make movies, versus an engineer. 00:01:32.003 --> 00:01:33.857 They don't have to worry about physics. 00:01:33.857 --> 00:01:36.141 They don't have actually have to make the things. 00:01:36.141 --> 00:01:37.430 What I want to show you now 00:01:37.430 --> 00:01:40.338 is an animation actually made for us by the Discovery Channel. 00:01:40.338 --> 00:01:43.019 They visited my lab about a year and a half ago. 00:01:43.019 --> 00:01:45.015 We appeared on one of their shows, 00:01:45.015 --> 00:01:47.819 and they put together this concept of where we're heading. 00:01:47.819 --> 00:01:50.249 And what we've been working on for several years now 00:01:50.249 --> 00:01:54.230 have been little, what we call microrobots that we inject into your eye - 00:01:54.230 --> 00:01:56.149 we haven't done it on a human yet, 00:01:56.156 --> 00:01:58.691 but we inject it into your eye - 00:01:58.691 --> 00:02:02.325 and we use magnetic fields to guide that device back to the retina 00:02:02.325 --> 00:02:05.509 to perform certain retinal therapies, for instance delivering drugs. 00:02:05.509 --> 00:02:07.257 You saw there, over the patient, 00:02:07.257 --> 00:02:10.725 the sequence of electromagnetic coils that we use. 00:02:10.725 --> 00:02:13.436 This is in a real pig's eye that you're seeing right here. 00:02:13.436 --> 00:02:16.153 This pig's eye came from the butcher earlier that morning, 00:02:16.153 --> 00:02:19.794 so we didn't harm any animals ourselves in making this, but - 00:02:19.794 --> 00:02:20.794 (Laughter) 00:02:20.794 --> 00:02:24.344 What you see is that we're able to very precisely control that device. 00:02:24.344 --> 00:02:26.598 That device is about 0.5 mm in size, 00:02:26.598 --> 00:02:29.811 about a millimeter long, to give you an idea of scale. 00:02:29.811 --> 00:02:31.678 And in this next slide, 00:02:31.678 --> 00:02:36.208 you'll see on the left is a system of electromagnetic coils we use. 00:02:36.208 --> 00:02:38.607 We do in vivo animal trials with these. 00:02:38.607 --> 00:02:40.108 There are eight of these coils, 00:02:40.108 --> 00:02:41.210 we call it the OctoMag, 00:02:41.210 --> 00:02:44.119 and we control the current in each one of those very precisely 00:02:44.119 --> 00:02:46.309 to guide this device through the ocular cavity 00:02:46.309 --> 00:02:47.480 back to the retina. 00:02:47.480 --> 00:02:50.989 You'll see one of our most recent devices on the fingertip there. 00:02:50.989 --> 00:02:52.939 That particular, we call it a microrobot; 00:02:52.939 --> 00:02:58.269 it's about 1/3 mm in diameter, 330 microns in diameter. 00:02:58.269 --> 00:02:59.731 And our design specs - 00:02:59.731 --> 00:03:01.712 the reason we want it to be so thin - 00:03:01.712 --> 00:03:03.757 it's about 1.8 mm long - 00:03:03.757 --> 00:03:06.567 is that we want it to fit inside of a 23-gauge needle. 00:03:06.845 --> 00:03:10.164 If it fits inside of a 23-gauge needle and we inject it into your eye, 00:03:10.164 --> 00:03:14.046 as we remove that, that puncture wound doesn't need a suture. 00:03:14.046 --> 00:03:16.165 It's relatively non-invasive. 00:03:16.165 --> 00:03:18.793 You just put a little topical anesthetic, and it's done. 00:03:18.793 --> 00:03:22.762 All the time to inject drugs to treat age-related macular degeneration - 00:03:22.762 --> 00:03:24.529 that needle, not the microrobots, 00:03:24.529 --> 00:03:25.569 I should say. 00:03:25.920 --> 00:03:29.469 But that robot that I just showed you, that you see there on the fingertip, 00:03:29.469 --> 00:03:31.424 is the biggest robot we make. 00:03:31.424 --> 00:03:35.195 My goal is to make robots that are about 1000 times smaller than that, 00:03:35.195 --> 00:03:38.389 something the size, for instance, of these E. coli bacteria. 