1 99:59:59,999 --> 99:59:59,999 Cancer affects all of us, 2 99:59:59,999 --> 99:59:59,999 especially the ones that come back over and over again. 3 99:59:59,999 --> 99:59:59,999 The highly invasive and drug-resistant ones, 4 99:59:59,999 --> 99:59:59,999 the ones that defy medical treatment, 5 99:59:59,999 --> 99:59:59,999 even when we throw our best drugs at them. 6 99:59:59,999 --> 99:59:59,999 Engineering at the molecular level, 7 99:59:59,999 --> 99:59:59,999 working at the smallest of scales, 8 99:59:59,999 --> 99:59:59,999 can provide exciting new ways 9 99:59:59,999 --> 99:59:59,999 to find the most aggressive forms of cancer. 10 99:59:59,999 --> 99:59:59,999 Cancer is a very clever disease. 11 99:59:59,999 --> 99:59:59,999 There are some forms of cancer, 12 99:59:59,999 --> 99:59:59,999 which, fortunately, we've learned how to address relatively well 13 99:59:59,999 --> 99:59:59,999 with known and established drugs and surgery. 14 99:59:59,999 --> 99:59:59,999 But, there's some forms of cancer that don't respond 15 99:59:59,999 --> 99:59:59,999 to these approaches 16 99:59:59,999 --> 99:59:59,999 and the tumor survives or comes back, 17 99:59:59,999 --> 99:59:59,999 even after an onslaught of drugs. 18 99:59:59,999 --> 99:59:59,999 We can think of these very aggresive forms of cancer 19 99:59:59,999 --> 99:59:59,999 as kind of super villains in a comic book. 20 99:59:59,999 --> 99:59:59,999 They're clever, they're adaptable, 21 99:59:59,999 --> 99:59:59,999 and they're very good at staying alive. 22 99:59:59,999 --> 99:59:59,999 And, like most super villains these days, 23 99:59:59,999 --> 99:59:59,999 their super powers come from a genetic mutation. 24 99:59:59,999 --> 99:59:59,999 The genes that are modified inside these tumor cells 25 99:59:59,999 --> 99:59:59,999 can enable and encode for new and unimagined modes of survival, 26 99:59:59,999 --> 99:59:59,999 allowing the cancer cell to live through 27 99:59:59,999 --> 99:59:59,999 even our best chemotherapy treatments. 28 99:59:59,999 --> 99:59:59,999 One example is a trick in which a gene allows 29 99:59:59,999 --> 99:59:59,999 a cell, even as the drug approaches the cell, 30 99:59:59,999 --> 99:59:59,999 to push the drug out before the drug can have any effect. 31 99:59:59,999 --> 99:59:59,999 Imagine the cell effectively spits out the drug. 32 99:59:59,999 --> 99:59:59,999 This is just one example of the many genetic tricks 33 99:59:59,999 --> 99:59:59,999 in the bad of our super villain, cancer. 34 99:59:59,999 --> 99:59:59,999 All due to mutant genes. 35 99:59:59,999 --> 99:59:59,999 So, we have a super villain with incredible super powers 36 99:59:59,999 --> 99:59:59,999 and we need a new and powerful mode of attack. 37 99:59:59,999 --> 99:59:59,999 Actually, we can turn off a gene, 38 99:59:59,999 --> 99:59:59,999 the key is a set of molecules called siRNA. 39 99:59:59,999 --> 99:59:59,999 siRNA are short sequences of genetic code 40 99:59:59,999 --> 99:59:59,999 that guide a cell to block a certain gene. 41 99:59:59,999 --> 99:59:59,999 Each siRNA molecule can turn off a specific gene 42 99:59:59,999 --> 99:59:59,999 inside the cell. 43 99:59:59,999 --> 99:59:59,999 For many years since its discovery, 44 99:59:59,999 --> 99:59:59,999 scientists have been very excited 45 99:59:59,999 --> 99:59:59,999 about how we can apply these gene blockers in medicine. 46 99:59:59,999 --> 99:59:59,999 But, there is a problem. 47 99:59:59,999 --> 99:59:59,999 siRNA works well inside the cell. 48 99:59:59,999 --> 99:59:59,999 But if it gets exposed to the enzymes that reside 49 99:59:59,999 --> 99:59:59,999 in our bloodstream and our tissues, 50 99:59:59,999 --> 99:59:59,999 it degrades within seconds. 