1 00:00:01,004 --> 00:00:03,858 So how are we going to beat this novel coronavirus? 2 00:00:04,091 --> 00:00:06,950 By using our best tools: 3 00:00:07,217 --> 00:00:09,585 our science and our technology. 4 00:00:09,802 --> 00:00:12,989 In my lab, we're using the tools of artificial intelligence 5 00:00:12,989 --> 00:00:14,657 and synthetic biology 6 00:00:14,657 --> 00:00:18,285 to speed up the fight against this pandemic. 7 00:00:18,285 --> 00:00:20,519 Our work was originally designed 8 00:00:20,519 --> 00:00:23,089 to tackle the antibiotic resistance crisis. 9 00:00:23,089 --> 00:00:26,048 Our project seeks to harness the power of machine learning 10 00:00:26,048 --> 00:00:29,517 to replenish our antibiotic arsenal 11 00:00:29,517 --> 00:00:33,120 and avoid a globally devastating post-antibiotic era. 12 00:00:33,749 --> 00:00:37,075 Importantly, the same technology can be used to search 13 00:00:37,075 --> 00:00:38,777 for antiviral compounds 14 00:00:38,777 --> 00:00:41,512 that could help us fight the current pandemic. 15 00:00:42,310 --> 00:00:46,479 Machine learning is turning the traditional model of drug discovery 16 00:00:46,479 --> 00:00:47,529 on its head. 17 00:00:47,529 --> 00:00:49,214 With this approach, 18 00:00:49,214 --> 00:00:51,465 instead of painstakingly testing thousands of existing molecules 19 00:00:51,465 --> 00:00:53,217 one by one in a lab for their effectiveness, 20 00:00:53,217 --> 00:00:56,203 we can train a computer 21 00:00:56,203 --> 00:01:00,430 to explore the exponentially larger space 22 00:01:00,430 --> 00:01:04,435 of essentially all possible molecules that could be synthesized, 23 00:01:04,435 --> 00:01:10,014 and thus instead of looking for a needle in a haystack, 24 00:01:10,014 --> 00:01:13,783 we can use the giant magnet of computing power 25 00:01:13,783 --> 00:01:18,677 to find many needles in multiple haystacks simultaneously. 26 00:01:18,677 --> 00:01:20,462 We've already had some early success. 27 00:01:20,462 --> 00:01:24,784 Recently, we used machine learning 28 00:01:24,784 --> 00:01:28,076 to discover new antibiotics that can help us fight off 29 00:01:28,076 --> 00:01:32,547 the bacterial infections that can occur alongside SARS-CoV-2 infections. 30 00:01:33,348 --> 00:01:35,784 Two months ago, TED's Audacious Project 31 00:01:35,784 --> 00:01:39,376 approved funding for us to massively scale up our work 32 00:01:39,376 --> 00:01:44,415 with the goal of discovering seven new classes of antibiotics 33 00:01:44,415 --> 00:01:47,384 against seven of the world's deadly bacterial pathogens 34 00:01:47,992 --> 00:01:50,528 over the next seven years. 35 00:01:50,731 --> 00:01:52,428 For context, 36 00:01:52,428 --> 00:01:55,071 the number of new class of antibiotics 37 00:01:55,071 --> 00:01:58,290 that have been discovered over the last three decades is zero. 38 00:01:58,404 --> 00:02:01,927 While the quest for new antibiotics is for our medium-term future, 39 00:02:01,927 --> 00:02:06,435 the novel coronavirus poses an immediate deadly threat, 40 00:02:06,602 --> 00:02:10,388 and I'm excited to share that we think we can use the same technology 41 00:02:10,388 --> 00:02:13,548 to search for therapeutics to fight this virus. 42 00:02:13,748 --> 00:02:15,549 So how are we going to do it? 43 00:02:15,549 --> 00:02:18,403 Well, we're creating a compound training library, 44 00:02:18,403 --> 00:02:21,644 and with collaborators applying these molecules 45 00:02:21,644 --> 00:02:23,957 to SARS-CoV-2-infected cells 46 00:02:23,957 --> 00:02:28,398 to see which of them exhibit effective activity. 47 00:02:28,398 --> 00:02:31,538 These data will be use to train a machine learning model 48 00:02:31,538 --> 00:02:35,709 that will be applied to a [?] library of over a billion molecules 49 00:02:35,709 --> 00:02:40,570 to search for potential novel antiviral compounds. 