00:03:38.389 --> 00:03:42.316 These little rod-shaped bacteria are about a micron or two long. 00:03:42.316 --> 00:03:44.636 That is about 1/100 of the width of a hair. 00:03:45.494 --> 00:03:47.936 See those little tails coming off of them? 00:03:47.936 --> 00:03:50.043 We'll get to that later, okay? 00:03:50.043 --> 00:03:52.047 But before we start talking about bacteria, 00:03:52.047 --> 00:03:55.762 I want to talk a little bit about physics and what these constraints put on us, 00:03:55.762 --> 00:03:58.336 so we're going to do a simple thought experiment here. 00:03:58.336 --> 00:04:00.124 Let's take a cube, okay? 00:04:00.124 --> 00:04:01.582 It's a meter on the side. 00:04:01.582 --> 00:04:04.116 And I don't need my calculator to do this calculation. 00:04:04.116 --> 00:04:07.068 A meter by a meter by a meter is a cubic meter, right? 00:04:07.068 --> 00:04:10.594 But if I take that cube and I shrink it to 10 cm - 00:04:10.594 --> 00:04:12.362 I shrink it by a factor of 10 - 00:04:12.362 --> 00:04:13.820 that calculation changes 00:04:13.820 --> 00:04:16.250 because I'm taking a length by a length by a length, 00:04:16.250 --> 00:04:20.233 and all of a sudden, it's become 1/1000th of its original volume, 00:04:20.233 --> 00:04:22.853 and so properties that depend on volume - 00:04:22.853 --> 00:04:24.044 for instance, mass - 00:04:24.044 --> 00:04:25.855 also go down by a factor of 1000. 00:04:25.855 --> 00:04:29.106 Now, if I go down another 100 times, to a centimeter, 00:04:29.106 --> 00:04:31.414 it's gone down, now, by a million times. 00:04:31.414 --> 00:04:32.409 And so volume - 00:04:32.409 --> 00:04:35.130 as I said, the weight of it goes down by a million times, 00:04:35.130 --> 00:04:39.650 but also those magnetic forces we generate on it are also going down 00:04:39.650 --> 00:04:42.182 because they scale also with the mass of the object. 00:04:42.772 --> 00:04:46.849 So you might say, "But since it weighs less, what's the problem?" 00:04:46.849 --> 00:04:50.091 But now, let's think about the surface area of that cube. 00:04:50.091 --> 00:04:52.893 It's got six sides, each side is a square meter. 00:04:52.893 --> 00:04:55.713 It's got six square meters on that cube. 00:04:55.713 --> 00:04:57.872 Over the volume of one, ratio of six. 00:04:57.872 --> 00:05:00.943 But as I go down, that area is only a length by a length, 00:05:00.943 --> 00:05:04.882 and so as I go down each order of magnitude by a factor of 10, 00:05:04.882 --> 00:05:08.007 the importance of surface area goes up by a factor of 10. 00:05:08.007 --> 00:05:09.600 And that causes problems, okay? 00:05:09.600 --> 00:05:10.833 I can't make robots 00:05:10.833 --> 00:05:14.598 and guide them with magnetic fields the way I showed you in the eye - 00:05:14.598 --> 00:05:17.418 I can't make them any smaller than I have. 00:05:17.418 --> 00:05:19.783 So what are some of the implications? 00:05:19.783 --> 00:05:21.922 Well, think about a fish and how a fish swims. 00:05:21.922 --> 00:05:25.316 A fish moves its tail back and forth in a reciprocal motion. 00:05:25.316 --> 00:05:29.898 It's pushing the mass of fluid back and moving itself forward. 