1 00:00:00,997 --> 00:00:03,203 Cancer affects all of us, 2 00:00:03,203 --> 00:00:06,523 especially the ones that come back over and over again. 3 00:00:06,523 --> 00:00:09,542 The highly invasive and drug-resistant ones, 4 00:00:09,542 --> 00:00:11,910 the ones that defy medical treatment, 5 00:00:11,910 --> 00:00:15,440 even when we throw our best drugs at them. 6 00:00:15,440 --> 00:00:18,365 Engineering at the molecular level, 7 00:00:18,365 --> 00:00:21,036 working at the smallest of scales, 8 00:00:21,036 --> 00:00:23,497 can provide exciting new ways 9 00:00:23,497 --> 00:00:27,491 to fight the most aggressive forms of cancer. 10 00:00:27,491 --> 00:00:29,992 Cancer is a very clever disease. 11 00:00:29,992 --> 00:00:32,042 There are some forms of cancer, 12 00:00:32,042 --> 00:00:36,941 which, fortunately, we've learned how to address relatively well 13 00:00:36,941 --> 00:00:40,842 with known and established drugs and surgery. 14 00:00:40,842 --> 00:00:43,388 But, there's some forms of cancer that don't respond 15 00:00:43,388 --> 00:00:45,115 to these approaches 16 00:00:45,115 --> 00:00:47,715 and the tumor survives or comes back, 17 00:00:47,715 --> 00:00:50,316 even after an onslaught of drugs. 18 00:00:50,316 --> 00:00:54,333 We can think of these very aggresive forms of cancer 19 00:00:54,333 --> 00:00:57,677 as kind of super villains in a comic book. 20 00:00:57,677 --> 00:01:00,475 They're clever, they're adaptable, 21 00:01:00,475 --> 00:01:04,062 and they're very good at staying alive. 22 00:01:04,062 --> 00:01:07,290 And, like most super villains these days, 23 00:01:07,290 --> 00:01:12,979 their super powers come from a genetic mutation. 24 00:01:12,979 --> 00:01:15,881 The genes that are modified inside these tumor cells 25 00:01:15,881 --> 00:01:21,222 can enable and encode for new and unimagined modes of survival, 26 00:01:21,222 --> 00:01:23,637 allowing the cancer cell to live through 27 00:01:23,637 --> 00:01:27,004 even our best chemotherapy treatments. 28 00:01:27,004 --> 00:01:31,534 One example is a trick in which a gene allows a cell, 29 00:01:31,534 --> 00:01:34,597 even as the drug approaches the cell, 30 00:01:34,597 --> 00:01:40,309 to push the drug out before the drug can have any effect. 31 00:01:40,309 --> 00:01:44,604 Imagine the cell effectively spits out the drug. 32 00:01:44,604 --> 00:01:47,577 This is just one example of the many genetic tricks 33 00:01:47,577 --> 00:01:50,200 in the bag of our super villain, cancer. 34 00:01:50,200 --> 00:01:53,103 All due to mutant genes. 35 00:01:53,103 --> 00:01:57,724 So, we have a super villain with incredible super powers 36 00:01:57,724 --> 00:02:01,903 and we need a new and powerful mode of attack. 37 00:02:01,903 --> 00:02:05,526 Actually, we can turn off a gene, 38 00:02:05,526 --> 00:02:09,380 the key is a set of molecules known as siRNA. 39 00:02:09,380 --> 00:02:13,420 siRNA are short sequences of genetic code 40 00:02:13,420 --> 00:02:17,205 that guide a cell to block a certain gene. 41 00:02:17,205 --> 00:02:20,582 Each siRNA molecule can turn off a specific gene 42 00:02:20,582 --> 00:02:23,451 inside the cell. 43 00:02:23,451 --> 00:02:25,495 For many years since its discovery, 44 00:02:25,495 --> 00:02:27,468 scientists have been very excited 45 00:02:27,468 --> 00:02:31,439 about how we can apply these gene blockers in medicine. 46 00:02:31,439 --> 00:02:33,180 But, there is a problem. 47 00:02:33,180 --> 00:02:36,037 siRNA works well inside the cell. 48 00:02:36,037 --> 00:02:39,496 But if it gets exposed to the enzymes that reside 49 00:02:39,496 --> 00:02:41,540 in our bloodstream or our tissues, 50 00:02:41,540 --> 00:02:43,769 it degrades within seconds. 