[Script Info] Title: [Events] Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text Dialogue: 0,0:00:03.22,0:00:06.42,Default,,0000,0000,0000,,I think we can all pretty much agree Dialogue: 0,0:00:06.42,0:00:09.93,Default,,0000,0000,0000,,that germs are really annoying. Dialogue: 0,0:00:11.06,0:00:14.43,Default,,0000,0000,0000,,You can take my word for this\Nbecause I'm kind of an expert. Dialogue: 0,0:00:14.43,0:00:16.79,Default,,0000,0000,0000,,Not only because I work\Nwith viruses for a living, Dialogue: 0,0:00:16.79,0:00:18.20,Default,,0000,0000,0000,,which I do, Dialogue: 0,0:00:18.20,0:00:21.63,Default,,0000,0000,0000,,but mainly because I have\Ntwo young sons at home. Dialogue: 0,0:00:21.63,0:00:22.88,Default,,0000,0000,0000,,They're four and two, Dialogue: 0,0:00:22.88,0:00:25.79,Default,,0000,0000,0000,,and I swear they are germ factories. Dialogue: 0,0:00:25.79,0:00:28.98,Default,,0000,0000,0000,,It seems like every single week\Nthey are sick with something. Dialogue: 0,0:00:28.98,0:00:31.14,Default,,0000,0000,0000,,They have some upper respiratory, Dialogue: 0,0:00:31.14,0:00:33.24,Default,,0000,0000,0000,,lower respiratory, diarrhea, vomiting, Dialogue: 0,0:00:33.24,0:00:35.94,Default,,0000,0000,0000,,you name it, they've been infected. Dialogue: 0,0:00:35.94,0:00:39.79,Default,,0000,0000,0000,,What that means is I am constantly sick. Dialogue: 0,0:00:41.07,0:00:43.95,Default,,0000,0000,0000,,So, yes, germs are a real big pain. Dialogue: 0,0:00:43.95,0:00:46.20,Default,,0000,0000,0000,,But luckily if it's a bacterial infection Dialogue: 0,0:00:46.20,0:00:49.18,Default,,0000,0000,0000,,you can treat it with antibiotics, Dialogue: 0,0:00:49.18,0:00:50.66,Default,,0000,0000,0000,,but if it's a viral infection Dialogue: 0,0:00:50.66,0:00:52.56,Default,,0000,0000,0000,,you just kind of wait it out, right? Dialogue: 0,0:00:52.56,0:00:55.68,Default,,0000,0000,0000,,But luckily most of the infections\Nare not that bad Dialogue: 0,0:00:55.68,0:00:59.12,Default,,0000,0000,0000,,and my kids will cure them\Nin a couple of weeks. Dialogue: 0,0:00:59.12,0:01:01.69,Default,,0000,0000,0000,,But we also know\Nthat there are a lot of other viruses Dialogue: 0,0:01:01.69,0:01:03.69,Default,,0000,0000,0000,,that lead to more significant problems. Dialogue: 0,0:01:03.69,0:01:07.46,Default,,0000,0000,0000,,It can range from maybe\Nhaving life-long cold sores Dialogue: 0,0:01:07.46,0:01:12.33,Default,,0000,0000,0000,,to something more serious\Nlike debilitation or even death. Dialogue: 0,0:01:12.33,0:01:15.17,Default,,0000,0000,0000,,So in general viruses are something Dialogue: 0,0:01:15.17,0:01:17.26,Default,,0000,0000,0000,,I want to stay away from. Dialogue: 0,0:01:17.26,0:01:19.71,Default,,0000,0000,0000,,They're nasty. Dialogue: 0,0:01:20.02,0:01:22.34,Default,,0000,0000,0000,,But now let me introduce you to my mom. Dialogue: 0,0:01:22.34,0:01:25.32,Default,,0000,0000,0000,,This picture was taken in December 2008. Dialogue: 0,0:01:25.32,0:01:26.81,Default,,0000,0000,0000,,We were visiting my brother, Dialogue: 0,0:01:26.81,0:01:28.56,Default,,0000,0000,0000,,who lived in Hawaii at that time. Dialogue: 0,0:01:28.56,0:01:32.56,Default,,0000,0000,0000,,My mom loves golf,\Nher family and warm weather. Dialogue: 0,0:01:33.20,0:01:34.93,Default,,0000,0000,0000,,Probably in that order. Dialogue: 