1 00:00:00,838 --> 00:00:03,021 Cancer affects all of us -- 2 00:00:03,045 --> 00:00:06,412 especially the ones that come back over and over again, 3 00:00:06,436 --> 00:00:09,432 the highly invasive and drug-resistant ones, 4 00:00:09,456 --> 00:00:11,835 the ones that defy medical treatment, 5 00:00:11,859 --> 00:00:14,375 even when we throw our best drugs at them. 6 00:00:15,247 --> 00:00:18,167 Engineering at the molecular level, 7 00:00:18,191 --> 00:00:20,839 working at the smallest of scales, 8 00:00:20,863 --> 00:00:23,386 can provide exciting new ways 9 00:00:23,410 --> 00:00:26,338 to fight the most aggressive forms of cancer. 10 00:00:27,260 --> 00:00:29,737 Cancer is a very clever disease. 11 00:00:30,346 --> 00:00:31,923 There are some forms of cancer, 12 00:00:31,947 --> 00:00:36,682 which, fortunately, we've learned how to address relatively well 13 00:00:36,706 --> 00:00:40,098 with known and established drugs and surgery. 14 00:00:40,627 --> 00:00:42,604 But there are some forms of cancer 15 00:00:42,628 --> 00:00:44,860 that don't respond to these approaches, 16 00:00:44,884 --> 00:00:47,512 and the tumor survives or comes back, 17 00:00:47,536 --> 00:00:49,665 even after an onslaught of drugs. 18 00:00:50,053 --> 00:00:54,047 We can think of these very aggressive forms of cancer 19 00:00:54,071 --> 00:00:56,937 as kind of supervillains in a comic book. 20 00:00:57,455 --> 00:01:00,160 They're clever, they're adaptable, 21 00:01:00,184 --> 00:01:02,993 and they're very good at staying alive. 22 00:01:03,744 --> 00:01:06,406 And, like most supervillains these days, 23 00:01:06,996 --> 00:01:10,906 their superpowers come from a genetic mutation. 24 00:01:12,740 --> 00:01:15,682 The genes that are modified inside these tumor cells 25 00:01:15,706 --> 00:01:20,973 can enable and encode for new and unimagined modes of survival, 26 00:01:20,997 --> 00:01:23,472 allowing the cancer cell to live through 27 00:01:23,496 --> 00:01:25,861 even our best chemotherapy treatments. 28 00:01:26,789 --> 00:01:31,296 One example is a trick in which a gene allows a cell, 29 00:01:31,320 --> 00:01:33,804 even as the drug approaches the cell, 30 00:01:34,390 --> 00:01:37,039 to push the drug out, 31 00:01:37,850 --> 00:01:40,023 before the drug can have any effect. 32 00:01:40,047 --> 00:01:43,733 Imagine -- the cell effectively spits out the drug. 33 00:01:44,393 --> 00:01:47,323 This is just one example of the many genetic tricks 34 00:01:47,347 --> 00:01:49,947 in the bag of our supervillain, cancer. 35 00:01:49,971 --> 00:01:52,131 All due to mutant genes. 36 00:01:52,717 --> 00:01:57,438 So, we have a supervillain with incredible superpowers. 37 00:01:57,462 --> 00:02:00,584 And we need a new and powerful mode of attack. 38 00:02:01,704 --> 00:02:04,788 Actually, we can turn off a gene. 39 00:02:05,328 --> 00:02:08,669 The key is a set of molecules known as siRNA. 40 00:02:09,143 --> 00:02:12,746 siRNA are short sequences of genetic code 41 00:02:13,253 --> 00:02:16,334 that guide a cell to block a certain gene. 42 00:02:16,982 --> 00:02:20,557 Each siRNA molecule can turn off a specific gene 43 00:02:20,581 --> 00:02:22,151 inside the cell. 44 00:02:23,292 --> 00:02:25,313 For many years since its discovery, 45 00:02:25,337 --> 00:02:27,287 scientists have been very excited 46 00:02:27,311 --> 00:02:30,668 about how we can apply these gene blockers in medicine. 47 00:02:31,216 --> 00:02:32,934 But, there is a problem. 48 00:02:32,958 --> 00:02:35,418 siRNA works well inside the cell. 49 00:02:35,854 --> 00:02:38,848 But if it gets exposed to the enzymes 50 00:02:38,872 --> 00:02:41,372 that reside in our bloodstream or our tissues, 51 00:02:41,396 --> 00:02:43,251 it degrades within seconds. 