51 00:02:43,769 --> 00:02:48,320 It has to be packaged, protected through its journey through the body 52 00:02:48,320 --> 00:02:52,082 on its way to the final target inside the cancer cell. 53 00:02:52,082 --> 00:02:54,659 So, here's our strategy: 54 00:02:54,659 --> 00:02:58,123 first, we'll dose the cancer cell with siRNA, the gene blocker, 55 00:02:58,123 --> 00:03:00,046 and silence those survival genes, 56 00:03:00,046 --> 00:03:02,716 and they'll we'll whap it with a chemo drug. 57 00:03:02,716 --> 00:03:04,876 But how do we carry that out? 58 00:03:04,876 --> 00:03:07,825 Using molecular engineering, 59 00:03:07,825 --> 00:03:11,911 we can actually design a super weapon 60 00:03:11,911 --> 00:03:13,924 that can travel through the blood stream. 61 00:03:13,924 --> 00:03:17,066 It has to be tiny enough that it can get through the blood stream, 62 00:03:17,066 --> 00:03:20,805 it's got to be small enough to penetrate the tumor tissue, 63 00:03:20,805 --> 00:03:23,080 and it's got to be tiny enough to be taken up 64 00:03:23,080 --> 00:03:25,240 inside the cancer cell. 65 00:03:25,240 --> 00:03:30,464 To do this job well, it has to be about one 100th the size 66 00:03:30,464 --> 00:03:32,438 of a human hair. 67 00:03:32,438 --> 00:03:37,337 Let's take a closer look at how we can build this nanoparticle. 68 00:03:37,337 --> 00:03:39,799 First, let's start with the nanoparticle core. 69 00:03:39,799 --> 00:03:44,326 It's a tiny capsule that contains the chemotherapy drug. 70 00:03:44,326 --> 00:03:48,390 This is the poison that will actually end the tumor cell's life. 71 00:03:48,390 --> 00:03:52,198 Around this core, we'll wrap a very thin, 72 00:03:52,198 --> 00:03:55,054 nanometers-thin blanket of siRNA. 73 00:03:55,054 --> 00:03:57,093 This is our gene blocker. 74 00:03:57,093 --> 00:04:00,446 Because siRNA is strongly negatively charged, 75 00:04:00,446 --> 00:04:04,966 we can protect it with a nice protect layer 76 00:04:04,966 --> 00:04:07,662 of postively charged polymer. 77 00:04:07,662 --> 00:04:09,736 The two oppositely charged molecules 78 00:04:09,736 --> 00:04:12,446 stick together through charge attraction 79 00:04:12,446 --> 00:04:14,986 and that provides us with a protective layer 80 00:04:14,986 --> 00:04:18,297 that prevents the siRNA from degrading in the blood stream. 81 00:04:18,297 --> 00:04:19,946 We're almost done. 82 00:04:19,946 --> 00:04:21,269 (Laughter) 83 00:04:21,269 --> 00:04:25,240 But there is one more big obstacle we have to think about. 84 00:04:25,240 --> 00:04:27,655 In fact, it may be the biggest obstacle of all. 85 00:04:27,655 --> 00:04:29,652 How do we deploy this super weapon? 86 00:04:29,652 --> 00:04:32,229 I mean, every good weapon needs to be targeted, 87 00:04:32,229 --> 00:04:36,293 we have to target this super weapon to the super villain cells 88 00:04:36,293 --> 00:04:38,266 that reside in the tumor. 89 00:04:38,266 --> 00:04:42,028 But, our bodies have a natural immune defense system. 90 00:04:42,028 --> 00:04:44,002 Cells that reside in the blood stream 91 00:04:44,002 --> 00:04:46,579 and pick out things that don't belong 92 00:04:46,579 --> 00:04:48,901 so that it can destroy or elinate them. 93 00:04:48,901 --> 00:04:53,893 And guess that, our nanoparticle is considered a foreign object. 94 00:04:53,893 --> 00:04:55,797 We have to sneak our nanoparticle 95 00:04:55,797 --> 00:04:57,841 past the tumor defense system, 96 00:04:57,841 --> 00:05:04,389 we have to get it past this mechanism of getting rid of the foreign object 97 00:05:04,389 --> 00:05:06,037 by disguising it. 98 00:05:06,037 --> 00:05:10,194 So we add one more negatively charged layer 99 00:05:10,194 --> 00:05:11,541 around this nanoparticle, 100 00:05:11,541 --> 00:05:13,003 which serves two purposes. 