1 00:00:00,557 --> 00:00:04,235 In the space that used to house one transistor, 2 00:00:04,259 --> 00:00:07,098 we can now fit one billion. 3 00:00:07,636 --> 00:00:11,533 That made it so that a computer the size of an entire room 4 00:00:11,557 --> 00:00:14,146 now fits in your pocket. 5 00:00:14,170 --> 00:00:17,189 You might say the future is small. 6 00:00:17,611 --> 00:00:18,818 As an engineer, 7 00:00:18,842 --> 00:00:22,827 I'm inspired by this miniaturization revolution in computers. 8 00:00:22,851 --> 00:00:24,199 As a physician, 9 00:00:24,223 --> 00:00:29,946 I wonder whether we could use it to reduce the number of lives lost 10 00:00:29,970 --> 00:00:34,077 due to one of the fastest-growing diseases on Earth: 11 00:00:34,101 --> 00:00:35,519 cancer. 12 00:00:35,543 --> 00:00:36,798 Now when I say that, 13 00:00:36,822 --> 00:00:40,600 what most people hear me say is that we're working on curing cancer. 14 00:00:40,624 --> 00:00:41,887 And we are. 15 00:00:41,911 --> 00:00:43,062 But it turns out 16 00:00:43,086 --> 00:00:45,887 that there's an incredible opportunity to save lives 17 00:00:45,911 --> 00:00:49,244 through the early detection and prevention of cancer. 18 00:00:49,785 --> 00:00:55,164 Worldwide, over two-thirds of deaths due to cancer are fully preventable 19 00:00:55,188 --> 00:00:57,988 using methods that we already have in hand today. 20 00:00:58,406 --> 00:01:01,305 Things like vaccination, timely screening 21 00:01:01,329 --> 00:01:03,562 and of course, stopping smoking. 22 00:01:04,316 --> 00:01:07,909 But even with the best tools and technologies that we have today, 23 00:01:07,933 --> 00:01:09,996 some tumors can't be detected 24 00:01:10,020 --> 00:01:13,690 until 10 years after they've started growing, 25 00:01:13,714 --> 00:01:17,477 when they are 50 million cancer cells strong. 26 00:01:18,178 --> 00:01:19,857 What if we had better technologies 27 00:01:19,881 --> 00:01:22,987 to detect some of these more deadly cancers sooner, 28 00:01:23,011 --> 00:01:24,313 when they could be removed, 29 00:01:24,337 --> 00:01:26,538 when they were just getting started? 30 00:01:26,562 --> 00:01:29,837 Let me tell you about how miniaturization might get us there. 31 00:01:31,140 --> 00:01:33,428 This is a microscope in a typical lab 32 00:01:33,452 --> 00:01:37,008 that a pathologist would use for looking at a tissue specimen, 33 00:01:37,032 --> 00:01:39,470 like a biopsy or a pap smear. 34 00:01:39,927 --> 00:01:41,995 This $7,000 microscope 35 00:01:42,019 --> 00:01:45,275 would be used by somebody with years of specialized training 36 00:01:45,299 --> 00:01:47,088 to spot cancer cells. 37 00:01:48,126 --> 00:01:51,172 This is an image from a colleague of mine at Rice University, 38 00:01:51,196 --> 00:01:52,774 Rebecca Richards-Kortum. 39 00:01:52,798 --> 00:01:56,625 What she and her team have done is miniaturize that whole microscope 40 00:01:56,649 --> 00:01:58,624 into this $10 part, 41 00:01:58,648 --> 00:02:01,464 and it fits on the end of an optical fiber. 42 00:02:01,923 --> 00:02:05,557 Now what that means is instead of taking a sample from a patient 43 00:02:05,581 --> 00:02:07,230 and sending it to the microscope, 44 00:02:07,254 --> 00:02:09,810 you can bring the microscope to the patient. 45 00:02:10,260 --> 00:02:14,619 And then, instead of requiring a specialist to look at the images, 46 00:02:14,643 --> 00:02:19,705 you can train the computer to score normal versus cancerous cells. 