0,0:01:34.93,0:01:38.26,Default,,0000,0000,0000,,So Hawaii is really her paradise. Dialogue: 0,0:01:38.44,0:01:41.70,Default,,0000,0000,0000,,We had a really great time,\Nit was really fun. Dialogue: 0,0:01:42.22,0:01:45.20,Default,,0000,0000,0000,,Unfortunately, when I took this picture, Dialogue: 0,0:01:45.49,0:01:48.26,Default,,0000,0000,0000,,I didn't realize that my mom's body Dialogue: 0,0:01:48.26,0:01:51.16,Default,,0000,0000,0000,,was in the process of betraying her. Dialogue: 0,0:01:51.16,0:01:55.97,Default,,0000,0000,0000,,Because just six months later\Nshe was diagnosed with breast cancer. Dialogue: 0,0:01:56.29,0:01:58.00,Default,,0000,0000,0000,,When she was diagnosed, Dialogue: 0,0:01:58.00,0:01:59.89,Default,,0000,0000,0000,,I was pregnant with my first son. Dialogue: 0,0:01:59.89,0:02:04.21,Default,,0000,0000,0000,,So it became this big\Nemotionally confusing time for me. Dialogue: 0,0:02:04.21,0:02:06.56,Default,,0000,0000,0000,,Because there I was, Dialogue: 0,0:02:06.56,0:02:08.96,Default,,0000,0000,0000,,growing life in my body, Dialogue: 0,0:02:08.96,0:02:10.78,Default,,0000,0000,0000,,and there she was, Dialogue: 0,0:02:10.78,0:02:12.80,Default,,0000,0000,0000,,growing what could potentially Dialogue: 0,0:02:12.80,0:02:14.82,Default,,0000,0000,0000,,be her death. Dialogue: 0,0:02:15.43,0:02:17.87,Default,,0000,0000,0000,,And in addition, since I was pregnant, Dialogue: 0,0:02:17.87,0:02:20.15,Default,,0000,0000,0000,,I was starting to appreciate Dialogue: 0,0:02:20.15,0:02:21.98,Default,,0000,0000,0000,,the female breasts as something Dialogue: 0,0:02:21.98,0:02:23.92,Default,,0000,0000,0000,,that provides sustenance, right? Dialogue: 0,0:02:23.92,0:02:26.42,Default,,0000,0000,0000,,They're supposed to support life. Dialogue: 0,0:02:26.42,0:02:31.54,Default,,0000,0000,0000,,But hers may ultimately\Nbe the source of her demise. Dialogue: 0,0:02:32.27,0:02:35.23,Default,,0000,0000,0000,,So it was a very difficult time. Dialogue: 0,0:02:35.23,0:02:37.80,Default,,0000,0000,0000,,In a couple months after her diagnosis, Dialogue: 0,0:02:37.80,0:02:39.99,Default,,0000,0000,0000,,she started her cancer treatment. Dialogue: 0,0:02:39.99,0:02:43.30,Default,,0000,0000,0000,,Chemo, surgery, radiation. Dialogue: 0,0:02:43.97,0:02:46.37,Default,,0000,0000,0000,,It was a very difficult time. Dialogue: 0,0:02:46.37,0:02:48.38,Default,,0000,0000,0000,,And all the things that you hear Dialogue: 0,0:02:48.38,0:02:52.40,Default,,0000,0000,0000,,about cancer treatment,\Nespecially chemo being horrible, Dialogue: 0,0:02:52.40,0:02:55.21,Default,,0000,0000,0000,,it's true, it is really horrible. Dialogue: 0,0:02:55.21,0:02:57.70,Default,,0000,0000,0000,,And this is something\Nthat you will not appreciate Dialogue: 0,0:02:57.70,0:03:01.61,Default,,0000,0000,0000,,unless you or someone you love\Ngoes through it. Dialogue: 0,0:03:01.81,0:03:03.17,Default,,0000,0000,0000,,But we've made it. Dialogue: 0,0:03:03.17,0:03:05.33,Default,,0000,0000,0000,,We made it through that long, intense year Dialogue: 0,0:03:05.33,0:03:06.91,Default,,0000,0000,0000,,and at her cancer hospital Dialogue: 0,0:03:06.91,0:03:09.23,Default,,0000,0000,0000,,there's this bell\Nthat they hung on the wall Dialogue: 0,0:03:09.23,0:03:12.39,Default,,0000,0000,0000,,and at the end of the year\Nyou can go and ring that bell, Dialogue: 0,0:03:12.39,0:03:15.50,Default,,0000,0000,0000,,telling