1 00:00:00,917 --> 00:00:03,825 So how are we going to beat this novel coronavirus? 2 00:00:04,317 --> 00:00:06,948 By using our best tools: 3 00:00:06,972 --> 00:00:09,011 our science and our technology. 4 00:00:09,594 --> 00:00:12,726 In my lab, we're using the tools of artificial intelligence 5 00:00:12,750 --> 00:00:14,329 and synthetic biology 6 00:00:14,353 --> 00:00:17,413 to speed up the fight against this pandemic. 7 00:00:18,078 --> 00:00:19,941 Our work was originally designed 8 00:00:19,965 --> 00:00:22,818 to tackle the antibiotic resistance crisis. 9 00:00:22,842 --> 00:00:27,531 Our project seeks to harness the power of machine learning 10 00:00:27,555 --> 00:00:29,401 to replenish our antibiotic arsenal 11 00:00:29,425 --> 00:00:33,263 and avoid a globally devastating postantibiotic era. 12 00:00:33,685 --> 00:00:36,505 Importantly, the same technology can be used 13 00:00:36,529 --> 00:00:38,601 to search for antiviral compounds 14 00:00:38,625 --> 00:00:41,303 that could help us fight the current pandemic. 15 00:00:42,080 --> 00:00:45,982 Machine learning is turning the traditional model of drug discovery 16 00:00:46,006 --> 00:00:47,410 on its head. 17 00:00:47,434 --> 00:00:48,659 With this approach, 18 00:00:48,683 --> 00:00:52,761 instead of painstakingly testing thousands of existing molecules 19 00:00:52,785 --> 00:00:54,221 one by one in a lab 20 00:00:54,245 --> 00:00:55,832 for their effectiveness, 21 00:00:55,856 --> 00:01:00,513 we can train a computer to explore the exponentially larger space 22 00:01:00,537 --> 00:01:04,121 of essentially all possible molecules that could be synthesized, 23 00:01:04,145 --> 00:01:09,759 and thus, instead of looking for a needle in a haystack, 24 00:01:09,783 --> 00:01:13,543 we can use the giant magnet of computing power 25 00:01:13,567 --> 00:01:17,482 to find many needles in multiple haystacks simultaneously. 26 00:01:18,423 --> 00:01:20,415 We've already had some early success. 27 00:01:21,010 --> 00:01:26,475 Recently, we used machine learning to discover new antibiotics 28 00:01:26,499 --> 00:01:29,059 that can help us fight off the bacterial infections 29 00:01:29,083 --> 00:01:32,694 that can occur alongside SARS-CoV-2 infections. 30 00:01:33,181 --> 00:01:37,350 Two months ago, TED's Audacious Project approved funding for us 31 00:01:37,374 --> 00:01:39,562 to massively scale up our work 32 00:01:39,586 --> 00:01:44,214 with the goal of discovering seven new classes of antibiotics 33 00:01:44,238 --> 00:01:47,721 against seven of the world's deadly bacterial pathogens 34 00:01:47,745 --> 00:01:49,800 over the next seven years. 35 00:01:50,206 --> 00:01:51,939 For context: 36 00:01:51,963 --> 00:01:53,891 the number of new class of antibiotics 37 00:01:53,915 --> 00:01:57,150 that have been discovered over the last three decades is zero. 38 00:01:58,030 --> 00:02:01,601 While the quest for new antibiotics is for our medium-term future, 39 00:02:01,625 --> 00:02:06,277 the novel coronavirus poses an immediate deadly threat, 40 00:02:06,301 --> 00:02:10,094 and I'm excited to share that we think we can use the same technology 41 00:02:10,118 --> 00:02:12,927 to search for therapeutics to fight this virus. 42 00:02:13,486 --> 00:02:15,205 So how are we going to do it? 43 00:02:15,229 --> 00:02:18,177 Well, we're creating a compound training library 44 00:02:18,201 --> 00:02:23,743 and with collaborators applying these molecules to SARS-CoV-2-infected cells 45 00:02:23,767 --> 00:02:27,661 to see which of them exhibit effective activity. 