WEBVTT 00:00:00.997 --> 00:00:03.203 Cancer affects all of us, 00:00:03.203 --> 00:00:06.523 especially the ones that come back over and over again. 00:00:06.523 --> 00:00:09.542 The highly invasive and drug-resistant ones, 00:00:09.542 --> 00:00:11.910 the ones that defy medical treatment, 00:00:11.910 --> 00:00:15.440 even when we throw our best drugs at them. 00:00:15.440 --> 00:00:18.365 Engineering at the molecular level, 00:00:18.365 --> 00:00:21.036 working at the smallest of scales, 00:00:21.036 --> 00:00:23.497 can provide exciting new ways 00:00:23.497 --> 00:00:27.491 to fight the most aggressive forms of cancer. NOTE Paragraph 00:00:27.491 --> 00:00:29.992 Cancer is a very clever disease. 00:00:29.992 --> 00:00:32.042 There are some forms of cancer, 00:00:32.042 --> 00:00:36.941 which, fortunately, we've learned how to address relatively well 00:00:36.941 --> 00:00:40.842 with known and established drugs and surgery. 00:00:40.842 --> 00:00:43.388 But, there's some forms of cancer that don't respond 00:00:43.388 --> 00:00:45.115 to these approaches 00:00:45.115 --> 00:00:47.715 and the tumor survives or comes back, 00:00:47.715 --> 00:00:50.316 even after an onslaught of drugs. NOTE Paragraph 00:00:50.316 --> 00:00:54.333 We can think of these very aggresive forms of cancer 00:00:54.333 --> 00:00:57.677 as kind of super villains in a comic book. 00:00:57.677 --> 00:01:00.475 They're clever, they're adaptable, 00:01:00.475 --> 00:01:04.062 and they're very good at staying alive. 00:01:04.062 --> 00:01:07.290 And, like most super villains these days, 00:01:07.290 --> 00:01:12.979 their super powers come from a genetic mutation. 00:01:12.979 --> 00:01:15.881 The genes that are modified inside these tumor cells 00:01:15.881 --> 00:01:21.222 can enable and encode for new and unimagined modes of survival, 00:01:21.222 --> 00:01:23.637 allowing the cancer cell to live through 00:01:23.637 --> 00:01:27.004 even our best chemotherapy treatments. NOTE Paragraph 00:01:27.004 --> 00:01:31.534 One example is a trick in which a gene allows a cell, 00:01:31.534 --> 00:01:34.597 even as the drug approaches the cell, 00:01:34.597 --> 00:01:40.309 to push the drug out before the drug can have any effect. 00:01:40.309 --> 00:01:44.604 Imagine the cell effectively spits out the drug. 00:01:44.604 --> 00:01:47.577 This is just one example of the many genetic tricks 00:01:47.577 --> 00:01:50.200 in the bag of our super villain, cancer. 00:01:50.200 --> 00:01:53.103 All due to mutant genes. NOTE Paragraph 00:01:53.103 --> 00:01:57.724 So, we have a super villain with incredible super powers 00:01:57.724 --> 00:02:01.903 and we need a new and powerful mode of attack. 00:02:01.903 --> 00:02:05.526 Actually, we can turn off a gene, 00:02:05.526 --> 00:02:09.380 the key is a set of molecules known as siRNA. 00:02:09.380 --> 00:02:13.420 siRNA are short sequences of genetic code 00:02:13.420 --> 00:02:17.205 that guide a cell to block a certain gene. 00:02:17.205 --> 00:02:20.582 Each siRNA molecule can turn off a specific gene 00:02:20.582 --> 00:02:23.451 inside the cell. 00:02:23.451 --> 00:02:25.495 For many years since its discovery, 00:02:25.495 --> 00:02:27.468 scientists have been very excited 00:02:27.468 --> 00:02:31.439 about how we can apply these gene blockers in medicine. NOTE Paragraph 00:02:31.439 --> 00:02:33.180 But, there is a problem. 00:02:33.180 --> 00:02:36.037 siRNA works well inside the cell. 00:02:36.037 --> 00:02:39.496 But if it gets exposed to the enzymes that reside 00:02:39.496 --> 00:02:41.540 in our bloodstream or our tissues, 00:02:41.540 --> 00:02:43.769 it degrades within seconds. 