everyone \Nyou're done with treatment, Dialogue: 0,0:03:15.50,0:03:17.30,Default,,0000,0000,0000,,you're done with cancer. Dialogue: 0,0:03:17.30,0:03:19.50,Default,,0000,0000,0000,,So we were very happy that day, Dialogue: 0,0:03:19.50,0:03:21.40,Default,,0000,0000,0000,,but that happiness and that relief Dialogue: 0,0:03:21.40,0:03:24.81,Default,,0000,0000,0000,,was extremely short-lived. Dialogue: 0,0:03:25.57,0:03:27.82,Default,,0000,0000,0000,,And the worry starts to creep in. Dialogue: 0,0:03:27.82,0:03:29.85,Default,,0000,0000,0000,,The source of that worry Dialogue: 0,0:03:29.85,0:03:31.95,Default,,0000,0000,0000,,is because of this one word. Dialogue: 0,0:03:31.95,0:03:33.87,Default,,0000,0000,0000,,This one word has so much power. Dialogue: 0,0:03:33.87,0:03:35.87,Default,,0000,0000,0000,,Metastasis. Dialogue: 0,0:03:35.87,0:03:37.66,Default,,0000,0000,0000,,Metastasis is where the cancer Dialogue: 0,0:03:37.66,0:03:40.23,Default,,0000,0000,0000,,that originated in one part of the body Dialogue: 0,0:03:40.23,0:03:43.12,Default,,0000,0000,0000,,spreads and moves\Nto different parts of your body, Dialogue: 0,0:03:43.12,0:03:46.42,Default,,0000,0000,0000,,to set up tumors elsewhere. Dialogue: 0,0:03:46.84,0:03:49.92,Default,,0000,0000,0000,,According to the American Cancer Society, Dialogue: 0,0:03:49.92,0:03:53.23,Default,,0000,0000,0000,,if the cancer cells\Nare found just in your breasts, Dialogue: 0,0:03:53.23,0:03:56.54,Default,,0000,0000,0000,,your 5-year relative survival rate\Nis 99 percent. Dialogue: 0,0:03:56.54,0:03:57.97,Default,,0000,0000,0000,,Which is great. Dialogue: 0,0:03:59.51,0:04:01.55,Default,,0000,0000,0000,,But you can see that if cancer cells Dialogue: 0,0:04:01.55,0:04:04.43,Default,,0000,0000,0000,,are found at distant metastatic sites, Dialogue: 0,0:04:04.43,0:04:08.70,Default,,0000,0000,0000,,your survival rate drops to 24 percent. Dialogue: 0,0:04:09.91,0:04:11.77,Default,,0000,0000,0000,,That is scary. Dialogue: 0,0:04:12.95,0:04:15.90,Default,,0000,0000,0000,,Hence, we have one\Nof the greatest challenges Dialogue: 0,0:04:15.90,0:04:18.23,Default,,0000,0000,0000,,to modern medicine. Dialogue: 0,0:04:18.86,0:04:21.81,Default,,0000,0000,0000,,Which is, how do we deliver\Nthese toxic drugs, Dialogue: 0,0:04:21.81,0:04:24.02,Default,,0000,0000,0000,,these messages of death, if you will, Dialogue: 0,0:04:24.02,0:04:26.45,Default,,0000,0000,0000,,just to those metastatic cancer cells? Dialogue: 0,0:04:26.45,0:04:28.42,Default,,0000,0000,0000,,When we're talking about delivery, Dialogue: 0,0:04:28.42,0:04:31.44,Default,,0000,0000,0000,,there are really two factors\Nthat you must consider. Dialogue: 0,0:04:31.44,0:04:33.66,Default,,0000,0000,0000,,One is efficiency. Dialogue: 0,0:04:33.66,0:04:36.58,Default,,0000,0000,0000,,How well can you get these drugs,\Nthese messages of death, Dialogue: 0,0:04:36.58,0:04:38.24,Default,,0000,0000,0000,,just to the cancer cells, right? Dialogue: 0,0:04:38.24,0:04:40.01,Default,,0000,0000,0000,,And the second is specificity. Dialogue: 0,0:04:40.01,0:04:41.72,Default,,0000,0000,0000,,That's where you want those drugs Dialogue: 0,0:04:41.72,0:04:43.88,Default,,0000,0000,0000,,delivered just to the cancer cells, Dialogue: 0,0:04:43.88,0:04:45.51,Default,,0000,0000,0000,,those metastatic cancer cells, Dialogue: 