46 00:02:28,175 --> 00:02:31,367 These data will be use to train a machine learning model 47 00:02:31,391 --> 00:02:35,461 that will be applied to an in silico library of over a billion molecules 48 00:02:35,485 --> 00:02:39,689 to search for potential novel antiviral compounds. 49 00:02:40,324 --> 00:02:42,982 We will synthesize and test the top predictions 50 00:02:43,006 --> 00:02:45,895 and advance the most promising candidates into the clinic. 51 00:02:46,356 --> 00:02:48,134 Sound too good to be true? 52 00:02:48,158 --> 00:02:49,590 Well, it shouldn't. 53 00:02:49,614 --> 00:02:52,939 The Antibiotics AI Project is founded on our proof of concept research 54 00:02:52,963 --> 00:02:56,364 that led to the discovery of a novel broad-spectrum antibiotic 55 00:02:56,388 --> 00:02:57,573 called halicin. 56 00:02:58,443 --> 00:03:01,256 Halicin has potent antibacterial activity 57 00:03:01,280 --> 00:03:05,382 against almost all antibiotic-resistant bacterial pathogens, 58 00:03:05,406 --> 00:03:09,047 including untreatable panresistant infections. 59 00:03:09,862 --> 00:03:12,132 Importantly, in contrast to current antibiotics, 60 00:03:12,156 --> 00:03:15,850 the frequency at which bacteria develop resistance against halicin 61 00:03:15,874 --> 00:03:17,358 is remarkably low. 62 00:03:18,303 --> 00:03:23,013 We tested the ability of bacteria to evolve resistance against halicin 63 00:03:23,037 --> 00:03:24,825 as well as Cipro in the lab. 64 00:03:25,299 --> 00:03:26,841 In the case of Cipro, 65 00:03:26,865 --> 00:03:29,690 after just one day, we saw resistance. 66 00:03:30,213 --> 00:03:31,691 In the case of halicin, 67 00:03:31,715 --> 00:03:33,830 after one day, we didn't see any resistance. 68 00:03:34,479 --> 00:03:37,781 Amazingly, after even 30 days, 69 00:03:37,805 --> 00:03:40,406 we didn't see any resistance against halicin. 70 00:03:41,098 --> 00:03:46,624 In this pilot project, we first tested roughly 2,500 compounds against E. coli. 71 00:03:47,259 --> 00:03:50,039 This training set included known antibiotics, 72 00:03:50,063 --> 00:03:51,809 such as Cipro and penicillin, 73 00:03:51,833 --> 00:03:54,105 as well as many drugs that are not antibiotics. 74 00:03:54,984 --> 00:03:57,571 These data we used to train a model 75 00:03:57,595 --> 00:04:01,573 to learn molecular features associated with antibacterial activity. 76 00:04:02,269 --> 00:04:04,970 We then applied this model to a drug-repurposing library 77 00:04:04,994 --> 00:04:07,472 consisting of several thousand molecules 78 00:04:07,496 --> 00:04:10,114 and asked the model to identify molecules 79 00:04:10,138 --> 00:04:12,922 that are predicted to have antibacterial properties 80 00:04:12,946 --> 00:04:15,419 but don't look like existing antibiotics. 81 00:04:16,427 --> 00:04:21,224 Interestingly, only one molecule in that library fit these criteria, 82 00:04:21,248 --> 00:04:23,584 and that molecule turned out to be halicin. 83 00:04:24,444 --> 00:04:27,532 Given that halicin does not look like any existing antibiotic, 84 00:04:27,556 --> 00:04:31,710 it would have been impossible for a human, including an antibiotic expert, 85 00:04:31,734 --> 00:04:33,918 to identify halicin in this manner. 86 00:04:34,574 --> 00:04:37,204 Imagine now what we could do with this technology 87 00:04:37,228 --> 00:04:38,969 against SARS-CoV-2. 