101 00:05:13,003 --> 00:05:17,253 First, this outer layer is one of the naturally charged, 102 00:05:17,253 --> 00:05:21,456 highly hydrated polysaccarides that resides in our bodies. 103 00:05:21,456 --> 00:05:26,448 It creates a cloud of water molecules around the nanoparticle 104 00:05:26,448 --> 00:05:30,511 that gives us an invisibility cloaking affect. 105 00:05:30,511 --> 00:05:33,251 This invisibility cloak allows the nanoparticle 106 00:05:33,251 --> 00:05:36,084 to travel through the bloodstream long and far enough 107 00:05:36,084 --> 00:05:39,730 to reach the tumor without getting eliminated by the body. 108 00:05:39,730 --> 00:05:46,115 Second, this layer contains molecules which bind specifically 109 00:05:46,115 --> 00:05:48,437 to our tumor's cell. 110 00:05:48,437 --> 00:05:51,830 Once bound, the cancer cell takes up the nanoparticle 111 00:05:51,830 --> 00:05:57,354 and now we have our nanoparticle inside the cancer cell 112 00:05:57,354 --> 00:05:59,559 and ready to deploy. 113 00:05:59,559 --> 00:06:02,186 Alright, I feel the same way, let's go. 114 00:06:02,186 --> 00:06:04,754 (Applause) 115 00:06:07,824 --> 00:06:12,493 The siRNA is deployed first. 116 00:06:12,493 --> 00:06:14,142 It acts for hours, 117 00:06:14,142 --> 00:06:19,668 giving enough time to silence and block those survival genes. 118 00:06:19,668 --> 00:06:23,964 We have now disabled those genetic superpowers. 119 00:06:23,964 --> 00:06:27,145 What remains is a cancer cell with no special defenses. 120 00:06:27,145 --> 00:06:30,070 Then, the chemotherapy drug comes out of the core 121 00:06:30,070 --> 00:06:34,482 and destroys the tumor cell cleanly and efficiently. 122 00:06:34,482 --> 00:06:36,804 With sufficient gene blockers, 123 00:06:36,804 --> 00:06:39,823 we can address many different kinds of mutations. 124 00:06:39,823 --> 00:06:45,024 Allowing the chance to sweep out tumors, without leaving behind any bad guys. 125 00:06:45,024 --> 00:06:48,511 So, how does our strategy work? 126 00:06:48,511 --> 00:06:53,755 We've tested these nanostructure particles in animals 127 00:06:53,755 --> 00:06:57,516 using a highly aggresive form of triple negative breast cancer. 128 00:06:57,516 --> 00:07:00,094 This triple negative breast cancer exhibits the gene 129 00:07:00,094 --> 00:07:03,925 that spits out cancer drugs as soon as its delivered. 130 00:07:03,925 --> 00:07:08,012 Usually, doxorubicin, let's call it dox, 131 00:07:08,012 --> 00:07:10,798 is the cancer drug that is the first line of treatment 132 00:07:10,798 --> 00:07:12,540 for breast cancer. 133 00:07:12,540 --> 00:07:18,972 So, we first treated our animals with a dox core, dox only. 134 00:07:18,972 --> 00:07:21,131 The tumor slowed their rate of growth, 135 00:07:21,131 --> 00:07:22,594 but they still grew rapidly, 136 00:07:22,594 --> 00:07:24,946 doubling in size over a period of two weeks. 137 00:07:24,946 --> 00:07:29,653 Then, we tried our combination super weapon. 138 00:07:29,653 --> 00:07:34,088 And now layer a particle with siRNA against the chemo pump, 139 00:07:34,088 --> 00:07:37,106 plus, we have the dox in the core. 140 00:07:37,106 --> 00:07:41,565 And look, we found that not only did the tumors stop growing, 141 00:07:41,565 --> 00:07:43,956 they actually decerased in size 142 00:07:43,956 --> 00:07:46,394 and were elimintaed in some cases. 143 00:07:46,394 --> 00:07:49,970 The tumors were actually regressing. 