52 00:02:43,769 --> 00:02:48,085 It has to be packaged, protected through its journey through the body 53 00:02:48,109 --> 00:02:51,179 on its way to the final target inside the cancer cell. 54 00:02:51,740 --> 00:02:54,057 So, here's our strategy. 55 00:02:54,468 --> 00:02:58,271 First, we'll dose the cancer cell with siRNA, the gene blocker, 56 00:02:58,295 --> 00:02:59,891 and silence those survival genes, 57 00:02:59,915 --> 00:03:02,003 and then we'll whop it with a chemo drug. 58 00:03:02,501 --> 00:03:04,179 But how do we carry that out? 59 00:03:04,764 --> 00:03:06,544 Using molecular engineering, 60 00:03:07,705 --> 00:03:10,893 we can actually design a superweapon 61 00:03:11,648 --> 00:03:13,899 that can travel through the bloodstream. 62 00:03:13,923 --> 00:03:16,919 It has to be tiny enough to get through the bloodstream, 63 00:03:16,943 --> 00:03:19,814 it's got to be small enough to penetrate the tumor tissue, 64 00:03:20,368 --> 00:03:24,513 and it's got to be tiny enough to be taken up inside the cancer cell. 65 00:03:25,049 --> 00:03:26,651 To do this job well, 66 00:03:26,675 --> 00:03:31,480 it has to be about one one-hundredth the size of a human hair. 67 00:03:32,224 --> 00:03:35,605 Let's take a closer look at how we can build this nanoparticle. 68 00:03:37,146 --> 00:03:39,543 First, let's start with the nanoparticle core. 69 00:03:39,567 --> 00:03:43,367 It's a tiny capsule that contains the chemotherapy drug. 70 00:03:44,089 --> 00:03:47,566 This is the poison that will actually end the tumor cell's life. 71 00:03:48,152 --> 00:03:51,937 Around this core, we'll wrap a very thin, 72 00:03:51,961 --> 00:03:54,794 nanometers-thin blanket of siRNA. 73 00:03:54,818 --> 00:03:56,452 This is our gene blocker. 74 00:03:57,093 --> 00:04:00,682 Because siRNA is strongly negatively charged, 75 00:04:00,706 --> 00:04:02,263 we can protect it 76 00:04:02,287 --> 00:04:07,012 with a nice, protective layer of positively charged polymer. 77 00:04:07,503 --> 00:04:10,760 The two oppositely charged molecules stick together 78 00:04:10,784 --> 00:04:12,220 through charge attraction, 79 00:04:12,244 --> 00:04:14,378 and that provides us with a protective layer 80 00:04:14,402 --> 00:04:17,453 that prevents the siRNA from degrading in the bloodstream. 81 00:04:18,106 --> 00:04:19,406 We're almost done. 82 00:04:19,430 --> 00:04:20,890 (Laughter) 83 00:04:20,914 --> 00:04:24,992 But there is one more big obstacle we have to think about. 84 00:04:25,016 --> 00:04:27,408 In fact, it may be the biggest obstacle of all. 85 00:04:27,432 --> 00:04:29,406 How do we deploy this superweapon? 86 00:04:29,430 --> 00:04:31,984 I mean, every good weapon needs to be targeted, 87 00:04:32,008 --> 00:04:36,073 we have to target this superweapon to the supervillain cells 88 00:04:36,097 --> 00:04:38,047 that reside in the tumor. 89 00:04:38,071 --> 00:04:41,344 But our bodies have a natural immune-defense system: 90 00:04:41,916 --> 00:04:43,867 cells that reside in the bloodstream 91 00:04:43,891 --> 00:04:46,236 and pick out things that don't belong, 92 00:04:46,260 --> 00:04:48,559 so that it can destroy or eliminate them. 93 00:04:48,583 --> 00:04:53,019 And guess what? Our nanoparticle is considered a foreign object. 94 00:04:53,718 --> 00:04:57,817 We have to sneak our nanoparticle past the tumor defense system. 95 00:04:57,841 --> 00:05:04,095 We have to get it past this mechanism of getting rid of the foreign object 96 00:05:04,119 --> 00:05:05,539 by disguising it. 97 00:05:05,563 --> 00:05:09,908 So we add one more negatively charged layer 98 00:05:09,932 --> 00:05:11,256 around this nanoparticle, 99 00:05:11,280 --> 00:05:12,718 which serves two purposes. 