0,0:04:45.51,0:04:48.92,Default,,0000,0000,0000,,but leave all the other\Nhealthy tissues alone. Dialogue: 0,0:04:48.92,0:04:52.52,Default,,0000,0000,0000,,And that will decrease\Nthose horrible side effects. Dialogue: 0,0:04:52.80,0:04:55.25,Default,,0000,0000,0000,,The question is, how? Dialogue: 0,0:04:56.41,0:05:00.24,Default,,0000,0000,0000,,In my work,\Nthe answer lies with the virus. Dialogue: 0,0:05:01.22,0:05:05.34,Default,,0000,0000,0000,,Viruses are nature's nano-cell machines Dialogue: 0,0:05:05.34,0:05:08.01,Default,,0000,0000,0000,,that have evolved to deliver genes, Dialogue: 0,0:05:08.01,0:05:09.68,Default,,0000,0000,0000,,or deliver messages Dialogue: 0,0:05:09.68,0:05:11.100,Default,,0000,0000,0000,,into those cells. Dialogue: 0,0:05:11.100,0:05:14.71,Default,,0000,0000,0000,,They are incredibly good at their job. Dialogue: 0,0:05:14.71,0:05:16.33,Default,,0000,0000,0000,,So what we're trying to do Dialogue: 0,0:05:16.33,0:05:19.52,Default,,0000,0000,0000,,is engineer viruses to treat cancer. Dialogue: 0,0:05:21.96,0:05:23.23,Default,,0000,0000,0000,,Let me introduce you now Dialogue: 0,0:05:23.23,0:05:24.71,Default,,0000,0000,0000,,to the virus that we work on. Dialogue: 0,0:05:24.71,0:05:27.40,Default,,0000,0000,0000,,It's called the adeno-associated virus, Dialogue: 0,0:05:27.40,0:05:28.90,Default,,0000,0000,0000,,it's a very benign virus, Dialogue: 0,0:05:28.90,0:05:31.37,Default,,0000,0000,0000,,it is not linked to any disease. Dialogue: 0,0:05:31.37,0:05:33.97,Default,,0000,0000,0000,,Actually most of us,\N80 to 90 percent of us Dialogue: 0,0:05:33.97,0:05:35.08,Default,,0000,0000,0000,,sitting here today, Dialogue: 0,0:05:35.08,0:05:37.73,Default,,0000,0000,0000,,we've already been infected by this virus. Dialogue: 0,0:05:38.54,0:05:42.93,Default,,0000,0000,0000,,So I'm showing you here\Nthe outside shell of this virus. Dialogue: 0,0:05:42.93,0:05:44.73,Default,,0000,0000,0000,,It is empty on the inside, Dialogue: 0,0:05:44.73,0:05:47.66,Default,,0000,0000,0000,,so that it could carry\Na very small piece of DNA Dialogue: 0,0:05:47.66,0:05:49.85,Default,,0000,0000,0000,,that encodes for that message Dialogue: 0,0:05:49.85,0:05:53.63,Default,,0000,0000,0000,,that you would want to deliver\Nto the cancer cells. Dialogue: 0,0:05:54.15,0:05:58.32,Default,,0000,0000,0000,,And so when I look\Nat images like this, of the virus, Dialogue: 0,0:05:58.92,0:06:02.53,Default,,0000,0000,0000,,I am convinced\Nthat Mother Nature is an artist. Dialogue: 0,0:06:03.33,0:06:07.15,Default,,0000,0000,0000,,Not only that,\Nshe is a proficient designer. Dialogue: 0,0:06:08.06,0:06:11.52,Default,,0000,0000,0000,,The tight interlock\Nbetween form and function Dialogue: 0,0:06:12.30,0:06:15.01,Default,,0000,0000,0000,,is fundamental for design. Dialogue: 0,0:06:15.36,0:06:18.58,Default,,0000,0000,0000,,This virus is only\N25 nanometers in diameter, Dialogue: 0,0:06:19.42,0:06:23.86,Default,,0000,0000,0000,,which is 4,000 times smaller\Nthan the width of your hair. Dialogue: 0,0:06:24.20,0:06:26.74,Default,,0000,0000,0000,,So, in this tiny little package, Dialogue: 0,0:06:27.30,0:06:30.02,Default,,0000,0000,0000,,Nature doesn't really\Nhave a lot of wiggle room Dialogue: 0,0:06:30.02,0:06:32.00,Default,,0000,0000,0000,,to include things that are not important Dialogue: 0,0:06:32.00,0:06:34.05,Default,,0000,0000,0000,,for the ultimate