0:00:01.004,0:00:03.858 So how are we going to beat[br]this novel coronavirus? 0:00:04.091,0:00:06.950 By using our best tools: 0:00:07.217,0:00:09.585 our science and our technology. 0:00:09.802,0:00:12.989 In my lab, we're using[br]the tools of artificial intelligence 0:00:12.989,0:00:14.657 and synthetic biology 0:00:14.657,0:00:18.285 to speed up the fight[br]against this pandemic. 0:00:18.285,0:00:20.519 Our work was originally designed 0:00:20.519,0:00:23.089 to tackle the antibiotic[br]resistance crisis. 0:00:23.089,0:00:26.048 Our project seeks to harness[br]the power of machine learning 0:00:26.048,0:00:29.517 to replenish our antibiotic arsenal 0:00:29.517,0:00:33.120 and avoid a globally devastating[br]post-antibiotic era. 0:00:33.749,0:00:37.075 Importantly, the same technology[br]can be used to search 0:00:37.075,0:00:38.777 for antiviral compounds 0:00:38.777,0:00:41.512 that could help us fight[br]the current pandemic. 0:00:42.310,0:00:46.479 Machine learning is turning[br]the traditional model of drug discovery 0:00:46.479,0:00:47.529 on its head. 0:00:47.529,0:00:49.214 With this approach, 0:00:49.214,0:00:51.465 instead of painstakingly testing[br]thousands of existing molecules 0:00:51.465,0:00:53.217 one by one in a lab[br]for their effectiveness, 0:00:53.217,0:00:56.203 we can train a computer 0:00:56.203,0:01:00.430 to explore the exponentially larger space 0:01:00.430,0:01:04.435 of essentially all possible molecules[br]that could be synthesized, 0:01:04.435,0:01:10.014 and thus instead of looking[br]for a needle in a haystack, 0:01:10.014,0:01:13.783 we can use the giant magnet[br]of computing power 0:01:13.783,0:01:18.677 to find many needles[br]in multiple haystacks simultaneously. 0:01:18.677,0:01:20.462 We've already had some early success. 0:01:20.462,0:01:24.784 Recently, we used machine learning 0:01:24.784,0:01:28.076 to discover new antibiotics[br]that can help us fight off 0:01:28.076,0:01:32.547 the bacterial infections that can occur[br]alongside SARS-CoV-2 infections. 0:01:33.348,0:01:35.784 Two months ago, TED's Audacious Project 0:01:35.784,0:01:39.376 approved funding for us[br]to massively scale up our work 0:01:39.376,0:01:44.415 with the goal of discovering[br]seven new classes of antibiotics 0:01:44.415,0:01:47.384 against seven of the world's[br]deadly bacterial pathogens 0:01:47.992,0:01:50.528 over the next seven years. 0:01:50.731,0:01:52.428 For context, 0:01:52.428,0:01:55.071 the number of new class of antibiotics 0:01:55.071,0:01:58.290 that have been discovered[br]over the last three decades is zero. 0:01:58.404,0:02:01.927 While the quest for new antibiotics[br]is for our medium-term future, 0:02:01.927,0:02:06.435 the novel coronavirus[br]poses an immediate deadly threat, 0:02:06.602,0:02:10.388 and I'm excited to share that we think[br]we can use the same technology 0:02:10.388,0:02:13.548 to search for therapeutics[br]to fight this virus. 0:02:13.748,0:02:15.549 So how are we going to do it? 0:02:15.549,0:02:18.403 Well, we're creating[br]a compound training library, 0:02:18.403,0:02:21.644 and with collaborators[br]applying these molecules 0:02:21.644,0:02:23.957 to SARS-CoV-2-infected cells 0:02:23.957,0:02:28.398 to see which of them exhibit[br]effective activity. 0:02:28.398,0:02:31.538 These data will be use to train[br]a machine learning model 0:02:31.538,0:02:35.709 that will be applied to a [?][br]library of over a billion molecules 0:02:35.709,0:02:40.570 to search for potential[br]novel antiviral compounds. 0:02:40.570,0:02:43.289 We will synthesize and test[br]the top predictions 0:02:43.289,0:02:46.275 and advance the most promising[br]candidates into the clinic. 0:02:46.508,0:02:48.701 Sound too good to be true? 0:02:48.701,0:02:49.869 Well, it shouldn't. 0:02:49.869,0:02:53.276 The Antibiotics AI Project is founded[br]on our proof of concept research 0:02:53.276,0:02:56.674 that led to the discovery[br]of a novel broad spectrum antibiotic 0:02:56.674,0:02:57.859 called Halocin. 0:02:58.642,0:03:01.478 Halocin has potent antibacterial activity 0:03:01.478,0:03:05.615 against almost all antibiotic-resistant[br]bacterial pathogens, 0:03:05.801,0:03:09.442 including untreatable[br]pan-resistant infections. 0:03:09.942,0:03:12.211 Importantly, in contrast[br]to current antibiotics, 0:03:12.211,0:03:16.215 the frequency at which bacteria[br]develop resistance against Halocin 0:03:16.215,0:03:17.673 is remarkably low. 0:03:18.224,0:03:23.178 We tested the ability of bacteria[br]to evolve resistance against Halocin 0:03:23.178,0:03:25.299 as well as Cipro in the lab. 0:03:25.299,0:03:27.131 In the case of Cipro, 0:03:27.131,0:03:30.175 after just one day, we saw resistance. 