00:05:29.898 --> 00:05:32.554 It knows Newton's first law, okay? 00:05:32.554 --> 00:05:34.840 And so, Geoffrey Taylor, professor at Cambridge, 00:05:34.840 --> 00:05:38.272 thought about this and published some very important papers in the 1950s, 00:05:38.272 --> 00:05:41.892 and he made a little mechanical fish just to show how it would work in water, 00:05:41.892 --> 00:05:44.086 and it swims just the way you'd think it would. 00:05:44.086 --> 00:05:45.260 But if I took that fish 00:05:45.260 --> 00:05:48.085 or I took you, and I made you 1,000 or 10,000 times smaller, 00:05:48.085 --> 00:05:50.989 and I put you in water, all of sudden, that water would feel - 00:05:50.989 --> 00:05:52.798 even though it has the same viscocity, 00:05:52.798 --> 00:05:54.893 the surface effects or the drag of that water 00:05:54.893 --> 00:05:56.825 would be much, much stronger on you. 00:05:56.825 --> 00:05:58.509 And so what Geoffrey Taylor did - 00:05:58.509 --> 00:06:00.830 this is a video he made in the 1960s - 00:06:00.830 --> 00:06:04.062 is he got a vat of something very thick. 00:06:04.062 --> 00:06:06.918 I think if you're from the UK, you know Lyle's Golden Syrup, 00:06:06.918 --> 00:06:09.725 and I think that's what he must have used if you look at it. 00:06:09.725 --> 00:06:12.008 So, he took his robot - 00:06:12.008 --> 00:06:13.543 it's a little mechanical fish - 00:06:13.543 --> 00:06:17.044 put it in there, and it doesn't go anywhere 00:06:17.044 --> 00:06:18.836 because the fluid drag is so strong 00:06:18.836 --> 00:06:21.549 and the mass that's pushing back is so much less than that 00:06:21.549 --> 00:06:22.555 that it doesn't move. 00:06:22.555 --> 00:06:24.844 And that's the problem as we go down in scale, 00:06:24.844 --> 00:06:30.144 is that we have to rethink the way things swim 00:06:30.144 --> 00:06:31.404 and the way things move. 00:06:31.869 --> 00:06:35.160 Well, if you're an engineer and you don't know how to solve a problem, 00:06:35.160 --> 00:06:36.158 what do you do? 00:06:36.158 --> 00:06:39.263 You look at nature and think, "How did nature solve this problem?" 00:06:39.263 --> 00:06:43.002 Nature solved this problem millions, billions of years ago. 00:06:43.002 --> 00:06:44.564 We know there's paramecia. 00:06:44.564 --> 00:06:46.568 You see the spermatozoa there on the right? 00:06:46.568 --> 00:06:49.470 And they have these special little hairs on them, these cilia, 00:06:49.470 --> 00:06:52.063 these flagella for the sperm, we call them, 00:06:52.063 --> 00:06:53.859 that move in very interesting ways. 00:06:53.859 --> 00:06:58.016 Now, nobody knew before 1675 that these things even existed. 00:06:58.016 --> 00:07:01.622 Antonie van Leeuwenhoek, in Holland, was looking in his microscope, 00:07:01.622 --> 00:07:02.694 and he was astounded 00:07:02.694 --> 00:07:06.028 to see a world of tens of thousands of little microorganisms swimming, 00:07:06.028 --> 00:07:08.690 and he wrote a letter to the Royal Society the next year. 00:07:08.690 --> 00:07:10.041 They verified his results. 00:07:10.041 --> 00:07:12.013 People were astounded, what was going on. 00:07:12.013 --> 00:07:16.244 And what van Leeuwenhoek saw in his microscope 00:07:16.244 --> 00:07:20.384 was the first time anybody had ever seen bacteria. 00:07:21.072 --> 00:07:24.972 This is a graphic of one of the rod-shaped ones. 00:07:24.972 --> 00:07:26.512 It's about a micron or two long. 00:07:27.702 --> 00:07:30.154 And as you look at these under a microscope - 00:07:30.154 --> 00:07:32.326 you saw the one I showed of the E.coli - 00:07:32.326 --> 00:07:34.417 you'll notice it has a little flagella on it. 00:07:34.417 --> 00:07:36.373 And as you look at it under a microscope, 00:07:36.373 --> 00:07:39.695 what you see is this flagella seems to be wiggling back and forth, 00:07:39.695 --> 00:07:42.403 but if you were able to look at it from another direction, 00:07:42.403 --> 00:07:45.643 you realize it's not wiggling back and forth; it's actually rotating. 