WEBVTT 99:59:59.999 --> 99:59:59.999 Cancer affects all of us, 99:59:59.999 --> 99:59:59.999 especially the ones that come back over and over again. 99:59:59.999 --> 99:59:59.999 The highly invasive and drug-resistant ones, 99:59:59.999 --> 99:59:59.999 the ones that defy medical treatment, 99:59:59.999 --> 99:59:59.999 even when we throw our best drugs at them. 99:59:59.999 --> 99:59:59.999 Engineering at the molecular level, 99:59:59.999 --> 99:59:59.999 working at the smallest of scales, 99:59:59.999 --> 99:59:59.999 can provide exciting new ways 99:59:59.999 --> 99:59:59.999 to find the most aggressive forms of cancer. 99:59:59.999 --> 99:59:59.999 Cancer is a very clever disease. 99:59:59.999 --> 99:59:59.999 There are some forms of cancer, 99:59:59.999 --> 99:59:59.999 which, fortunately, we've learned how to address relatively well 99:59:59.999 --> 99:59:59.999 with known and established drugs and surgery. 99:59:59.999 --> 99:59:59.999 But, there's some forms of cancer that don't respond 99:59:59.999 --> 99:59:59.999 to these approaches 99:59:59.999 --> 99:59:59.999 and the tumor survives or comes back, 99:59:59.999 --> 99:59:59.999 even after an onslaught of drugs. 99:59:59.999 --> 99:59:59.999 We can think of these very aggresive forms of cancer 99:59:59.999 --> 99:59:59.999 as kind of super villains in a comic book. 99:59:59.999 --> 99:59:59.999 They're clever, they're adaptable, 99:59:59.999 --> 99:59:59.999 and they're very good at staying alive. 99:59:59.999 --> 99:59:59.999 And, like most super villains these days, 99:59:59.999 --> 99:59:59.999 their super powers come from a genetic mutation. 99:59:59.999 --> 99:59:59.999 The genes that are modified inside these tumor cells 99:59:59.999 --> 99:59:59.999 can enable and encode for new and unimagined modes of survival, 99:59:59.999 --> 99:59:59.999 allowing the cancer cell to live through 99:59:59.999 --> 99:59:59.999 even our best chemotherapy treatments. 99:59:59.999 --> 99:59:59.999 One example is a trick in which a gene allows 99:59:59.999 --> 99:59:59.999 a cell, even as the drug approaches the cell, 99:59:59.999 --> 99:59:59.999 to push the drug out before the drug can have any effect. 99:59:59.999 --> 99:59:59.999 Imagine the cell effectively spits out the drug. 99:59:59.999 --> 99:59:59.999 This is just one example of the many genetic tricks 99:59:59.999 --> 99:59:59.999 in the bad of our super villain, cancer. 99:59:59.999 --> 99:59:59.999 All due to mutant genes. 99:59:59.999 --> 99:59:59.999 So, we have a super villain with incredible super powers 99:59:59.999 --> 99:59:59.999 and we need a new and powerful mode of attack. 99:59:59.999 --> 99:59:59.999 Actually, we can turn off a gene, 99:59:59.999 --> 99:59:59.999 the key is a set of molecules called siRNA. 99:59:59.999 --> 99:59:59.999 siRNA are short sequences of genetic code 99:59:59.999 --> 99:59:59.999 that guide a cell to block a certain gene. 99:59:59.999 --> 99:59:59.999 Each siRNA molecule can turn off a specific gene 99:59:59.999 --> 99:59:59.999 inside the cell. 99:59:59.999 --> 99:59:59.999 For many years since its discovery, 99:59:59.999 --> 99:59:59.999 scientists have been very excited 99:59:59.999 --> 99:59:59.999 about how we can apply these gene blockers in medicine. 99:59:59.999 --> 99:59:59.999 But, there is a problem. 99:59:59.999 --> 99:59:59.999 siRNA works well inside the cell. 99:59:59.999 --> 99:59:59.999 But if it gets exposed to the enzymes that reside 99:59:59.999 --> 99:59:59.999 in our bloodstream and our tissues, 99:59:59.999 --> 99:59:59.999 it degrades within seconds. 