0:00:00.917,0:00:03.825 So how are we going to beat[br]this novel coronavirus? 0:00:04.317,0:00:06.948 By using our best tools: 0:00:06.972,0:00:09.011 our science and our technology. 0:00:09.594,0:00:12.726 In my lab, we're using[br]the tools of artificial intelligence 0:00:12.750,0:00:14.329 and synthetic biology 0:00:14.353,0:00:17.413 to speed up the fight[br]against this pandemic. 0:00:18.078,0:00:19.941 Our work was originally designed 0:00:19.965,0:00:22.818 to tackle the antibiotic[br]resistance crisis. 0:00:22.842,0:00:27.531 Our project seeks to harness[br]the power of machine learning 0:00:27.555,0:00:29.401 to replenish our antibiotic arsenal 0:00:29.425,0:00:33.263 and avoid a globally devastating[br]postantibiotic era. 0:00:33.685,0:00:36.505 Importantly, the same[br]technology can be used 0:00:36.529,0:00:38.601 to search for antiviral compounds 0:00:38.625,0:00:41.303 that could help us fight[br]the current pandemic. 0:00:42.080,0:00:45.982 Machine learning is turning[br]the traditional model of drug discovery 0:00:46.006,0:00:47.410 on its head. 0:00:47.434,0:00:48.659 With this approach, 0:00:48.683,0:00:52.761 instead of painstakingly testing[br]thousands of existing molecules 0:00:52.785,0:00:54.221 one by one in a lab 0:00:54.245,0:00:55.832 for their effectiveness, 0:00:55.856,0:01:00.513 we can train a computer[br]to explore the exponentially larger space 0:01:00.537,0:01:04.121 of essentially all possible molecules[br]that could be synthesized, 0:01:04.145,0:01:09.759 and thus, instead of looking[br]for a needle in a haystack, 0:01:09.783,0:01:13.543 we can use the giant magnet[br]of computing power 0:01:13.567,0:01:17.482 to find many needles[br]in multiple haystacks simultaneously. 0:01:18.423,0:01:20.415 We've already had some early success. 0:01:21.010,0:01:26.475 Recently, we used machine learning[br]to discover new antibiotics 0:01:26.499,0:01:29.059 that can help us fight off[br]the bacterial infections 0:01:29.083,0:01:32.694 that can occur alongside[br]SARS-CoV-2 infections. 0:01:33.181,0:01:37.350 Two months ago, TED's Audacious Project[br]approved funding for us 0:01:37.374,0:01:39.562 to massively scale up our work 0:01:39.586,0:01:44.214 with the goal of discovering[br]seven new classes of antibiotics 0:01:44.238,0:01:47.721 against seven of the world's[br]deadly bacterial pathogens 0:01:47.745,0:01:49.800 over the next seven years. 0:01:50.206,0:01:51.939 For context: 0:01:51.963,0:01:53.891 the number of new class of antibiotics 0:01:53.915,0:01:57.150 that have been discovered[br]over the last three decades is zero. 0:01:58.030,0:02:01.601 While the quest for new antibiotics[br]is for our medium-term future, 0:02:01.625,0:02:06.277 the novel coronavirus poses[br]an immediate deadly threat, 0:02:06.301,0:02:10.094 and I'm excited to share that we think[br]we can use the same technology 0:02:10.118,0:02:12.927 to search for therapeutics[br]to fight this virus. 0:02:13.486,0:02:15.205 So how are we going to do it? 0:02:15.229,0:02:18.177 Well, we're creating[br]a compound training library 0:02:18.201,0:02:23.743 and with collaborators applying these[br]molecules to SARS-CoV-2-infected cells 0:02:23.767,0:02:27.661 to see which of them exhibit[br]effective activity. 0:02:28.175,0:02:31.367 These data will be use to train[br]a machine learning model 0:02:31.391,0:02:35.461 that will be applied to an in silico[br]library of over a billion molecules 0:02:35.485,0:02:39.689 to search for potential[br]novel antiviral compounds. 0:02:40.324,0:02:42.982 We will synthesize and test[br]the top predictions 0:02:43.006,0:02:45.895 and advance the most promising[br]candidates into the clinic. 0:02:46.356,0:02:48.134 Sound too good to be true? 0:02:48.158,0:02:49.590 Well, it shouldn't. 0:02:49.614,0:02:52.939 The Antibiotics AI Project is founded[br]on our proof of concept research 0:02:52.963,0:02:56.364 that led to the discovery[br]of a novel broad-spectrum antibiotic 0:02:56.388,0:02:57.573 called halicin. 0:02:58.443,0:03:01.256 Halicin has potent antibacterial activity 0:03:01.280,0:03:05.382 against almost all antibiotic-resistant[br]bacterial pathogens, 0:03:05.406,0:03:09.047 including untreatable[br]panresistant infections. 0:03:09.862,0:03:12.132 Importantly, in contrast[br]to current antibiotics, 0:03:12.156,0:03:15.850 the frequency at which bacteria[br]develop resistance against halicin 0:03:15.874,0:03:17.358 is remarkably low. 0:03:18.303,0:03:23.013 We tested the ability of bacteria[br]to evolve resistance against halicin 0:03:23.037,0:03:24.825 as well as Cipro in the lab. 0:03:25.299,0:03:26.841 In the case of Cipro, 0:03:26.865,0:03:29.690 after just one day, we saw resistance. 