100 00:05:13,140 --> 00:05:17,108 First, this outer layer is one of the naturally charged, 101 00:05:17,132 --> 00:05:20,845 highly hydrated polysaccharides that resides in our body. 102 00:05:21,456 --> 00:05:26,289 It creates a cloud of water molecules around the nanoparticle 103 00:05:26,313 --> 00:05:29,384 that gives us an invisibility cloaking effect. 104 00:05:30,257 --> 00:05:32,974 This invisibility cloak allows the nanoparticle 105 00:05:32,998 --> 00:05:34,604 to travel through the bloodstream 106 00:05:34,628 --> 00:05:37,393 long and far enough to reach the tumor, 107 00:05:37,417 --> 00:05:39,556 without getting eliminated by the body. 108 00:05:40,121 --> 00:05:44,513 Second, this layer contains molecules 109 00:05:44,537 --> 00:05:47,736 which bind specifically to our tumor cell. 110 00:05:48,190 --> 00:05:52,710 Once bound, the cancer cell takes up the nanoparticle, 111 00:05:52,734 --> 00:05:57,108 and now we have our nanoparticle inside the cancer cell 112 00:05:57,132 --> 00:05:58,805 and ready to deploy. 113 00:05:59,304 --> 00:06:01,541 Alright! I feel the same way. Let's go! 114 00:06:01,565 --> 00:06:07,747 (Applause) 115 00:06:08,057 --> 00:06:11,283 The siRNA is deployed first. 116 00:06:12,287 --> 00:06:13,913 It acts for hours, 117 00:06:13,937 --> 00:06:18,505 giving enough time to silence and block those survival genes. 118 00:06:19,398 --> 00:06:23,336 We have now disabled those genetic superpowers. 119 00:06:23,725 --> 00:06:26,954 What remains is a cancer cell with no special defenses. 120 00:06:26,978 --> 00:06:29,880 Then, the chemotherapy drug comes out of the core 121 00:06:29,904 --> 00:06:33,488 and destroys the tumor cell cleanly and efficiently. 122 00:06:34,228 --> 00:06:36,565 With sufficient gene blockers, 123 00:06:36,589 --> 00:06:39,799 we can address many different kinds of mutations, 124 00:06:39,823 --> 00:06:42,184 allowing the chance to sweep out tumors, 125 00:06:42,208 --> 00:06:44,399 without leaving behind any bad guys. 126 00:06:44,811 --> 00:06:47,527 So, how does our strategy work? 127 00:06:49,543 --> 00:06:53,504 We've tested these nanostructure particles in animals 128 00:06:53,528 --> 00:06:57,111 using a highly aggressive form of triple-negative breast cancer. 129 00:06:57,135 --> 00:06:59,690 This triple-negative breast cancer exhibits the gene 130 00:06:59,714 --> 00:07:03,189 that spits out cancer drug as soon as it is delivered. 131 00:07:03,742 --> 00:07:08,913 Usually, doxorubicin -- let's call it "dox" -- is the cancer drug 132 00:07:08,937 --> 00:07:11,746 that is the first line of treatment for breast cancer. 133 00:07:12,178 --> 00:07:17,948 So, we first treated our animals with a dox core, dox only. 134 00:07:18,661 --> 00:07:20,868 The tumor slowed their rate of growth, 135 00:07:20,892 --> 00:07:22,332 but they still grew rapidly, 136 00:07:22,356 --> 00:07:24,684 doubling in size over a period of two weeks. 137 00:07:25,297 --> 00:07:28,395 Then, we tried our combination superweapon. 138 00:07:29,415 --> 00:07:33,827 A nanolayer particle with siRNA against the chemo pump, 139 00:07:33,851 --> 00:07:36,846 plus, we have the dox in the core. 140 00:07:36,870 --> 00:07:41,185 And look -- we found that not only did the tumors stop growing, 141 00:07:41,209 --> 00:07:43,725 they actually decreased in size 142 00:07:43,749 --> 00:07:46,164 and were eliminated in some cases. 143 00:07:46,188 --> 00:07:49,444 The tumors were actually regressing. 