99:59:59.999 --> 99:59:59.999 It has to be packaged, protected through its journey through the body 99:59:59.999 --> 99:59:59.999 on its way to its final target inside the cancer cell. 99:59:59.999 --> 99:59:59.999 So, here's our strategy: 99:59:59.999 --> 99:59:59.999 first, we'll dose the cancer cell with siRNA, the gene blocker, 99:59:59.999 --> 99:59:59.999 and silence those viral genes, 99:59:59.999 --> 99:59:59.999 and they'll we'll whap (?) it with a chemo drug. 99:59:59.999 --> 99:59:59.999 But how do we carry that out? 99:59:59.999 --> 99:59:59.999 Using molecular engineering, 99:59:59.999 --> 99:59:59.999 we can actually design a super weapon 99:59:59.999 --> 99:59:59.999 that can travel through the blood stream. 99:59:59.999 --> 99:59:59.999 It has to be tiny enough that it can get through the blood stream, 99:59:59.999 --> 99:59:59.999 it's got to be small enough to penetrate the tumor tissue, 99:59:59.999 --> 99:59:59.999 and it's got to be tiny enough to be taken up 99:59:59.999 --> 99:59:59.999 inside the cancer cell. 99:59:59.999 --> 99:59:59.999 To do this job well, it has to be about one 100th the size 99:59:59.999 --> 99:59:59.999 of a human hair. 99:59:59.999 --> 99:59:59.999 Let's take a closer look at how we can build this nanoparticle. 99:59:59.999 --> 99:59:59.999 First, let's start with the nanoparticle core. 99:59:59.999 --> 99:59:59.999 It's a tiny capsule that contains the chemotherapy drug. 99:59:59.999 --> 99:59:59.999 This is the poison that will actually end the tumor cell's life. 99:59:59.999 --> 99:59:59.999 Around this core, we'll wrap a very thin, 99:59:59.999 --> 99:59:59.999 nanometer-think blanket of siRNA. 99:59:59.999 --> 99:59:59.999 This is our gene blocker. 99:59:59.999 --> 99:59:59.999 Because siRNA is strongly negatively charged, 99:59:59.999 --> 99:59:59.999 we can protect it with a nice protect layer 99:59:59.999 --> 99:59:59.999 of postively charged polymer. 99:59:59.999 --> 99:59:59.999 The two oppositely charged molecules stick together throough charge attracttion, 99:59:59.999 --> 99:59:59.999 and that provides us with a protective layer 99:59:59.999 --> 99:59:59.999 that prevents the sIRNA from degrading the blood stream. 99:59:59.999 --> 99:59:59.999 We're almost done. 99:59:59.999 --> 99:59:59.999 (Laughter) 99:59:59.999 --> 99:59:59.999 But there is one more big obstacle we have to think about. 99:59:59.999 --> 99:59:59.999 In fact, i tmay be the biggest obstacle of all. 99:59:59.999 --> 99:59:59.999 How do we deploy this super weapon? 99:59:59.999 --> 99:59:59.999 I mean, every good weapon needs to be targeted, 99:59:59.999 --> 99:59:59.999 we need to target this super weapon to the super villain cells 99:59:59.999 --> 99:59:59.999 that we find in the tumor. 99:59:59.999 --> 99:59:59.999 But, our bodies have a natural immune defense system. 99:59:59.999 --> 99:59:59.999 Cells that reside in teh blood stream 99:59:59.999 --> 99:59:59.999 and pick out things that don't belong 99:59:59.999 --> 99:59:59.999 so that it can destroy or elinate them. 99:59:59.999 --> 99:59:59.999 And guess that, our nanoparticle is considered a foreign object. 99:59:59.999 --> 99:59:59.999 We have to sneak our nanoparticle 99:59:59.999 --> 99:59:59.999 past the tumor dfense system, 99:59:59.999 --> 99:59:59.999 we have to get it past this mechanism of getting rid of the foreign object 99:59:59.999 --> 99:59:59.999 bu disguising it. 99:59:59.999 --> 99:59:59.999 So we add one more negatively charged layer 99:59:59.999 --> 99:59:59.999 around this nanoparticle, 99:59:59.999 --> 99:59:59.999 which serves two purposes. 