51 99:59:59,999 --> 99:59:59,999 It has to be packaged, protected through its journey through the body 52 99:59:59,999 --> 99:59:59,999 on its way to its final target inside the cancer cell. 53 99:59:59,999 --> 99:59:59,999 So, here's our strategy: 54 99:59:59,999 --> 99:59:59,999 first, we'll dose the cancer cell with siRNA, the gene blocker, 55 99:59:59,999 --> 99:59:59,999 and silence those viral genes, 56 99:59:59,999 --> 99:59:59,999 and they'll we'll whap (?) it with a chemo drug. 57 99:59:59,999 --> 99:59:59,999 But how do we carry that out? 58 99:59:59,999 --> 99:59:59,999 Using molecular engineering, 59 99:59:59,999 --> 99:59:59,999 we can actually design a super weapon 60 99:59:59,999 --> 99:59:59,999 that can travel through the blood stream. 61 99:59:59,999 --> 99:59:59,999 It has to be tiny enough that it can get through the blood stream, 62 99:59:59,999 --> 99:59:59,999 it's got to be small enough to penetrate the tumor tissue, 63 99:59:59,999 --> 99:59:59,999 and it's got to be tiny enough to be taken up 64 99:59:59,999 --> 99:59:59,999 inside the cancer cell. 65 99:59:59,999 --> 99:59:59,999 To do this job well, it has to be about one 100th the size 66 99:59:59,999 --> 99:59:59,999 of a human hair. 67 99:59:59,999 --> 99:59:59,999 Let's take a closer look at how we can build this nanoparticle. 68 99:59:59,999 --> 99:59:59,999 First, let's start with the nanoparticle core. 69 99:59:59,999 --> 99:59:59,999 It's a tiny capsule that contains the chemotherapy drug. 70 99:59:59,999 --> 99:59:59,999 This is the poison that will actually end the tumor cell's life. 71 99:59:59,999 --> 99:59:59,999 Around this core, we'll wrap a very thin, 72 99:59:59,999 --> 99:59:59,999 nanometer-think blanket of siRNA. 73 99:59:59,999 --> 99:59:59,999 This is our gene blocker. 74 99:59:59,999 --> 99:59:59,999 Because siRNA is strongly negatively charged, 75 99:59:59,999 --> 99:59:59,999 we can protect it with a nice protect layer 76 99:59:59,999 --> 99:59:59,999 of postively charged polymer. 77 99:59:59,999 --> 99:59:59,999 The two oppositely charged molecules stick together throough charge attracttion, 78 99:59:59,999 --> 99:59:59,999 and that provides us with a protective layer 79 99:59:59,999 --> 99:59:59,999 that prevents the sIRNA from degrading the blood stream. 80 99:59:59,999 --> 99:59:59,999 We're almost done. 81 99:59:59,999 --> 99:59:59,999 (Laughter) 82 99:59:59,999 --> 99:59:59,999 But there is one more big obstacle we have to think about. 83 99:59:59,999 --> 99:59:59,999 In fact, i tmay be the biggest obstacle of all. 84 99:59:59,999 --> 99:59:59,999 How do we deploy this super weapon? 85 99:59:59,999 --> 99:59:59,999 I mean, every good weapon needs to be targeted, 86 99:59:59,999 --> 99:59:59,999 we need to target this super weapon to the super villain cells 87 99:59:59,999 --> 99:59:59,999 that we find in the tumor. 88 99:59:59,999 --> 99:59:59,999 But, our bodies have a natural immune defense system. 89 99:59:59,999 --> 99:59:59,999 Cells that reside in teh blood stream 90 99:59:59,999 --> 99:59:59,999 and pick out things that don't belong 91 99:59:59,999 --> 99:59:59,999 so that it can destroy or elinate them. 92 99:59:59,999 --> 99:59:59,999 And guess that, our nanoparticle is considered a foreign object. 93 99:59:59,999 --> 99:59:59,999 We have to sneak our nanoparticle 94 99:59:59,999 --> 99:59:59,999 past the tumor dfense system, 95 99:59:59,999 --> 99:59:59,999 we have to get it past this mechanism of getting rid of the foreign object 96 99:59:59,999 --> 99:59:59,999 bu disguising it. 97 99:59:59,999 --> 99:59:59,999 So we add one more negatively charged layer 98 99:59:59,999 --> 99:59:59,999 around this nanoparticle, 99 99:59:59,999 --> 99:59:59,999 which serves two purposes. 