144 00:07:49,970 --> 00:07:52,804 (Applause) 145 00:07:58,074 --> 00:08:01,905 What's great about this approach is that it can be personalized, 146 00:08:01,905 --> 00:08:04,576 we can add many different layers of siRNA 147 00:08:04,576 --> 00:08:08,198 to address different mutations and tumor defense mechanisms 148 00:08:08,198 --> 00:08:12,169 and we can put different drugs into the nanoparticle core. 149 00:08:12,169 --> 00:08:15,504 As doctors learn how to test patients 150 00:08:15,504 --> 00:08:19,158 and understand certain tumor genetic types, 151 00:08:19,158 --> 00:08:21,294 they can help us determine which patients 152 00:08:21,294 --> 00:08:22,873 can benefit from this strategy 153 00:08:22,873 --> 00:08:26,704 and which gene blockers we can use. 154 00:08:26,704 --> 00:08:29,584 Ovarian cancer strikes a special chord with me. 155 00:08:29,584 --> 00:08:31,580 It is a very aggresive cancer, 156 00:08:31,580 --> 00:08:34,320 in part because it's discovered at very late stages 157 00:08:34,320 --> 00:08:35,853 when its highly advanced 158 00:08:35,853 --> 00:08:38,709 and there are a number of genetic mutations. 159 00:08:38,709 --> 00:08:41,797 After the first round of chemotherapy, 160 00:08:41,797 --> 00:08:46,604 this cancer comes back for 75 percent of patients. 161 00:08:46,604 --> 00:08:49,918 And it usually comes back in a drug resistant form. 162 00:08:49,918 --> 00:08:52,149 High-grade ovarian cancer 163 00:08:52,149 --> 00:08:54,416 is one of the biggest super villains out there. 164 00:08:54,416 --> 00:08:56,424 And we're now directlng our super weapon 165 00:08:56,424 --> 00:08:59,653 towards its defeat. 166 00:08:59,653 --> 00:09:00,907 As a researcher, 167 00:09:00,907 --> 00:09:04,205 I usually don't get to work with patients. 168 00:09:04,205 --> 00:09:06,782 But I recently met a mother 169 00:09:06,782 --> 00:09:12,401 who is an ovarian cancer survivor, Mimi, and her daughter Paige. 170 00:09:12,401 --> 00:09:14,375 I was deeply inspired 171 00:09:14,375 --> 00:09:16,488 by the optimism and strength 172 00:09:16,488 --> 00:09:19,646 that both mother and daughter displayed 173 00:09:19,646 --> 00:09:23,175 and by their story of courage and support. 174 00:09:23,175 --> 00:09:26,658 At this event, we spoke about the different technologies 175 00:09:26,658 --> 00:09:28,609 directed at cancer. 176 00:09:28,609 --> 00:09:30,861 And Mimi was in tears as she explained how 177 00:09:30,861 --> 00:09:32,719 learning about these efforts 178 00:09:32,719 --> 00:09:34,901 gives her hope for future generations, 179 00:09:34,901 --> 00:09:37,711 including her own daughter. 180 00:09:37,711 --> 00:09:39,731 This really touched me. 181 00:09:39,731 --> 00:09:43,307 It's not just about building really elegant science, 182 00:09:43,307 --> 00:09:46,558 it's about changing people's lives. 183 00:09:46,558 --> 00:09:49,716 It's about understanding the power of engineering 184 00:09:49,716 --> 00:09:51,620 on the scale of molecules. 185 00:09:51,620 --> 00:09:53,709 I know that as students like Paige 186 00:09:53,709 --> 00:09:55,776 move forward in their careers, 187 00:09:55,776 --> 00:09:57,239 they'll open new possibilites 188 00:09:57,239 --> 00:10:00,652 in addressing some of the big health problems in the world, 189 00:10:00,652 --> 00:10:04,042 including, ovarian cancer, neurological disorders, 190 00:10:04,042 --> 00:10:06,248 infectious disease. 191 00:10:06,248 --> 00:10:08,733 Just as chemical engineering has found a way 192 00:10:08,733 --> 00:10:10,660 to open doors for me. 193 00:10:10,660 --> 00:10:15,258 Has provided a way of engineering on the tiniest scale, 194 00:10:15,258 --> 00:10:16,860 that of molecules 195 00:10:16,860 --> 00:10:19,971 to heal on the human scale. 196 00:10:19,971 --> 00:10:21,063 Thank you 197 00:10:21,063 --> 00:10:24,085 (Applause)