99:59:59.999 --> 99:59:59.999 First, this outer layer is one of the naturally charged, 99:59:59.999 --> 99:59:59.999 highly hydrated polysaccarides that resides in our bodies. 99:59:59.999 --> 99:59:59.999 It creates a cloud of water molecules around the nanoparticle 99:59:59.999 --> 99:59:59.999 that gives us an invisibility cloaking affect. 99:59:59.999 --> 99:59:59.999 This invisibility cloak allows the nanoparticle 99:59:59.999 --> 99:59:59.999 to travel through the bloodstream long and far enough 99:59:59.999 --> 99:59:59.999 to reach the tumor without getting eliminated by the body. 99:59:59.999 --> 99:59:59.999 Second, this layer contains molecules which bind specifically 99:59:59.999 --> 99:59:59.999 to our tumor's cell. 99:59:59.999 --> 99:59:59.999 Once bound, the cancer cell takes up the nanoparticle 99:59:59.999 --> 99:59:59.999 and now we have our nanoparticle inside the cancer cell 99:59:59.999 --> 99:59:59.999 and ready to deploy. 99:59:59.999 --> 99:59:59.999 Alright, I feel the same way, let's go. 99:59:59.999 --> 99:59:59.999 (Applause) 99:59:59.999 --> 99:59:59.999 The siRNA IS DEPLOYED FIRST. 99:59:59.999 --> 99:59:59.999 It acts for hours, 99:59:59.999 --> 99:59:59.999 giving enough time to silence and block those survival genes. 99:59:59.999 --> 99:59:59.999 We have now disabled those genetic superpowers. 99:59:59.999 --> 99:59:59.999 What remains is a cancer cell with no special defenses. 99:59:59.999 --> 99:59:59.999 Then, the chemotherapy drug comes out of the core 99:59:59.999 --> 99:59:59.999 and destroys the tumor cell cleanly and efficiently. 99:59:59.999 --> 99:59:59.999 With sufficient gene blockers, 99:59:59.999 --> 99:59:59.999 we can address many different kinds of mutations. 99:59:59.999 --> 99:59:59.999 Allowing the chance to sweep out tumors, without leaving behind any bad guys. 99:59:59.999 --> 99:59:59.999 So, how does our strategy work? 99:59:59.999 --> 99:59:59.999 We've tested these nano-strucutre particles in animals 99:59:59.999 --> 99:59:59.999 using a highly aggresive form of triple negative breast cancer. 99:59:59.999 --> 99:59:59.999 This triple negative breast cancer exhibits the gene 99:59:59.999 --> 99:59:59.999 that spits out cancer drugs as soon as its delivered. 99:59:59.999 --> 99:59:59.999 Usually, ?, let's call it ? 99:59:59.999 --> 99:59:59.999 is the cancer drug that is the first line of treatment 99:59:59.999 --> 99:59:59.999 for breast cancer. 99:59:59.999 --> 99:59:59.999 So, we first treated our animals with dox core, dox only. 99:59:59.999 --> 99:59:59.999 The tumor slowed their rate of growth, 99:59:59.999 --> 99:59:59.999 but they still grew rapidly, 99:59:59.999 --> 99:59:59.999 doubling in size over a period of two weeks. 99:59:59.999 --> 99:59:59.999 Then, we tried our combination super weapon. 99:59:59.999 --> 99:59:59.999 And now layer a particle with siRNA against the chemo pump, 99:59:59.999 --> 99:59:59.999 plus, we have the doxs in the core. 99:59:59.999 --> 99:59:59.999 And look, we found that not only did the tumors stop growing, 99:59:59.999 --> 99:59:59.999 they actually decerased in size 99:59:59.999 --> 99:59:59.999 and were elimintaed in some cases. 99:59:59.999 --> 99:59:59.999 The tumors were actually regressin. 