100 99:59:59,999 --> 99:59:59,999 First, this outer layer is one of the naturally charged, 101 99:59:59,999 --> 99:59:59,999 highly hydrated polysaccarides that resides in our bodies. 102 99:59:59,999 --> 99:59:59,999 It creates a cloud of water molecules around the nanoparticle 103 99:59:59,999 --> 99:59:59,999 that gives us an invisibility cloaking affect. 104 99:59:59,999 --> 99:59:59,999 This invisibility cloak allows the nanoparticle 105 99:59:59,999 --> 99:59:59,999 to travel through the bloodstream long and far enough 106 99:59:59,999 --> 99:59:59,999 to reach the tumor without getting eliminated by the body. 107 99:59:59,999 --> 99:59:59,999 Second, this layer contains molecules which bind specifically 108 99:59:59,999 --> 99:59:59,999 to our tumor's cell. 109 99:59:59,999 --> 99:59:59,999 Once bound, the cancer cell takes up the nanoparticle 110 99:59:59,999 --> 99:59:59,999 and now we have our nanoparticle inside the cancer cell 111 99:59:59,999 --> 99:59:59,999 and ready to deploy. 112 99:59:59,999 --> 99:59:59,999 Alright, I feel the same way, let's go. 113 99:59:59,999 --> 99:59:59,999 (Applause) 114 99:59:59,999 --> 99:59:59,999 The siRNA IS DEPLOYED FIRST. 115 99:59:59,999 --> 99:59:59,999 It acts for hours, 116 99:59:59,999 --> 99:59:59,999 giving enough time to silence and block those survival genes. 117 99:59:59,999 --> 99:59:59,999 We have now disabled those genetic superpowers. 118 99:59:59,999 --> 99:59:59,999 What remains is a cancer cell with no special defenses. 119 99:59:59,999 --> 99:59:59,999 Then, the chemotherapy drug comes out of the core 120 99:59:59,999 --> 99:59:59,999 and destroys the tumor cell cleanly and efficiently. 121 99:59:59,999 --> 99:59:59,999 With sufficient gene blockers, 122 99:59:59,999 --> 99:59:59,999 we can address many different kinds of mutations. 123 99:59:59,999 --> 99:59:59,999 Allowing the chance to sweep out tumors, without leaving behind any bad guys. 124 99:59:59,999 --> 99:59:59,999 So, how does our strategy work? 125 99:59:59,999 --> 99:59:59,999 We've tested these nano-strucutre particles in animals 126 99:59:59,999 --> 99:59:59,999 using a highly aggresive form of triple negative breast cancer. 127 99:59:59,999 --> 99:59:59,999 This triple negative breast cancer exhibits the gene 128 99:59:59,999 --> 99:59:59,999 that spits out cancer drugs as soon as its delivered. 129 99:59:59,999 --> 99:59:59,999 Usually, ?, let's call it ? 130 99:59:59,999 --> 99:59:59,999 is the cancer drug that is the first line of treatment 131 99:59:59,999 --> 99:59:59,999 for breast cancer. 132 99:59:59,999 --> 99:59:59,999 So, we first treated our animals with dox core, dox only. 133 99:59:59,999 --> 99:59:59,999 The tumor slowed their rate of growth, 134 99:59:59,999 --> 99:59:59,999 but they still grew rapidly, 135 99:59:59,999 --> 99:59:59,999 doubling in size over a period of two weeks. 136 99:59:59,999 --> 99:59:59,999 Then, we tried our combination super weapon. 137 99:59:59,999 --> 99:59:59,999 And now layer a particle with siRNA against the chemo pump, 138 99:59:59,999 --> 99:59:59,999 plus, we have the doxs in the core. 139 99:59:59,999 --> 99:59:59,999 And look, we found that not only did the tumors stop growing, 140 99:59:59,999 --> 99:59:59,999 they actually decerased in size 141 99:59:59,999 --> 99:59:59,999 and were elimintaed in some cases. 142 99:59:59,999 --> 99:59:59,999 The tumors were actually regressin. 