0:03:30.213,0:03:31.691 In the case of halicin, 0:03:31.715,0:03:33.830 after one day,[br]we didn't see any resistance. 0:03:34.479,0:03:37.781 Amazingly, after even 30 days, 0:03:37.805,0:03:40.406 we didn't see any resistance[br]against halicin. 0:03:41.098,0:03:46.624 In this pilot project, we first tested[br]roughly 2,500 compounds against E. coli. 0:03:47.259,0:03:50.039 This training set included[br]known antibiotics, 0:03:50.063,0:03:51.809 such as Cipro and penicillin, 0:03:51.833,0:03:54.105 as well as many drugs[br]that are not antibiotics. 0:03:54.984,0:03:57.571 These data we used to train a model 0:03:57.595,0:04:01.573 to learn molecular features[br]associated with antibacterial activity. 0:04:02.269,0:04:04.970 We then applied this model[br]to a drug-repurposing library 0:04:04.994,0:04:07.472 consisting of several thousand molecules 0:04:07.496,0:04:10.114 and asked the model to identify molecules 0:04:10.138,0:04:12.922 that are predicted[br]to have antibacterial properties 0:04:12.946,0:04:15.419 but don't look like existing antibiotics. 0:04:16.427,0:04:21.224 Interestingly, only one molecule[br]in that library fit these criteria, 0:04:21.248,0:04:23.584 and that molecule[br]turned out to be halicin. 0:04:24.444,0:04:27.532 Given that halicin does not look[br]like any existing antibiotic, 0:04:27.556,0:04:31.710 it would have been impossible for a human,[br]including an antibiotic expert, 0:04:31.734,0:04:33.918 to identify halicin in this manner. 0:04:34.574,0:04:37.204 Imagine now what we could do[br]with this technology 0:04:37.228,0:04:38.969 against SARS-CoV-2. 0:04:39.783,0:04:41.148 And that's not all. 0:04:41.172,0:04:43.992 We're also using the tools[br]of synthetic biology, 0:04:44.016,0:04:46.627 tinkering with DNA[br]and other cellular machinery, 0:04:46.651,0:04:50.561 to serve human purposes[br]like combating COVID-19, 0:04:50.585,0:04:54.232 and of note, we are working[br]to develop a protective mask 0:04:54.256,0:04:57.688 that can also serve[br]as a rapid diagnostic test. 0:04:58.192,0:04:59.664 So how does that work? 0:04:59.688,0:05:00.893 Well, we recently showed 0:05:00.917,0:05:03.860 that you can take the cellular[br]machinery out of a living cell 0:05:03.884,0:05:07.976 and freeze-dry it along with[br]RNA sensors onto paper 0:05:08.000,0:05:12.916 in order to create low-cost[br]diagnostics for Ebola and Zika. 0:05:13.503,0:05:18.730 The sensors are activated when[br]they're rehydrated by a patient sample 0:05:18.754,0:05:21.576 that could consist of blood[br]or saliva, for example. 0:05:21.600,0:05:24.861 It turns out, this technology[br]is not limited to paper 0:05:24.885,0:05:27.771 and can be applied[br]to other materials, including cloth. 0:05:28.671,0:05:30.613 For the COVID-19 pandemic, 0:05:30.637,0:05:34.983 we're designing RNA sensors[br]to detect the virus 0:05:35.007,0:05:38.217 and freeze-drying these[br]along with the needed cellular machinery 0:05:38.241,0:05:40.948 into the fabric of a face mask, 0:05:40.972,0:05:43.201 where the simple act of breathing, 0:05:43.225,0:05:45.502 along with the water vapor[br]that comes with it, 0:05:45.526,0:05:47.286 can activate the test. 0:05:47.804,0:05:52.064 Thus, if a patient is infected[br]with SARS-CoV-2, 0:05:52.088,0:05:54.161 the mask will produce[br]a fluorescent signal 0:05:54.185,0:05:58.015 that could be detected by a simple,[br]inexpensive handheld device. 0:05:58.534,0:06:03.018 In one or two hours, a patient[br]could thus be diagnosed 0:06:03.042,0:06:06.014 safely, remotely and accurately. 0:06:06.735,0:06:09.255 We're also using synthetic biology 0:06:09.279,0:06:11.999 to design a candidate[br]vaccine for COVID-19. 0:06:13.014,0:06:15.667 We are repurposing the BCG vaccine, 0:06:15.691,0:06:18.561 which had been used against TB[br]for almost a century. 0:06:18.585,0:06:20.126 It's a live attenuated vaccine, 0:06:20.150,0:06:24.807 and we're engineering it[br]to express SARS-CoV-2 antigens, 0:06:24.831,0:06:27.645 which should trigger the production[br]of protective antibodies 0:06:27.669,0:06:29.304 by the immune system. 0:06:29.328,0:06:32.062 Importantly, BCG[br]is massively scalable 0:06:32.086,0:06:36.659 and has a safety profile that's among[br]the best of any reported vaccine. 0:06:37.881,0:06:42.986 With the tools of synthetic biology[br]and artificial intelligence, 0:06:43.010,0:06:46.358 we can win the fight[br]against this novel coronavirus. 0:06:46.844,0:06:50.163 This work is in its very early stages,[br]but the promise is real. 0:06:50.798,0:06:54.243 Science and technology[br]can give us an important advantage 0:06:54.267,0:06:57.428 in the battle of human wits[br]versus the genes of superbugs, 0:06:57.452,0:06:59.199 a battle we can win. 0:06:59.990,0:07:01.223 Thank you.