47 00:02:20,084 --> 00:02:21,254 Now this is important, 48 00:02:21,278 --> 00:02:24,315 because what they found working in rural communities, 49 00:02:24,339 --> 00:02:27,578 is that even when they have a mobile screening van 50 00:02:27,602 --> 00:02:30,435 that can go out into the community and perform exams 51 00:02:30,459 --> 00:02:31,864 and collect samples 52 00:02:31,888 --> 00:02:35,104 and send them to the central hospital for analysis, 53 00:02:35,128 --> 00:02:36,472 that days later, 54 00:02:36,496 --> 00:02:39,163 women get a call with an abnormal test result 55 00:02:39,187 --> 00:02:40,804 and they're asked to come in. 56 00:02:40,828 --> 00:02:45,171 Fully half of them don't turn up because they can't afford the trip. 57 00:02:45,721 --> 00:02:49,145 With the integrated microscope and computer analysis, 58 00:02:49,169 --> 00:02:51,997 Rebecca and her colleagues have been able to create a van 59 00:02:52,021 --> 00:02:55,807 that has both a diagnostic setup and a treatment setup. 60 00:02:55,831 --> 00:02:58,545 And what that means is that they can do a diagnosis 61 00:02:58,569 --> 00:03:01,256 and perform therapy on the spot, 62 00:03:01,280 --> 00:03:03,418 so no one is lost to follow up. 63 00:03:03,831 --> 00:03:07,779 That's just one example of how miniaturization can save lives. 64 00:03:08,148 --> 00:03:09,301 Now as engineers, 65 00:03:09,325 --> 00:03:12,070 we think of this as straight-up miniaturization. 66 00:03:12,094 --> 00:03:14,531 You took a big thing and you made it little. 67 00:03:14,555 --> 00:03:16,806 But what I told you before about computers 68 00:03:16,830 --> 00:03:19,076 was that they transformed our lives 69 00:03:19,100 --> 00:03:23,401 when they became small enough for us to take them everywhere. 70 00:03:23,785 --> 00:03:28,081 So what is the transformational equivalent like that in medicine? 71 00:03:28,500 --> 00:03:31,636 Well, what if you had a detector 72 00:03:31,660 --> 00:03:35,922 that was so small that it could circulate in your body, 73 00:03:35,946 --> 00:03:38,359 find the tumor all by itself 74 00:03:38,383 --> 00:03:40,752 and send a signal to the outside world? 75 00:03:41,079 --> 00:03:43,156 It sounds a little bit like science fiction. 76 00:03:43,180 --> 00:03:47,083 But actually, nanotechnology allows us to do just that. 77 00:03:47,415 --> 00:03:52,296 Nanotechnology allows us to shrink the parts that make up the detector 78 00:03:52,320 --> 00:03:54,157 from the width of a human hair, 79 00:03:54,181 --> 00:03:55,841 which is 100 microns, 80 00:03:55,865 --> 00:03:58,420 to a thousand times smaller, 81 00:03:58,444 --> 00:04:00,346 which is 100 nanometers. 82 00:04:00,370 --> 00:04:03,180 And that has profound implications. 83 00:04:03,583 --> 00:04:07,226 It turns out that materials actually change their properties 84 00:04:07,250 --> 00:04:08,846 at the nanoscale. 85 00:04:09,279 --> 00:04:11,777 You take a common material like gold, 86 00:04:11,801 --> 00:04:15,122 and you grind it into dust, into gold nanoparticles, 87 00:04:15,146 --> 00:04:18,458 and it changes from looking gold to looking red. 88 00:04:19,082 --> 00:04:22,895 If you take a more exotic material like cadmium selenide -- 89 00:04:22,919 --> 00:04:25,093 forms a big, black crystal -- 90 00:04:25,117 --> 00:04:27,718 if you make nanocrystals out of this material 91 00:04:27,742 --> 00:04:29,315 and you put it in a liquid, 92 00:04:29,339 --> 00:04:31,163 and you shine light on it, 93 00:04:31,187 --> 00:04:32,353 they glow. 94 00:04:32,377 --> 00:04:38,008 And they glow blue, green, yellow, orange, red, 95 00:04:38,032 --> 00:04:40,307 depending only on their size. 96 00:04:40,887 --> 00:04:44,890 It's wild! Can you imagine an object like that in the macro world? 97 00:04:44,914 --> 00:04:51,485 It would be like all the denim jeans in your closet are all made of cotton, 98 00:04:51,509 --> 00:04:55,820 but they are different colors depending only on their size. 99 00:04:56,212 --> 00:04:57,908 (Laughter) 100 00:04:58,982 --> 00:05:00,506 So as a physician, 101 00:05:00,530 --> 00:05:02,754 what's just as interesting to me 102 00:05:02,778 --> 00:05:05,078 is that it's not just the color of materials 103 00:05:05,102 --> 00:05:07,033 that changes at the nanoscale; 104 00:05:07,057 --> 00:05:10,665 the way they travel in your body also changes. 