143 99:59:59,999 --> 99:59:59,999 (Applause) 144 99:59:59,999 --> 99:59:59,999 What's great about this approach is that it can be personalized, 145 99:59:59,999 --> 99:59:59,999 we can add many different layers of siRNA 146 99:59:59,999 --> 99:59:59,999 to address different mutations and tumor defense mechanisms 147 99:59:59,999 --> 99:59:59,999 and we can put different drugs into the nanoparticle core. 148 99:59:59,999 --> 99:59:59,999 As doctors learn how to test patients and understand 149 99:59:59,999 --> 99:59:59,999 certain tumor genetic types, 150 99:59:59,999 --> 99:59:59,999 they can help us determine which patients 151 99:59:59,999 --> 99:59:59,999 can benefit from this strategy 152 99:59:59,999 --> 99:59:59,999 and which gene blockers we can use. 153 99:59:59,999 --> 99:59:59,999 Ovarian cancer strikes a special chord with me. 154 99:59:59,999 --> 99:59:59,999 It is a very aggresive cancer, 155 99:59:59,999 --> 99:59:59,999 in part because it's discovred at very late stages 156 99:59:59,999 --> 99:59:59,999 when its highly advanced 157 99:59:59,999 --> 99:59:59,999 and there are a number of genetic mutations. 158 99:59:59,999 --> 99:59:59,999 After the first round of chemotherapy, 159 99:59:59,999 --> 99:59:59,999 this cancer comes back for 75 percent of patients. 160 99:59:59,999 --> 99:59:59,999 And it usually comes back in a drug resistant form. 161 99:59:59,999 --> 99:59:59,999 High-grade ovarian cancer is one of 162 99:59:59,999 --> 99:59:59,999 the biggest super villains out there. 163 99:59:59,999 --> 99:59:59,999 And we're now directlng this super weapon 164 99:59:59,999 --> 99:59:59,999 towards its defeat. 165 99:59:59,999 --> 99:59:59,999 As a researcher, 166 99:59:59,999 --> 99:59:59,999 I usually don't get to work with patients, 167 99:59:59,999 --> 99:59:59,999 but I recently met a mother 168 99:59:59,999 --> 99:59:59,999 who is an ovarian cancer survivor, Mimi and her daughter pAIGE. 169 99:59:59,999 --> 99:59:59,999 I was deeply inspired 170 99:59:59,999 --> 99:59:59,999 by the optimism and strength 171 99:59:59,999 --> 99:59:59,999 that both mother and daughter displayed. 172 99:59:59,999 --> 99:59:59,999 And by their story of courage and support. 173 99:59:59,999 --> 99:59:59,999 At this event, we spoke about the different technologies 174 99:59:59,999 --> 99:59:59,999 directed at cancer. 175 99:59:59,999 --> 99:59:59,999 And Mimi was in tears as she explained how 176 99:59:59,999 --> 99:59:59,999 learning about these efforts 177 99:59:59,999 --> 99:59:59,999 gives her hope for future generations, 178 99:59:59,999 --> 99:59:59,999 including her own daughter. 179 99:59:59,999 --> 99:59:59,999 This really touched me. 180 99:59:59,999 --> 99:59:59,999 It's not just about building really elegant science, 181 99:59:59,999 --> 99:59:59,999 it's about changing people's lives. 182 99:59:59,999 --> 99:59:59,999 It's about understanding the power of engineering 183 99:59:59,999 --> 99:59:59,999 on the scale of molecules. 184 99:59:59,999 --> 99:59:59,999 I know that as students like Paige 185 99:59:59,999 --> 99:59:59,999 move forward in their careers, 186 99:59:59,999 --> 99:59:59,999 they'll open new possibilites 187 99:59:59,999 --> 99:59:59,999 in addressing some of the big health problems in the world. 188 99:59:59,999 --> 99:59:59,999 Including, ovarian cancer, neurological disorders, 189 99:59:59,999 --> 99:59:59,999 and infectious disease. 190 99:59:59,999 --> 99:59:59,999 Just as chemical engineering has found a way 191 99:59:59,999 --> 99:59:59,999 to open doors for me. 192 99:59:59,999 --> 99:59:59,999 Has provided a way of engineering on the tiniest scale 193 99:59:59,999 --> 99:59:59,999 that of molecules 194 99:59:59,999 --> 99:59:59,999 to heal on the human scale. 195 99:59:59,999 --> 99:59:59,999 Thank you 196 99:59:59,999 --> 99:59:59,999 (Applause)