00:02:43.769 --> 00:02:48.320 It has to be packaged, protected through its journey through the body 00:02:48.320 --> 00:02:52.082 on its way to the final target inside the cancer cell. NOTE Paragraph 00:02:52.082 --> 00:02:54.659 So, here's our strategy: 00:02:54.659 --> 00:02:58.123 first, we'll dose the cancer cell with siRNA, the gene blocker, 00:02:58.123 --> 00:03:00.046 and silence those survival genes, 00:03:00.046 --> 00:03:02.716 and they'll we'll whap it with a chemo drug. NOTE Paragraph 00:03:02.716 --> 00:03:04.876 But how do we carry that out? 00:03:04.876 --> 00:03:07.825 Using molecular engineering, 00:03:07.825 --> 00:03:11.911 we can actually design a super weapon 00:03:11.911 --> 00:03:13.924 that can travel through the blood stream. 00:03:13.924 --> 00:03:17.066 It has to be tiny enough that it can get through the blood stream, 00:03:17.066 --> 00:03:20.805 it's got to be small enough to penetrate the tumor tissue, 00:03:20.805 --> 00:03:23.080 and it's got to be tiny enough to be taken up 00:03:23.080 --> 00:03:25.240 inside the cancer cell. 00:03:25.240 --> 00:03:30.464 To do this job well, it has to be about one 100th the size 00:03:30.464 --> 00:03:32.438 of a human hair. NOTE Paragraph 00:03:32.438 --> 00:03:37.337 Let's take a closer look at how we can build this nanoparticle. 00:03:37.337 --> 00:03:39.799 First, let's start with the nanoparticle core. 00:03:39.799 --> 00:03:44.326 It's a tiny capsule that contains the chemotherapy drug. 00:03:44.326 --> 00:03:48.390 This is the poison that will actually end the tumor cell's life. 00:03:48.390 --> 00:03:52.198 Around this core, we'll wrap a very thin, 00:03:52.198 --> 00:03:55.054 nanometers-thin blanket of siRNA. 00:03:55.054 --> 00:03:57.093 This is our gene blocker. 00:03:57.093 --> 00:04:00.446 Because siRNA is strongly negatively charged, 00:04:00.446 --> 00:04:04.966 we can protect it with a nice protect layer 00:04:04.966 --> 00:04:07.662 of postively charged polymer. 00:04:07.662 --> 00:04:09.736 The two oppositely charged molecules 00:04:09.736 --> 00:04:12.446 stick together through charge attraction 00:04:12.446 --> 00:04:14.986 and that provides us with a protective layer 00:04:14.986 --> 00:04:18.297 that prevents the siRNA from degrading in the blood stream. 00:04:18.297 --> 00:04:19.946 We're almost done. 00:04:19.946 --> 00:04:21.269 (Laughter) NOTE Paragraph 00:04:21.269 --> 00:04:25.240 But there is one more big obstacle we have to think about. 00:04:25.240 --> 00:04:27.655 In fact, it may be the biggest obstacle of all. 00:04:27.655 --> 00:04:29.652 How do we deploy this super weapon? 00:04:29.652 --> 00:04:32.229 I mean, every good weapon needs to be targeted, 00:04:32.229 --> 00:04:36.293 we have to target this super weapon to the super villain cells 00:04:36.293 --> 00:04:38.266 that reside in the tumor. NOTE Paragraph 00:04:38.266 --> 00:04:42.028 But, our bodies have a natural immune defense system. 00:04:42.028 --> 00:04:44.002 Cells that reside in the blood stream 00:04:44.002 --> 00:04:46.579 and pick out things that don't belong 00:04:46.579 --> 00:04:48.901 so that it can destroy or elinate them. 00:04:48.901 --> 00:04:53.893 And guess that, our nanoparticle is considered a foreign object. NOTE Paragraph 00:04:53.893 --> 00:04:55.797 We have to sneak our nanoparticle 00:04:55.797 --> 00:04:57.841 past the tumor defense system, 00:04:57.841 --> 00:05:04.389 we have to get it past this mechanism of getting rid of the foreign object 00:05:04.389 --> 00:05:06.037 by disguising it. NOTE Paragraph 00:05:06.037 --> 00:05:10.194 So we add one more negatively charged layer 00:05:10.194 --> 00:05:11.541 around this nanoparticle, 00:05:11.541 --> 00:05:13.003 which serves two purposes. 