105 00:05:11,137 --> 00:05:13,936 And this is the kind of observation that we're going to use 106 00:05:13,960 --> 00:05:16,134 to make a better cancer detector. 107 00:05:16,158 --> 00:05:17,911 So let me show you what I mean. 108 00:05:18,686 --> 00:05:20,883 This is a blood vessel in the body. 109 00:05:20,907 --> 00:05:23,318 Surrounding the blood vessel is a tumor. 110 00:05:23,683 --> 00:05:26,724 We're going to inject nanoparticles into the blood vessel 111 00:05:26,748 --> 00:05:30,928 and watch how they travel from the bloodstream into the tumor. 112 00:05:31,464 --> 00:05:35,816 Now it turns out that the blood vessels of many tumors are leaky, 113 00:05:35,840 --> 00:05:40,206 and so nanoparticles can leak out from the bloodstream into the tumor. 114 00:05:40,628 --> 00:05:43,762 Whether they leak out depends on their size. 115 00:05:44,129 --> 00:05:45,279 So in this image, 116 00:05:45,303 --> 00:05:49,674 the smaller, hundred-nanometer, blue nanoparticles are leaking out, 117 00:05:49,698 --> 00:05:53,094 and the larger, 500-nanometer, red nanoparticles 118 00:05:53,118 --> 00:05:54,895 are stuck in the bloodstream. 119 00:05:54,919 --> 00:05:57,022 So that means as an engineer, 120 00:05:57,046 --> 00:06:01,038 depending on how big or small I make a material, 121 00:06:01,062 --> 00:06:04,103 I can change where it goes in your body. 122 00:06:05,249 --> 00:06:09,891 In my lab, we recently made a cancer nanodetector 123 00:06:09,915 --> 00:06:15,163 that is so small that it could travel into the body and look for tumors. 124 00:06:15,477 --> 00:06:19,569 We designed it to listen for tumor invasion: 125 00:06:19,593 --> 00:06:24,366 the orchestra of chemical signals that tumors need to make to spread. 126 00:06:24,932 --> 00:06:27,834 For a tumor to break out of the tissue that it's born in, 127 00:06:27,858 --> 00:06:30,574 it has to make chemicals called enzymes 128 00:06:30,598 --> 00:06:33,182 to chew through the scaffolding of tissues. 129 00:06:33,763 --> 00:06:38,485 We designed these nanoparticles to be activated by these enzymes. 130 00:06:39,034 --> 00:06:44,946 One enzyme can activate a thousand of these chemical reactions in an hour. 131 00:06:45,462 --> 00:06:49,020 Now in engineering, we call that one-to-a-thousand ratio 132 00:06:49,044 --> 00:06:50,609 a form of amplification, 133 00:06:50,633 --> 00:06:52,805 and it makes something ultrasensitive. 134 00:06:52,829 --> 00:06:56,662 So we've made an ultrasensitive cancer detector. 135 00:06:57,220 --> 00:07:02,120 OK, but how do I get this activated signal to the outside world, 136 00:07:02,144 --> 00:07:03,882 where I can act on it? 137 00:07:03,906 --> 00:07:07,458 For this, we're going to use one more piece of nanoscale biology, 138 00:07:07,482 --> 00:07:09,266 and that has to do with the kidney. 139 00:07:09,659 --> 00:07:11,575 The kidney is a filter. 140 00:07:11,996 --> 00:07:16,625 Its job is to filter out the blood and put waste into the urine. 141 00:07:17,197 --> 00:07:19,859 It turns out that what the kidney filters 142 00:07:19,883 --> 00:07:22,445 is also dependent on size. 143 00:07:22,901 --> 00:07:24,841 So in this image, what you can see 144 00:07:24,865 --> 00:07:27,874 is that everything smaller than five nanometers 145 00:07:27,898 --> 00:07:32,003 is going from the blood, through the kidney, into the urine, 146 00:07:32,027 --> 00:07:34,697 and everything else that's bigger is retained. 147 00:07:35,176 --> 00:07:40,123 OK, so if I make a 100-nanometer cancer detector, 148 00:07:40,147 --> 00:07:42,619 I inject it in the bloodstream, 149 00:07:42,643 --> 00:07:48,073 it can leak into the tumor where it's activated by tumor enzymes 150 00:07:48,097 --> 00:07:50,453 to release a small signal 151 00:07:50,477 --> 00:07:53,699 that is small enough to be filtered out of the kidney 152 00:07:53,723 --> 00:07:55,901 and put into the urine, 153 00:07:55,925 --> 00:07:59,966 I have a signal in the outside world that I can detect. 