0:03:30.391,0:03:31.960 In the case of Halocin, 0:03:31.960,0:03:34.646 after one day we didn't[br]see any resistance. 0:03:34.646,0:03:38.039 Amazingly, after even 30 days, 0:03:38.039,0:03:40.991 we didn't see any[br]resistance against Halocin. 0:03:41.242,0:03:46.980 In this pilot project, we first tested[br]roughly 2,500 compounds against E. coli. 0:03:47.213,0:03:50.273 This training set included[br]known antibiotics, 0:03:50.273,0:03:52.176 such as Cipro and penicillin, 0:03:52.176,0:03:55.127 as well as many drugs[br]that are not antibiotics. 0:03:55.294,0:03:57.904 These data we used to train a model 0:03:57.904,0:04:02.491 to learn molecular features[br]associated with antibacterial activity. 0:04:02.491,0:04:05.542 We then applied this model[br]to a drug repurposing library 0:04:05.995,0:04:08.187 consisting of several thousand molecules, 0:04:08.187,0:04:10.456 and asked the model to identify molecules 0:04:10.456,0:04:13.225 that are predicted[br]to have antibacterial properties 0:04:13.225,0:04:15.910 but don't look like existing antibiotics. 0:04:16.194,0:04:21.305 Interestingly, only one molecule[br]in that library fit these criteria, 0:04:21.506,0:04:24.342 and that molecule[br]turned out to be Halocin. 0:04:24.691,0:04:27.769 Given that Halocin does not look[br]like any existing antibiotic, 0:04:27.769,0:04:31.822 it would have been impossible for a human,[br]including an antibiotic expert, 0:04:31.822,0:04:34.724 to identify Halocin in this manner. 0:04:34.892,0:04:37.545 Imagine now what we could do[br]with this technology 0:04:37.545,0:04:40.053 against SARS-CoV-2. 0:04:40.053,0:04:43.106 And that's not all. 0:04:43.106,0:04:44.423 We're also using the tools[br]of synthetic biology, 0:04:44.423,0:04:46.893 tinkering with DNA[br]and other cellular machinery, 0:04:46.893,0:04:50.051 to serve human purposes[br]like combating COVID-19, 0:04:50.402,0:04:54.312 and at [??] we are working[br]to develop a protective mask 0:04:54.411,0:04:58.193 that can also serve[br]as a rapid diagnostic test. 0:04:58.414,0:04:59.945 So how does that work? 0:04:59.945,0:05:02.617 Well, we recently showed that you can take 0:05:02.617,0:05:04.360 the cellular machinery[br]out of a living cell 0:05:04.360,0:05:07.912 and freeze-dry it along with[br]RNA sensors onto paper 0:05:08.261,0:05:12.916 in order to create low-cost[br]diagnostics for Ebola and Zika. 0:05:13.750,0:05:18.429 The sensors are activated when[br]they're rehydrated by a patient sample 0:05:18.429,0:05:21.563 that could consist of blood[br]or saliva, for example. 0:05:21.781,0:05:25.040 It turns out this technology[br]is not limited to paper 0:05:25.040,0:05:28.894 and can be applied[br]to other materials, including cloth. 0:05:28.894,0:05:31.163 For the COVID-19 pandemic,[br]we're designing RNA sensors 0:05:31.163,0:05:33.014 to detect the virus 0:05:33.014,0:05:38.412 and freeze-drying these[br]along with the needed cellular machinery 0:05:38.412,0:05:40.561 into the fabric of a face mask, 0:05:40.561,0:05:42.851 where the simple act of breathing, 0:05:43.414,0:05:47.725 along with the water vapor[br]that comes with it, can activate the test. 0:05:48.043,0:05:51.496 Now, if the patient[br]is infected with SARS-CoV-2, 0:05:52.263,0:05:56.350 the mask will produce a fluorescent signal[br]that can be detected by a simple, 0:05:56.350,0:05:58.860 inexpensive handheld device. 0:05:58.860,0:06:01.111 In one or two hours, a patient[br]could those be diagnosed 0:06:01.111,0:06:06.339 safely, remotely and accurately. 0:06:07.006,0:06:10.349 We're also using synthetic biology 0:06:10.349,0:06:12.678 to design a candidate[br]vaccine for COVID-19. 0:06:12.912,0:06:15.830 We are repurposing the BCG vaccine, 0:06:15.830,0:06:18.975 which has been used against TB[br]for almost a century. 0:06:18.975,0:06:20.459 It's a live attenuated vaccine, 0:06:20.459,0:06:24.228 and we're engineering it[br]to express SARS-CoV-2 antigens, 0:06:24.777,0:06:27.829 which should trigger the production[br]of protective antibodies 0:06:27.829,0:06:29.649 by the immune system. 0:06:29.649,0:06:33.544 Importantly, BCG is massively scalable[br]and has a safety profile 0:06:33.544,0:06:37.012 that's among the best[br]of any reported vaccine. 0:06:38.096,0:06:43.224 With the tools of synthetic biology[br]and artificial intelligence, 0:06:43.224,0:06:46.611 we can win the fight[br]against this novel coronavirus. 0:06:46.844,0:06:50.354 This work is in its very early stages,[br]but the promise is real. 0:06:50.354,0:06:54.591 Science and technology[br]can give us an important advantage 0:06:54.591,0:06:57.695 in the battle of human wits[br]versus the genes of superbugs, 0:06:57.695,0:06:59.871 a battle we can win. 0:06:59.871,0:07:01.655 Thank you.