function of the virus. Dialogue: 0,0:06:34.05,0:06:36.57,Default,,0000,0000,0000,,Which is to infect cells. Dialogue: 0,0:06:37.45,0:06:39.70,Default,,0000,0000,0000,,The other thing I want to point out Dialogue: 0,0:06:39.70,0:06:42.79,Default,,0000,0000,0000,,is that viruses are old technology. Dialogue: 0,0:06:44.30,0:06:47.64,Default,,0000,0000,0000,,I mean, it's really,\Nreally old technology. Dialogue: 0,0:06:48.14,0:06:49.91,Default,,0000,0000,0000,,Billions of years. Dialogue: 0,0:06:49.91,0:06:51.74,Default,,0000,0000,0000,,What we're trying to do Dialogue: 0,0:06:51.74,0:06:53.58,Default,,0000,0000,0000,,is to simply piggy-back Dialogue: 0,0:06:53.58,0:06:56.50,Default,,0000,0000,0000,,on Mother Nature's work. Dialogue: 0,0:06:56.76,0:06:59.88,Default,,0000,0000,0000,,To program these viruses to kill cancer. Dialogue: 0,0:07:03.11,0:07:05.68,Default,,0000,0000,0000,,Our over-arching strategy, in our lab, Dialogue: 0,0:07:05.68,0:07:08.05,Default,,0000,0000,0000,,is to program synthetic algorithms Dialogue: 0,0:07:08.05,0:07:09.83,Default,,0000,0000,0000,,into the virus structure, Dialogue: 0,0:07:09.83,0:07:11.55,Default,,0000,0000,0000,,in order to train it to pick out Dialogue: 0,0:07:11.55,0:07:14.67,Default,,0000,0000,0000,,those cancer cells and to destroy them. Dialogue: 0,0:07:15.83,0:07:18.28,Default,,0000,0000,0000,,Now, it turns out, that you can already Dialogue: 0,0:07:18.28,0:07:22.02,Default,,0000,0000,0000,,think of viruses\Nas nanoscopic computers. Dialogue: 0,0:07:22.89,0:07:25.32,Default,,0000,0000,0000,,They have evolved to detect Dialogue: 0,0:07:25.32,0:07:26.92,Default,,0000,0000,0000,,biomolecular signals Dialogue: 0,0:07:26.92,0:07:28.32,Default,,0000,0000,0000,,in their environment, Dialogue: 0,0:07:28.32,0:07:29.93,Default,,0000,0000,0000,,which could include Dialogue: 0,0:07:29.93,0:07:32.04,Default,,0000,0000,0000,,biomolecular cues in our bodies, Dialogue: 0,0:07:32.04,0:07:34.98,Default,,0000,0000,0000,,in order to have productive infections Dialogue: 0,0:07:34.98,0:07:38.56,Default,,0000,0000,0000,,that lead to self-replication ultimately. Dialogue: 0,0:07:40.09,0:07:43.47,Default,,0000,0000,0000,,In every step\Nof the virus infectious process Dialogue: 0,0:07:43.47,0:07:46.51,Default,,0000,0000,0000,,the virus detects biomolecular signals Dialogue: 0,0:07:46.51,0:07:48.72,Default,,0000,0000,0000,,that allow the virus to do the next step Dialogue: 0,0:07:48.72,0:07:50.96,Default,,0000,0000,0000,,of that infection, Dialogue: 0,0:07:50.96,0:07:52.65,Default,,0000,0000,0000,,and t's actually very fascinating, Dialogue: 0,0:07:52.65,0:07:54.60,Default,,0000,0000,0000,,because it turns out that every Dialogue: 0,0:07:54.60,0:07:58.11,Default,,0000,0000,0000,,biomolecular signal acts upon the capsid, Dialogue: 0,0:07:58.11,0:08:01.53,Default,,0000,0000,0000,,changing it, sometimes just a little bit, Dialogue: 0,0:08:01.53,0:08:04.28,Default,,0000,0000,0000,,and sometimes quite dramatically. Dialogue: 0,0:08:05.31,0:08:06.90,Default,,0000,0000,0000,,So you can think of viruses Dialogue: 0,0:08:06.90,0:08:10.19,Default,,0000,0000,0000,,as some of the most primitive\Nshape-shifters. Dialogue: 0,0:08:12.42,0:08:15.11,Default,,0000,0000,0000,,In our work, we're basically taking Dialogue: 0,0:08:15.11,0:08:18.23,Default,,0000,0000,0000,,these intrinsic properties of viruses Dialogue: 