00:07:46.398 --> 00:07:47.396 And Howard Berg, 00:07:47.396 --> 00:07:51.542 when he was at University of Colorado in the early 1970s, discovered this, 00:07:51.542 --> 00:07:54.166 and what he discovered was astounding: 00:07:54.166 --> 00:07:56.472 nature has invented a rotary motor. 00:07:56.472 --> 00:07:57.468 Think about it. 00:07:57.468 --> 00:08:00.152 Where else in nature is there a rotary motor? 00:08:00.152 --> 00:08:05.912 And Howard has been to our lab and given us some advice on what to do. 00:08:05.912 --> 00:08:08.999 He calls these things nature's microrobots, okay? 00:08:08.999 --> 00:08:14.079 So the body of the bacteria has sensors on it, chemoreceptors. 00:08:14.079 --> 00:08:17.169 Those chemoreceptors communicate with the motor in the back of it, 00:08:17.169 --> 00:08:18.327 to drive it. 00:08:18.327 --> 00:08:19.856 That also has software in there. 00:08:19.856 --> 00:08:22.187 The software is the chunks of DNA floating around. 00:08:22.187 --> 00:08:24.295 They're just telling it what parts to make 00:08:24.295 --> 00:08:27.723 to keep building the sensors it needs, the motors it needs, and all that. 00:08:27.723 --> 00:08:29.940 And the motor is a fascinating structure. 00:08:29.940 --> 00:08:34.291 Since Howard discovered these bacterial motors in 1973 - 00:08:34.291 --> 00:08:37.970 which, by the way some people believe is evidence of an intelligent designer, 00:08:37.970 --> 00:08:41.430 but I don't think most biologists believe that. 00:08:43.518 --> 00:08:47.828 These motors are made from about 30 to 40 proteins. 00:08:48.188 --> 00:08:50.651 They assemble into this structure 00:08:50.651 --> 00:08:54.106 that spins up to 160 revolutions per second. 00:08:54.106 --> 00:08:56.806 And you see on the right here, a video from Howard's lab 00:08:56.806 --> 00:09:00.658 of fluorescent bacteria swimming at these speeds. 00:09:00.658 --> 00:09:03.238 Remember that the size of these is a micron or two. 00:09:04.663 --> 00:09:07.378 So we looked at this, and we were thinking, 00:09:07.378 --> 00:09:08.762 "What can we learn from this? 00:09:08.762 --> 00:09:10.432 How can we take advantage of this?" 00:09:10.432 --> 00:09:15.442 So we leveraged some of our nanotechnology experience 00:09:15.442 --> 00:09:18.641 to build something we called an artificial bacterial flagella. 00:09:18.641 --> 00:09:20.253 Now, I can't make that motor yet. 00:09:20.253 --> 00:09:22.702 That motor's about 45 nanometers in diameter. 00:09:22.702 --> 00:09:24.475 But what I can make is the flagella 00:09:24.475 --> 00:09:27.162 of a similar size and shape that a bacteria has. 00:09:27.162 --> 00:09:30.738 And on the front of it there on the left, you'll see what looks like a head, 00:09:30.738 --> 00:09:33.265 and what that is is actually a little piece of magnet, 00:09:33.265 --> 00:09:35.142 and what I can do with that magnet 00:09:35.142 --> 00:09:38.685 is I can generate a torque on it with a magnetic field, 00:09:38.685 --> 00:09:40.068 and as I rotate that field - 00:09:40.068 --> 00:09:41.787 and these are very, very low fields; 00:09:41.787 --> 00:09:44.073 they're about 1000 times less than an MRI field - 00:09:44.073 --> 00:09:45.507 they start to get it to twist, 00:09:45.507 --> 00:09:47.761 and as it twists, it propels itself forward, 00:09:47.761 --> 00:09:49.551 just like E. coli do. 00:09:50.217 --> 00:09:52.688 To give you an idea of the scale we're talking about, 00:09:52.688 --> 00:09:55.286 here's a scanning electron micrograph of a human hair; 00:09:55.286 --> 00:09:57.661 it's about 100 microns or so in diameter. 