144 00:07:49,859 --> 00:07:56,841 (Applause) 145 00:07:57,820 --> 00:08:01,628 What's great about this approach is that it can be personalized. 146 00:08:01,652 --> 00:08:04,488 We can add many different layers of siRNA 147 00:08:04,512 --> 00:08:08,070 to address different mutations and tumor defense mechanisms. 148 00:08:08,094 --> 00:08:11,379 And we can put different drugs into the nanoparticle core. 149 00:08:11,946 --> 00:08:15,153 As doctors learn how to test patients 150 00:08:15,177 --> 00:08:18,951 and understand certain tumor genetic types, 151 00:08:18,975 --> 00:08:22,717 they can help us determine which patients can benefit from this strategy 152 00:08:22,741 --> 00:08:25,019 and which gene blockers we can use. 153 00:08:26,410 --> 00:08:29,313 Ovarian cancer strikes a special chord with me. 154 00:08:29,337 --> 00:08:31,310 It is a very aggressive cancer, 155 00:08:31,334 --> 00:08:34,219 in part because it's discovered at very late stages, 156 00:08:34,243 --> 00:08:35,690 when it's highly advanced 157 00:08:35,714 --> 00:08:37,990 and there are a number of genetic mutations. 158 00:08:38,566 --> 00:08:41,555 After the first round of chemotherapy, 159 00:08:41,579 --> 00:08:45,969 this cancer comes back for 75 percent of patients. 160 00:08:46,333 --> 00:08:49,159 And it usually comes back in a drug-resistant form. 161 00:08:50,215 --> 00:08:51,909 High-grade ovarian cancer 162 00:08:51,933 --> 00:08:54,100 is one of the biggest supervillains out there. 163 00:08:54,124 --> 00:08:56,036 And we're now directing our superweapon 164 00:08:56,060 --> 00:08:57,376 toward its defeat. 165 00:08:59,375 --> 00:09:00,637 As a researcher, 166 00:09:00,661 --> 00:09:03,516 I usually don't get to work with patients. 167 00:09:04,164 --> 00:09:06,581 But I recently met a mother 168 00:09:06,605 --> 00:09:11,502 who is an ovarian cancer survivor, Mimi, and her daughter, Paige. 169 00:09:12,257 --> 00:09:16,361 I was deeply inspired by the optimism and strength 170 00:09:16,385 --> 00:09:18,478 that both mother and daughter displayed 171 00:09:19,495 --> 00:09:22,187 and by their story of courage and support. 172 00:09:23,119 --> 00:09:26,522 At this event, we spoke about the different technologies 173 00:09:26,546 --> 00:09:27,925 directed at cancer. 174 00:09:28,355 --> 00:09:29,664 And Mimi was in tears 175 00:09:29,688 --> 00:09:32,515 as she explained how learning about these efforts 176 00:09:32,539 --> 00:09:34,749 gives her hope for future generations, 177 00:09:34,773 --> 00:09:36,658 including her own daughter. 178 00:09:37,449 --> 00:09:38,863 This really touched me. 179 00:09:39,524 --> 00:09:42,703 It's not just about building really elegant science. 180 00:09:43,140 --> 00:09:45,239 It's about changing people's lives. 181 00:09:46,330 --> 00:09:49,541 It's about understanding the power of engineering 182 00:09:49,565 --> 00:09:51,446 on the scale of molecules. 183 00:09:51,470 --> 00:09:55,553 I know that as students like Paige move forward in their careers, 184 00:09:55,577 --> 00:09:57,017 they'll open new possibilities 185 00:09:57,041 --> 00:10:00,431 in addressing some of the big health problems in the world -- 186 00:10:00,455 --> 00:10:05,454 including ovarian cancer, neurological disorders, infectious disease -- 187 00:10:06,104 --> 00:10:10,045 just as chemical engineering has found a way to open doors for me, 188 00:10:10,437 --> 00:10:13,071 and has provided a way of engineering 189 00:10:13,095 --> 00:10:16,627 on the tiniest scale, that of molecules, 190 00:10:16,651 --> 00:10:19,214 to heal on the human scale. 191 00:10:19,797 --> 00:10:20,955 Thank you. 192 00:10:20,979 --> 00:10:29,539 (Applause)