154 00:08:00,588 --> 00:08:02,640 OK, but there's one more problem. 155 00:08:02,664 --> 00:08:04,410 This is a tiny little signal, 156 00:08:04,434 --> 00:08:06,406 so how do I detect it? 157 00:08:06,730 --> 00:08:08,965 Well, the signal is just a molecule. 158 00:08:08,989 --> 00:08:11,656 They're molecules that we designed as engineers. 159 00:08:11,680 --> 00:08:14,858 They're completely synthetic, and we can design them 160 00:08:14,882 --> 00:08:18,121 so they are compatible with our tool of choice. 161 00:08:18,145 --> 00:08:21,587 If we want to use a really sensitive, fancy instrument 162 00:08:21,611 --> 00:08:23,575 called a mass spectrometer, 163 00:08:23,599 --> 00:08:26,110 then we make a molecule with a unique mass. 164 00:08:26,671 --> 00:08:30,370 Or maybe we want make something that's more inexpensive and portable. 165 00:08:30,394 --> 00:08:34,177 Then we make molecules that we can trap on paper, 166 00:08:34,201 --> 00:08:35,905 like a pregnancy test. 167 00:08:35,929 --> 00:08:38,555 In fact, there's a whole world of paper tests 168 00:08:38,579 --> 00:08:43,091 that are becoming available in a field called paper diagnostics. 169 00:08:43,711 --> 00:08:46,037 Alright, where are we going with this? 170 00:08:46,724 --> 00:08:48,293 What I'm going to tell you next, 171 00:08:48,317 --> 00:08:50,143 as a lifelong researcher, 172 00:08:50,167 --> 00:08:52,046 represents a dream of mine. 173 00:08:52,396 --> 00:08:54,489 I can't say that's it's a promise; 174 00:08:54,513 --> 00:08:56,005 it's a dream. 175 00:08:56,029 --> 00:08:59,616 But I think we all have to have dreams to keep us pushing forward, 176 00:08:59,640 --> 00:09:03,577 even -- and maybe especially -- cancer researchers. 177 00:09:03,601 --> 00:09:07,100 I'm going to tell you what I hope will happen with my technology, 178 00:09:07,124 --> 00:09:11,215 that my team and I will put our hearts and souls 179 00:09:11,239 --> 00:09:12,761 into making a reality. 180 00:09:13,289 --> 00:09:14,987 OK, here goes. 181 00:09:15,011 --> 00:09:18,366 I dream that one day, 182 00:09:18,390 --> 00:09:21,645 instead of going into an expensive screening facility 183 00:09:21,669 --> 00:09:23,174 to get a colonoscopy, 184 00:09:23,198 --> 00:09:24,521 or a mammogram, 185 00:09:24,545 --> 00:09:25,953 or a pap smear, 186 00:09:26,585 --> 00:09:28,304 that you could get a shot, 187 00:09:28,328 --> 00:09:29,988 wait an hour, 188 00:09:30,012 --> 00:09:32,807 and do a urine test on a paper strip. 189 00:09:33,653 --> 00:09:36,460 I imagine that this could even happen 190 00:09:36,484 --> 00:09:39,147 without the need for steady electricity, 191 00:09:39,171 --> 00:09:41,775 or a medical professional in the room. 192 00:09:41,799 --> 00:09:43,296 Maybe they could be far away 193 00:09:43,320 --> 00:09:46,130 and connected only by the image on a smartphone. 194 00:09:46,854 --> 00:09:48,589 Now I know this sounds like a dream, 195 00:09:48,613 --> 00:09:51,732 but in the lab we already have this working in mice, 196 00:09:51,756 --> 00:09:53,835 where it works better than existing methods 197 00:09:53,859 --> 00:09:57,830 for the detection of lung, colon and ovarian cancer. 198 00:09:58,603 --> 00:10:00,837 And I hope that what this means 199 00:10:00,861 --> 00:10:06,037 is that one day we can detect tumors in patients 200 00:10:06,061 --> 00:10:09,354 sooner than 10 years after they've started growing, 201 00:10:09,378 --> 00:10:11,363 in all walks of life, 202 00:10:11,387 --> 00:10:13,236 all around the globe, 203 00:10:13,260 --> 00:10:15,995 and that this would lead to earlier treatments, 204 00:10:16,019 --> 00:10:19,617 and that we could save more lives than we can today, 205 00:10:19,641 --> 00:10:20,925 with early detection. 206 00:10:21,686 --> 00:10:22,868 Thank you. 207 00:10:22,892 --> 00:10:30,375 (Applause)