88 00:04:39,783 --> 00:04:41,148 And that's not all. 89 00:04:41,172 --> 00:04:43,992 We're also using the tools of synthetic biology, 90 00:04:44,016 --> 00:04:46,627 tinkering with DNA and other cellular machinery, 91 00:04:46,651 --> 00:04:50,561 to serve human purposes like combating COVID-19, 92 00:04:50,585 --> 00:04:54,232 and of note, we are working to develop a protective mask 93 00:04:54,256 --> 00:04:57,688 that can also serve as a rapid diagnostic test. 94 00:04:58,192 --> 00:04:59,664 So how does that work? 95 00:04:59,688 --> 00:05:00,893 Well, we recently showed 96 00:05:00,917 --> 00:05:03,860 that you can take the cellular machinery out of a living cell 97 00:05:03,884 --> 00:05:07,976 and freeze-dry it along with RNA sensors onto paper 98 00:05:08,000 --> 00:05:12,916 in order to create low-cost diagnostics for Ebola and Zika. 99 00:05:13,503 --> 00:05:18,730 The sensors are activated when they're rehydrated by a patient sample 100 00:05:18,754 --> 00:05:21,576 that could consist of blood or saliva, for example. 101 00:05:21,600 --> 00:05:24,861 It turns out, this technology is not limited to paper 102 00:05:24,885 --> 00:05:27,771 and can be applied to other materials, including cloth. 103 00:05:28,671 --> 00:05:30,613 For the COVID-19 pandemic, 104 00:05:30,637 --> 00:05:34,983 we're designing RNA sensors to detect the virus 105 00:05:35,007 --> 00:05:38,217 and freeze-drying these along with the needed cellular machinery 106 00:05:38,241 --> 00:05:40,948 into the fabric of a face mask, 107 00:05:40,972 --> 00:05:43,201 where the simple act of breathing, 108 00:05:43,225 --> 00:05:45,502 along with the water vapor that comes with it, 109 00:05:45,526 --> 00:05:47,286 can activate the test. 110 00:05:47,804 --> 00:05:52,064 Thus, if a patient is infected with SARS-CoV-2, 111 00:05:52,088 --> 00:05:54,161 the mask will produce a fluorescent signal 112 00:05:54,185 --> 00:05:58,015 that could be detected by a simple, inexpensive handheld device. 113 00:05:58,534 --> 00:06:03,018 In one or two hours, a patient could thus be diagnosed 114 00:06:03,042 --> 00:06:06,014 safely, remotely and accurately. 115 00:06:06,735 --> 00:06:09,255 We're also using synthetic biology 116 00:06:09,279 --> 00:06:11,999 to design a candidate vaccine for COVID-19. 117 00:06:13,014 --> 00:06:15,667 We are repurposing the BCG vaccine, 118 00:06:15,691 --> 00:06:18,561 which had been used against TB for almost a century. 119 00:06:18,585 --> 00:06:20,126 It's a live attenuated vaccine, 120 00:06:20,150 --> 00:06:24,807 and we're engineering it to express SARS-CoV-2 antigens, 121 00:06:24,831 --> 00:06:27,645 which should trigger the production of protective antibodies 122 00:06:27,669 --> 00:06:29,304 by the immune system. 123 00:06:29,328 --> 00:06:32,062 Importantly, BCG is massively scalable 124 00:06:32,086 --> 00:06:36,659 and has a safety profile that's among the best of any reported vaccine. 125 00:06:37,881 --> 00:06:42,986 With the tools of synthetic biology and artificial intelligence, 126 00:06:43,010 --> 00:06:46,358 we can win the fight against this novel coronavirus. 127 00:06:46,844 --> 00:06:50,163 This work is in its very early stages, but the promise is real. 128 00:06:50,798 --> 00:06:54,243 Science and technology can give us an important advantage 129 00:06:54,267 --> 00:06:57,428 in the battle of human wits versus the genes of superbugs, 130 00:06:57,452 --> 00:06:59,199 a battle we can win. 131 00:06:59,990 --> 00:07:01,223 Thank you.