00:05:13.003 --> 00:05:17.253 First, this outer layer is one of the naturally charged, 00:05:17.253 --> 00:05:21.456 highly hydrated polysaccarides that resides in our bodies. 00:05:21.456 --> 00:05:26.448 It creates a cloud of water molecules around the nanoparticle 00:05:26.448 --> 00:05:30.511 that gives us an invisibility cloaking affect. 00:05:30.511 --> 00:05:33.251 This invisibility cloak allows the nanoparticle 00:05:33.251 --> 00:05:36.084 to travel through the bloodstream long and far enough 00:05:36.084 --> 00:05:39.730 to reach the tumor without getting eliminated by the body. NOTE Paragraph 00:05:39.730 --> 00:05:46.115 Second, this layer contains molecules which bind specifically 00:05:46.115 --> 00:05:48.437 to our tumor's cell. 00:05:48.437 --> 00:05:51.830 Once bound, the cancer cell takes up the nanoparticle 00:05:51.830 --> 00:05:57.354 and now we have our nanoparticle inside the cancer cell 00:05:57.354 --> 00:05:59.559 and ready to deploy. 00:05:59.559 --> 00:06:02.186 Alright, I feel the same way, let's go. 00:06:02.186 --> 00:06:04.754 (Applause) NOTE Paragraph 00:06:07.824 --> 00:06:12.493 The siRNA is deployed first. 00:06:12.493 --> 00:06:14.142 It acts for hours, 00:06:14.142 --> 00:06:19.668 giving enough time to silence and block those survival genes. 00:06:19.668 --> 00:06:23.964 We have now disabled those genetic superpowers. 00:06:23.964 --> 00:06:27.145 What remains is a cancer cell with no special defenses. 00:06:27.145 --> 00:06:30.070 Then, the chemotherapy drug comes out of the core 00:06:30.070 --> 00:06:34.482 and destroys the tumor cell cleanly and efficiently. 00:06:34.482 --> 00:06:36.804 With sufficient gene blockers, 00:06:36.804 --> 00:06:39.823 we can address many different kinds of mutations. 00:06:39.823 --> 00:06:45.024 Allowing the chance to sweep out tumors, without leaving behind any bad guys. NOTE Paragraph 00:06:45.024 --> 00:06:48.511 So, how does our strategy work? 00:06:48.511 --> 00:06:53.755 We've tested these nanostructure particles in animals 00:06:53.755 --> 00:06:57.516 using a highly aggresive form of triple negative breast cancer. 00:06:57.516 --> 00:07:00.094 This triple negative breast cancer exhibits the gene 00:07:00.094 --> 00:07:03.925 that spits out cancer drugs as soon as its delivered. NOTE Paragraph 00:07:03.925 --> 00:07:08.012 Usually, doxorubicin, let's call it dox, 00:07:08.012 --> 00:07:10.798 is the cancer drug that is the first line of treatment 00:07:10.798 --> 00:07:12.540 for breast cancer. 00:07:12.540 --> 00:07:18.972 So, we first treated our animals with a dox core, dox only. 00:07:18.972 --> 00:07:21.131 The tumor slowed their rate of growth, 00:07:21.131 --> 00:07:22.594 but they still grew rapidly, 00:07:22.594 --> 00:07:24.946 doubling in size over a period of two weeks. NOTE Paragraph 00:07:24.946 --> 00:07:29.653 Then, we tried our combination super weapon. 00:07:29.653 --> 00:07:34.088 And now layer a particle with siRNA against the chemo pump, 00:07:34.088 --> 00:07:37.106 plus, we have the dox in the core. 00:07:37.106 --> 00:07:41.565 And look, we found that not only did the tumors stop growing, 00:07:41.565 --> 00:07:43.956 they actually decerased in size 00:07:43.956 --> 00:07:46.394 and were elimintaed in some cases. 00:07:46.394 --> 00:07:49.970 The tumors were actually regressing. 