0,0:08:18.23,0:08:21.49,Default,,0000,0000,0000,,as inspiration and we want to re-write Dialogue: 0,0:08:21.49,0:08:25.04,Default,,0000,0000,0000,,or re-program what the virus Dialogue: 0,0:08:25.04,0:08:28.90,Default,,0000,0000,0000,,detects and computes\Nas biomolecular input. Dialogue: 0,0:08:31.24,0:08:32.68,Default,,0000,0000,0000,,Here are some of the viruses Dialogue: 0,0:08:32.68,0:08:35.57,Default,,0000,0000,0000,,that we have re-programmed\Nin the laboratory. Dialogue: 0,0:08:35.57,0:08:36.88,Default,,0000,0000,0000,,Just by looking at them, Dialogue: 0,0:08:36.88,0:08:39.33,Default,,0000,0000,0000,,you actually won't be able\Nto tell the difference Dialogue: 0,0:08:39.33,0:08:40.76,Default,,0000,0000,0000,,between our engineered viruses Dialogue: 0,0:08:40.76,0:08:43.57,Default,,0000,0000,0000,,and the ones that exist in Nature. Dialogue: 0,0:08:43.57,0:08:45.35,Default,,0000,0000,0000,,But these are different. Dialogue: 0,0:08:45.35,0:08:47.55,Default,,0000,0000,0000,,These have algorithms Dialogue: 0,0:08:47.55,0:08:50.28,Default,,0000,0000,0000,,programmed into their structure Dialogue: 0,0:08:50.28,0:08:53.55,Default,,0000,0000,0000,,that turns them into\Ncancer-seeking assassins. Dialogue: 0,0:08:53.55,0:08:55.74,Default,,0000,0000,0000,,Let me explain. Dialogue: 0,0:08:56.48,0:08:57.57,Default,,0000,0000,0000,,The basic idea Dialogue: 0,0:08:57.57,0:09:00.05,Default,,0000,0000,0000,,is that we want to create viruses\Nthat will be able Dialogue: 0,0:09:00.05,0:09:01.61,Default,,0000,0000,0000,,to travel throughout the body Dialogue: 0,0:09:01.61,0:09:03.70,Default,,0000,0000,0000,,in an inert fashion, Dialogue: 0,0:09:03.70,0:09:06.64,Default,,0000,0000,0000,,or in a locked configuration, if you will. Dialogue: 0,0:09:06.64,0:09:08.29,Default,,0000,0000,0000,,In this locked configuration Dialogue: 0,0:09:08.29,0:09:10.53,Default,,0000,0000,0000,,the virus cannot deliver the message Dialogue: 0,0:09:10.53,0:09:12.53,Default,,0000,0000,0000,,that it's carrying Dialogue: 0,0:09:12.53,0:09:16.26,Default,,0000,0000,0000,,until it comes across\Nsome biomolecular cue, Dialogue: 0,0:09:16.26,0:09:19.94,Default,,0000,0000,0000,,signal, represented by the key here, Dialogue: 0,0:09:19.94,0:09:22.08,Default,,0000,0000,0000,,and that key will open up the capsid Dialogue: 0,0:09:22.08,0:09:25.11,Default,,0000,0000,0000,,and now, in this open configuration, Dialogue: 0,0:09:25.11,0:09:27.55,Default,,0000,0000,0000,,the virus can deliver that message Dialogue: 0,0:09:27.55,0:09:30.11,Default,,0000,0000,0000,,to the cancer cells. Dialogue: 0,0:09:30.30,0:09:32.38,Default,,0000,0000,0000,,The other way that I like to conceptualize Dialogue: 0,0:09:32.38,0:09:34.27,Default,,0000,0000,0000,,our design strategy is thinking of it Dialogue: 0,0:09:34.27,0:09:36.64,Default,,0000,0000,0000,,as if we were programming encryption Dialogue: 0,0:09:36.64,0:09:38.72,Default,,0000,0000,0000,,into these viruses. Dialogue: 0,0:09:39.02,0:09:41.44,Default,,0000,0000,0000,,So, the message cannot be read Dialogue: 0,0:09:41.44,0:09:45.44,Default,,0000,0000,0000,,unless it is deciphered\Nby the appropriate key. Dialogue: 0,0:09:47.59,0:09:51.28,Default,,0000,0000,0000,,The next natural question is, what key? Dialogue: 0,0:09:52.30,0:09:55.04,Default,,0000,0000,0000,,Luckily, advances in biomedical research Dialogue: 