00:09:58.191 --> 00:10:00.477 There is the size of our smallest ABFs. 00:10:00.477 --> 00:10:03.406 They're about 10 microns, these particular ones. 00:10:03.406 --> 00:10:05.610 And this is the size of a red blood cell, okay? 00:10:05.610 --> 00:10:06.710 So we're about double. 00:10:06.710 --> 00:10:09.664 Our smallest ones are about twice the size of a red blood cell. 00:10:09.664 --> 00:10:13.481 And here are three of them swimming together in a sort of swarm behavior. 00:10:13.481 --> 00:10:14.719 To me, they look alive. 00:10:14.719 --> 00:10:16.921 I get excited when we do this, you know? 00:10:16.921 --> 00:10:17.915 (Laughter) 00:10:17.915 --> 00:10:19.107 That's why I do robotics. 00:10:19.107 --> 00:10:22.464 There's nothing more fun than building a machine and watching it move. 00:10:22.464 --> 00:10:24.905 Now, you'll notice these will start to go backwards. 00:10:24.905 --> 00:10:27.431 I didn't reverse the video; I just reversed the field. 00:10:27.431 --> 00:10:30.569 There's some really interesting fluid dynamics to be explored here, 00:10:30.569 --> 00:10:32.006 and that's pretty interesting. 00:10:32.006 --> 00:10:35.284 One exciting thing for us this year was when we were in the bookstore, 00:10:35.284 --> 00:10:38.265 we picked up a copy of the 2012 Guinness Book of World Records 00:10:38.265 --> 00:10:41.317 and discovered that we were in the Guinness Book of World Records 00:10:41.317 --> 00:10:43.003 for the smallest medical robot. 00:10:43.003 --> 00:10:44.003 (Audience) Whoo! 00:10:44.003 --> 00:10:47.242 Bradley Nelson: Being in the Guinness Book of World Records is great, 00:10:47.242 --> 00:10:48.908 but what I'm really gunning for is, 00:10:48.908 --> 00:10:50.983 I want to win a medal in the next Olympics, 00:10:50.983 --> 00:10:53.129 and so we're developing synchronized swimmers. 00:10:53.129 --> 00:10:54.131 (Laughter) 00:10:54.681 --> 00:10:55.781 These are interesting - 00:10:55.781 --> 00:10:58.373 What's particularly interesting about these guys 00:10:58.373 --> 00:11:00.278 is that they're made out of a polymer. 00:11:00.278 --> 00:11:01.548 They're noncytotoxic. 00:11:01.548 --> 00:11:02.635 They don't kill cells; 00:11:02.635 --> 00:11:04.363 in fact, cells like to grow on them. 00:11:04.363 --> 00:11:06.083 And we've developed a new technology 00:11:06.083 --> 00:11:08.747 that allows us to make some fairly arbitrary shapes here. 00:11:08.747 --> 00:11:11.080 So in this next little video I want to show you 00:11:11.080 --> 00:11:12.826 is one of our devices. 00:11:12.826 --> 00:11:14.156 We put a claw on it, 00:11:14.156 --> 00:11:17.718 and so what it can do is go around and grab these little - 00:11:17.718 --> 00:11:19.343 these are 6-micron diameter beads, 00:11:19.343 --> 00:11:21.679 so they're about the size of that red blood cell - 00:11:21.679 --> 00:11:25.260 grab those, move them up in 3D, move them up and down, 00:11:25.260 --> 00:11:28.860 and then eventually release them using these fluidic forces. 00:11:33.396 --> 00:11:37.047 We've also been thinking about other, more serious applications as well. 00:11:37.047 --> 00:11:38.391 Here's one of our devices. 00:11:38.391 --> 00:11:41.448 We coated it with a fluorescent molecule called calcein. 