00:07:49.970 --> 00:07:52.804 (Applause) NOTE Paragraph 00:07:58.074 --> 00:08:01.905 What's great about this approach is that it can be personalized, 00:08:01.905 --> 00:08:04.576 we can add many different layers of siRNA 00:08:04.576 --> 00:08:08.198 to address different mutations and tumor defense mechanisms 00:08:08.198 --> 00:08:12.169 and we can put different drugs into the nanoparticle core. NOTE Paragraph 00:08:12.169 --> 00:08:15.504 As doctors learn how to test patients 00:08:15.504 --> 00:08:19.158 and understand certain tumor genetic types, 00:08:19.158 --> 00:08:21.294 they can help us determine which patients 00:08:21.294 --> 00:08:22.873 can benefit from this strategy 00:08:22.873 --> 00:08:26.704 and which gene blockers we can use. NOTE Paragraph 00:08:26.704 --> 00:08:29.584 Ovarian cancer strikes a special chord with me. 00:08:29.584 --> 00:08:31.580 It is a very aggresive cancer, 00:08:31.580 --> 00:08:34.320 in part because it's discovered at very late stages 00:08:34.320 --> 00:08:35.853 when its highly advanced 00:08:35.853 --> 00:08:38.709 and there are a number of genetic mutations. 00:08:38.709 --> 00:08:41.797 After the first round of chemotherapy, 00:08:41.797 --> 00:08:46.604 this cancer comes back for 75 percent of patients. 00:08:46.604 --> 00:08:49.918 And it usually comes back in a drug resistant form. 00:08:49.918 --> 00:08:52.149 High-grade ovarian cancer 00:08:52.149 --> 00:08:54.416 is one of the biggest super villains out there. 00:08:54.416 --> 00:08:56.424 And we're now directlng our super weapon 00:08:56.424 --> 00:08:59.653 towards its defeat. NOTE Paragraph 00:08:59.653 --> 00:09:00.907 As a researcher, 00:09:00.907 --> 00:09:04.205 I usually don't get to work with patients. 00:09:04.205 --> 00:09:06.782 But I recently met a mother 00:09:06.782 --> 00:09:12.401 who is an ovarian cancer survivor, Mimi, and her daughter Paige. 00:09:12.401 --> 00:09:14.375 I was deeply inspired 00:09:14.375 --> 00:09:16.488 by the optimism and strength 00:09:16.488 --> 00:09:19.646 that both mother and daughter displayed 00:09:19.646 --> 00:09:23.175 and by their story of courage and support. NOTE Paragraph 00:09:23.175 --> 00:09:26.658 At this event, we spoke about the different technologies 00:09:26.658 --> 00:09:28.609 directed at cancer. 00:09:28.609 --> 00:09:30.861 And Mimi was in tears as she explained how 00:09:30.861 --> 00:09:32.719 learning about these efforts 00:09:32.719 --> 00:09:34.901 gives her hope for future generations, 00:09:34.901 --> 00:09:37.711 including her own daughter. 00:09:37.711 --> 00:09:39.731 This really touched me. 00:09:39.731 --> 00:09:43.307 It's not just about building really elegant science, 00:09:43.307 --> 00:09:46.558 it's about changing people's lives. 00:09:46.558 --> 00:09:49.716 It's about understanding the power of engineering 00:09:49.716 --> 00:09:51.620 on the scale of molecules. NOTE Paragraph 00:09:51.620 --> 00:09:53.709 I know that as students like Paige 00:09:53.709 --> 00:09:55.776 move forward in their careers, 00:09:55.776 --> 00:09:57.239 they'll open new possibilites 00:09:57.239 --> 00:10:00.652 in addressing some of the big health problems in the world, 00:10:00.652 --> 00:10:04.042 including, ovarian cancer, neurological disorders, 00:10:04.042 --> 00:10:06.248 infectious disease. 00:10:06.248 --> 00:10:08.733 Just as chemical engineering has found a way 00:10:08.733 --> 00:10:10.660 to open doors for me. 00:10:10.660 --> 00:10:15.258 Has provided a way of engineering on the tiniest scale, 00:10:15.258 --> 00:10:16.860 that of molecules 00:10:16.860 --> 00:10:19.971 to heal on the human scale. NOTE Paragraph 00:10:19.971 --> 00:10:21.063 Thank you NOTE Paragraph 00:10:21.063 --> 00:10:24.085 (Applause)