0,0:09:55.04,0:09:58.01,Default,,0000,0000,0000,,has been answering that question for us. Dialogue: 0,0:09:58.01,0:10:00.17,Default,,0000,0000,0000,,It turns out that if you look\Nat tumor cells, Dialogue: 0,0:10:00.17,0:10:02.60,Default,,0000,0000,0000,,tumor masses, there are a lot Dialogue: 0,0:10:02.60,0:10:05.66,Default,,0000,0000,0000,,of biochemical signals, these cues, Dialogue: 0,0:10:05.66,0:10:07.99,Default,,0000,0000,0000,,that are present at higher concentrations Dialogue: 0,0:10:07.99,0:10:12.44,Default,,0000,0000,0000,,in the tumor,\Neither outside of the cancer cells Dialogue: 0,0:10:12.44,0:10:15.25,Default,,0000,0000,0000,,or within the cancer cells themselves. Dialogue: 0,0:10:15.25,0:10:17.85,Default,,0000,0000,0000,,You can imagine all of these cues Dialogue: 0,0:10:17.85,0:10:19.70,Default,,0000,0000,0000,,can act as the key Dialogue: 0,0:10:19.70,0:10:22.45,Default,,0000,0000,0000,,that will open up our virus. Dialogue: 0,0:10:23.54,0:10:25.59,Default,,0000,0000,0000,,This is a demonstration of how Dialogue: 0,0:10:25.59,0:10:27.42,Default,,0000,0000,0000,,one of our devices work. Dialogue: 0,0:10:27.42,0:10:29.50,Default,,0000,0000,0000,,In this black part, you don't see anything Dialogue: 0,0:10:29.50,0:10:32.71,Default,,0000,0000,0000,,but there's an entire lawn of cells Dialogue: 0,0:10:33.16,0:10:35.49,Default,,0000,0000,0000,,and onto this lawn we've added\Nthese viruses Dialogue: 0,0:10:35.49,0:10:37.48,Default,,0000,0000,0000,,that we have in here, and in this case Dialogue: 0,0:10:37.48,0:10:40.75,Default,,0000,0000,0000,,the virus is still in its locked state, Dialogue: 0,0:10:40.75,0:10:42.85,Default,,0000,0000,0000,,its encrypted state, Dialogue: 0,0:10:42.85,0:10:46.22,Default,,0000,0000,0000,,and as a demonstration\Nthis virus is delivering a message Dialogue: 0,0:10:46.22,0:10:49.07,Default,,0000,0000,0000,,that, if read properly by that cell, Dialogue: 0,0:10:49.07,0:10:50.92,Default,,0000,0000,0000,,would turn that cell green. Dialogue: 0,0:10:50.92,0:10:53.53,Default,,0000,0000,0000,,It's a green message. Dialogue: 0,0:10:53.53,0:10:56.28,Default,,0000,0000,0000,,You can see there's really not many cells Dialogue: 0,0:10:56.28,0:10:59.04,Default,,0000,0000,0000,,that are able to read that green message. Dialogue: 0,0:10:59.04,0:11:02.60,Default,,0000,0000,0000,,That's mainly because\Nthe virus is encrypted. Dialogue: 0,0:11:04.04,0:11:07.08,Default,,0000,0000,0000,,Conversely, when the virus sees Dialogue: 0,0:11:07.79,0:11:10.66,Default,,0000,0000,0000,,these biomolecular keys, Dialogue: 0,0:11:11.26,0:11:13.30,Default,,0000,0000,0000,,the viruses open, Dialogue: 0,0:11:13.30,0:11:14.94,Default,,0000,0000,0000,,that message is decyphered Dialogue: 0,0:11:14.94,0:11:17.21,Default,,0000,0000,0000,,and these cells can now read Dialogue: 0,0:11:17.21,0:11:20.15,Default,,0000,0000,0000,,these green messages. Dialogue: 0,0:11:21.77,0:11:24.52,Default,,0000,0000,0000,,Let's go back to the schematic here. Dialogue: 0,0:11:24.52,0:11:27.69,Default,,0000,0000,0000,,I told you that there's a lot of keys Dialogue: 0,0:11:28.06,0:11:30.27,Default,,0000,0000,0000,,within the tumor mass, Dialogue: 0,0:11:30.27,0:11:32.44,Default,,0000,0000,0000,,greater concentration in the tumor, Dialogue: 0,0:11:32.44,0:11:35.48,Default,,0000,0000,0000,,but you may have noticed\Nthat there are also keys, Dialogue: 