00:11:41.448 --> 00:11:45.441 This molecule, you're looking at it in a fluorescent microscope there. 00:11:46.101 --> 00:11:48.201 This molecule, actually, 00:11:48.201 --> 00:11:51.011 is the same molecular weight as a lot of chemotherapy drugs. 00:11:51.011 --> 00:11:57.551 And on the left, you'll see some red cells that are stained red. 00:11:57.979 --> 00:12:02.239 We discovered as we moved this bacteria near those cells and touched them with it, 00:12:02.247 --> 00:12:04.743 the calcein actually gets taken up by the cells. 00:12:04.743 --> 00:12:09.573 So this allows us, now, to potentially deliver drugs into individual cells 00:12:09.573 --> 00:12:12.357 and target individual cells with this kind of technology. 00:12:12.357 --> 00:12:13.738 The other thing that's cool - 00:12:13.738 --> 00:12:16.548 I've only shown you a few, but we can make armies of these. 00:12:16.548 --> 00:12:18.168 We can make them by the thousands. 00:12:18.168 --> 00:12:19.718 We can make about one a second. 00:12:19.718 --> 00:12:22.097 We make tens of thousands, put them in suspension. 00:12:22.097 --> 00:12:24.621 So I think there's some interesting possibilities here 00:12:24.621 --> 00:12:28.441 for the future of where this can go. 00:12:29.068 --> 00:12:30.985 So let's go back to the bacterial motor. 00:12:30.985 --> 00:12:34.286 This is a video from Keiichi Namba's lab at Osaka University. 00:12:34.286 --> 00:12:35.856 He and his group have spent years 00:12:35.856 --> 00:12:38.288 trying to understand the exact sequence of proteins, 00:12:38.288 --> 00:12:40.240 how they assemble into this rotary motor. 00:12:40.240 --> 00:12:43.102 And while I'm not at the point where I can develop the motor, 00:12:43.102 --> 00:12:45.564 I can develop some of these parts of this device, 00:12:45.564 --> 00:12:49.325 and so what we're hoping as we move into the future and keep going in this area, 00:12:49.325 --> 00:12:52.279 we'll learn more and more from nature at these molecular scales 00:12:52.279 --> 00:12:54.999 and be able to build machines that operate in similar ways 00:12:54.999 --> 00:12:56.382 and under similar principles. 00:12:57.032 --> 00:13:00.037 I've been very fortunate to work with some brilliant scientists, 00:13:00.037 --> 00:13:02.296 brilliant medical doctors, 00:13:02.296 --> 00:13:03.586 and when you're at the ETH, 00:13:03.586 --> 00:13:05.830 the Swiss Federal Institute of Technology here - 00:13:05.830 --> 00:13:07.326 you know, I'm an engineer. 00:13:07.326 --> 00:13:12.276 I walk the hallways where people like Conrad Röntgen, who invented X-rays, 00:13:12.276 --> 00:13:14.296 Wolfgang Pauli or Albert Einstein were. 00:13:14.296 --> 00:13:16.058 It's a humbling experience. 00:13:16.058 --> 00:13:19.724 So I take a little bit of comfort 00:13:19.724 --> 00:13:23.315 in a quote from a famous aeronautical engineer from Caltech, 00:13:23.315 --> 00:13:25.036 Theodore von Karman, 00:13:25.036 --> 00:13:26.839 and von Karman said, 00:13:26.839 --> 00:13:31.099 "The scientist describes what is; the engineer creates what never was." 00:13:31.099 --> 00:13:32.097 (Laughter) 00:13:32.097 --> 00:13:33.387 Okay. So. 00:13:34.304 --> 00:13:36.491 I want to leave you with one last thought here. 00:13:36.491 --> 00:13:39.496 This is from Richard Feynman, the famous physicist from Caltech, 00:13:39.496 --> 00:13:41.978 who said, "What I cannot make, I do not understand." 00:13:41.978 --> 00:13:42.977 (Laughter) 00:13:42.977 --> 00:13:44.357 Okay. So thank you very much. 00:13:44.357 --> 00:13:45.364 (Applause)