99:59:59.999 --> 99:59:59.999 (Applause) 99:59:59.999 --> 99:59:59.999 What's great about this approach is that it can be personalized, 99:59:59.999 --> 99:59:59.999 we can add many different layers of siRNA 99:59:59.999 --> 99:59:59.999 to address different mutations and tumor defense mechanisms 99:59:59.999 --> 99:59:59.999 and we can put different drugs into the nanoparticle core. 99:59:59.999 --> 99:59:59.999 As doctors learn how to test patients and understand 99:59:59.999 --> 99:59:59.999 certain tumor genetic types, 99:59:59.999 --> 99:59:59.999 they can help us determine which patients 99:59:59.999 --> 99:59:59.999 can benefit from this strategy 99:59:59.999 --> 99:59:59.999 and which gene blockers we can use. 99:59:59.999 --> 99:59:59.999 Ovarian cancer strikes a special chord with me. 99:59:59.999 --> 99:59:59.999 It is a very aggresive cancer, 99:59:59.999 --> 99:59:59.999 in part because it's discovred at very late stages 99:59:59.999 --> 99:59:59.999 when its highly advanced 99:59:59.999 --> 99:59:59.999 and there are a number of genetic mutations. 99:59:59.999 --> 99:59:59.999 After the first round of chemotherapy, 99:59:59.999 --> 99:59:59.999 this cancer comes back for 75 percent of patients. 99:59:59.999 --> 99:59:59.999 And it usually comes back in a drug resistant form. 99:59:59.999 --> 99:59:59.999 High-grade ovarian cancer is one of 99:59:59.999 --> 99:59:59.999 the biggest super villains out there. 99:59:59.999 --> 99:59:59.999 And we're now directlng this super weapon 99:59:59.999 --> 99:59:59.999 towards its defeat. 99:59:59.999 --> 99:59:59.999 As a researcher, 99:59:59.999 --> 99:59:59.999 I usually don't get to work with patients, 99:59:59.999 --> 99:59:59.999 but I recently met a mother 99:59:59.999 --> 99:59:59.999 who is an ovarian cancer survivor, Mimi and her daughter pAIGE. 99:59:59.999 --> 99:59:59.999 I was deeply inspired 99:59:59.999 --> 99:59:59.999 by the optimism and strength 99:59:59.999 --> 99:59:59.999 that both mother and daughter displayed. 99:59:59.999 --> 99:59:59.999 And by their story of courage and support. 99:59:59.999 --> 99:59:59.999 At this event, we spoke about the different technologies 99:59:59.999 --> 99:59:59.999 directed at cancer. 99:59:59.999 --> 99:59:59.999 And Mimi was in tears as she explained how 99:59:59.999 --> 99:59:59.999 learning about these efforts 99:59:59.999 --> 99:59:59.999 gives her hope for future generations, 99:59:59.999 --> 99:59:59.999 including her own daughter. 99:59:59.999 --> 99:59:59.999 This really touched me. 99:59:59.999 --> 99:59:59.999 It's not just about building really elegant science, 99:59:59.999 --> 99:59:59.999 it's about changing people's lives. 99:59:59.999 --> 99:59:59.999 It's about understanding the power of engineering 99:59:59.999 --> 99:59:59.999 on the scale of molecules. 99:59:59.999 --> 99:59:59.999 I know that as students like Paige 99:59:59.999 --> 99:59:59.999 move forward in their careers, 99:59:59.999 --> 99:59:59.999 they'll open new possibilites 99:59:59.999 --> 99:59:59.999 in addressing some of the big health problems in the world. 99:59:59.999 --> 99:59:59.999 Including, ovarian cancer, neurological disorders, 99:59:59.999 --> 99:59:59.999 and infectious disease. 99:59:59.999 --> 99:59:59.999 Just as chemical engineering has found a way 99:59:59.999 --> 99:59:59.999 to open doors for me. 99:59:59.999 --> 99:59:59.999 Has provided a way of engineering on the tiniest scale 99:59:59.999 --> 99:59:59.999 that of molecules 99:59:59.999 --> 99:59:59.999 to heal on the human scale. 99:59:59.999 --> 99:59:59.999 Thank you 99:59:59.999 --> 99:59:59.999 (Applause)