0,0:11:35.49,0:11:38.23,Default,,0000,0000,0000,,present at lower concentrations, Dialogue: 0,0:11:38.23,0:11:40.28,Default,,0000,0000,0000,,elsewhere in the body. Dialogue: 0,0:11:40.28,0:11:42.51,Default,,0000,0000,0000,,And that represents some problem. Dialogue: 0,0:11:42.51,0:11:46.53,Default,,0000,0000,0000,,That could lead to these\Nnon-targeted side effects, Dialogue: 0,0:11:46.53,0:11:49.02,Default,,0000,0000,0000,,that you want to run away from. Dialogue: 0,0:11:49.02,0:11:51.22,Default,,0000,0000,0000,,Our answer to this is trying Dialogue: 0,0:11:51.22,0:11:54.97,Default,,0000,0000,0000,,to make these viruses open Dialogue: 0,0:11:54.97,0:11:57.90,Default,,0000,0000,0000,,only when it detects two, Dialogue: 0,0:11:57.90,0:12:00.51,Default,,0000,0000,0000,,both the red and the green. Dialogue: 0,0:12:00.51,0:12:02.24,Default,,0000,0000,0000,,As shown here. Dialogue: 0,0:12:02.24,0:12:04.16,Default,,0000,0000,0000,,And we have successfully generated Dialogue: 0,0:12:04.16,0:12:07.04,Default,,0000,0000,0000,,one of these devices recently. Dialogue: 0,0:12:07.04,0:12:09.11,Default,,0000,0000,0000,,Another way to think about this Dialogue: 0,0:12:09.11,0:12:12.96,Default,,0000,0000,0000,,is to program an "AND" logic operator Dialogue: 0,0:12:12.96,0:12:15.24,Default,,0000,0000,0000,,into this virus structure. Dialogue: 0,0:12:15.24,0:12:18.99,Default,,0000,0000,0000,,I believe that the virus\Nbiotechnology community Dialogue: 0,0:12:18.99,0:12:20.79,Default,,0000,0000,0000,,we are dreaming the same dream, Dialogue: 0,0:12:20.79,0:12:22.97,Default,,0000,0000,0000,,we have the same vision. Dialogue: 0,0:12:22.97,0:12:24.28,Default,,0000,0000,0000,,In the very near future, Dialogue: 0,0:12:24.28,0:12:26.90,Default,,0000,0000,0000,,we want to be able to program viruses, Dialogue: 0,0:12:26.90,0:12:30.17,Default,,0000,0000,0000,,real viruses, as we would\Ncomputer programs. Dialogue: 0,0:12:30.17,0:12:32.03,Default,,0000,0000,0000,,And we want this design process Dialogue: 0,0:12:32.03,0:12:35.34,Default,,0000,0000,0000,,to be standardized, modular Dialogue: 0,0:12:35.34,0:12:38.49,Default,,0000,0000,0000,,and lead to a predictable outcome. Dialogue: 0,0:12:40.76,0:12:43.63,Default,,0000,0000,0000,,I leave you with a cliff-hanger. Dialogue: 0,0:12:44.03,0:12:45.73,Default,,0000,0000,0000,,The big looming question is, Dialogue: 0,0:12:45.73,0:12:49.10,Default,,0000,0000,0000,,how will these devices work\Nin the human body? Dialogue: 0,0:12:50.51,0:12:54.02,Default,,0000,0000,0000,,Will they actually do\Nwhat we are proposing? Dialogue: 0,0:12:54.69,0:12:57.88,Default,,0000,0000,0000,,We don't know the answers\Nto these questions yet. Dialogue: 0,0:13:01.27,0:13:04.10,Default,,0000,0000,0000,,But I work with a really great team, Dialogue: 0,0:13:04.69,0:13:07.65,Default,,0000,0000,0000,,of very hard-working\Nand passionate students Dialogue: 0,0:13:07.65,0:13:09.61,Default,,0000,0000,0000,,on this research. Dialogue: 0,0:13:09.61,0:13:11.66,Default,,0000,0000,0000,,So follow us and see our progress Dialogue: 0,0:13:11.66,0:13:14.00,Default,,0000,0000,0000,,over the next several years. Dialogue: 0,0:13:14.00,0:13:17.14,Default,,0000,0000,0000,,I invite you. Go viral with us. Dialogue: 0,0:13:17.85,0:13:19.13,Default,,0000,0000,0000,,Thank you. Dialogue: 0,0:13:19.13,0:13:21.38,Default,,0000,0000,0000,,(Applause)