50 00:02:40,570 --> 00:02:43,289 We will synthesize and test the top predictions 51 00:02:43,289 --> 00:02:46,275 and advance the most promising candidates into the clinic. 52 00:02:46,508 --> 00:02:48,701 Sound too good to be true? 53 00:02:48,701 --> 00:02:49,869 Well, it shouldn't. 54 00:02:49,869 --> 00:02:53,276 The Antibiotics AI Project is founded on our proof of concept research 55 00:02:53,276 --> 00:02:56,674 that led to the discovery of a novel broad spectrum antibiotic 56 00:02:56,674 --> 00:02:57,859 called Halocin. 57 00:02:58,642 --> 00:03:01,478 Halocin has potent antibacterial activity 58 00:03:01,478 --> 00:03:05,615 against almost all antibiotic-resistant bacterial pathogens, 59 00:03:05,801 --> 00:03:09,442 including untreatable pan-resistant infections. 60 00:03:09,942 --> 00:03:12,211 Importantly, in contrast to current antibiotics, 61 00:03:12,211 --> 00:03:16,215 the frequency at which bacteria develop resistance against Halocin 62 00:03:16,215 --> 00:03:17,673 is remarkably low. 63 00:03:18,224 --> 00:03:23,178 We tested the ability of bacteria to evolve resistance against Halocin 64 00:03:23,178 --> 00:03:25,299 as well as Cipro in the lab. 65 00:03:25,299 --> 00:03:27,131 In the case of Cipro, 66 00:03:27,131 --> 00:03:30,175 after just one day, we saw resistance. 67 00:03:30,391 --> 00:03:31,960 In the case of Halocin, 68 00:03:31,960 --> 00:03:34,646 after one day we didn't see any resistance. 69 00:03:34,646 --> 00:03:38,039 Amazingly, after even 30 days, 70 00:03:38,039 --> 00:03:40,991 we didn't see any resistance against Halocin. 71 00:03:41,242 --> 00:03:46,980 In this pilot project, we first tested roughly 2,500 compounds against E. coli. 72 00:03:47,213 --> 00:03:50,273 This training set included known antibiotics, 73 00:03:50,273 --> 00:03:52,176 such as Cipro and penicillin, 74 00:03:52,176 --> 00:03:55,127 as well as many drugs that are not antibiotics. 75 00:03:55,294 --> 00:03:57,904 These data we used to train a model 76 00:03:57,904 --> 00:04:02,491 to learn molecular features associated with antibacterial activity. 77 00:04:02,491 --> 00:04:05,542 We then applied this model to a drug repurposing library 78 00:04:05,995 --> 00:04:08,187 consisting of several thousand molecules, 79 00:04:08,187 --> 00:04:10,456 and asked the model to identify molecules 80 00:04:10,456 --> 00:04:13,225 that are predicted to have antibacterial properties 81 00:04:13,225 --> 00:04:15,910 but don't look like existing antibiotics. 82 00:04:16,194 --> 00:04:21,305 Interestingly, only one molecule in that library fit these criteria, 83 00:04:21,506 --> 00:04:24,342 and that molecule turned out to be Halocin. 84 00:04:24,691 --> 00:04:27,769 Given that Halocin does not look like any existing antibiotic, 85 00:04:27,769 --> 00:04:31,822 it would have been impossible for a human, including an antibiotic expert, 86 00:04:31,822 --> 00:04:34,724 to identify Halocin in this manner. 87 00:04:34,892 --> 00:04:37,545 Imagine now what we could do with this technology 88 00:04:37,545 --> 00:04:40,053 against SARS-CoV-2. 89 00:04:40,053 --> 00:04:43,106 And that's not all. 90 00:04:43,106 --> 00:04:44,423 We're also using the tools of synthetic biology, 91 00:04:44,423 --> 00:04:46,893 tinkering with DNA and other cellular machinery, 92 00:04:46,893 --> 00:04:50,051 to serve human purposes like combating COVID-19, 93 00:04:50,402 --> 00:04:54,312 and at [??] we are working to develop a protective mask 94 00:04:54,411 --> 00:04:58,193 that can also serve as a rapid diagnostic test. 95 00:04:58,414 --> 00:04:59,945 So how does that work? 96 00:04:59,945 --> 00:05:02,617 Well, we recently showed that you can take 97 00:05:02,617 --> 00:05:04,360 the cellular machinery out of a living cell 98 00:05:04,360 --> 00:05:07,912 and freeze-dry it along with RNA sensors onto paper 99 00:05:08,261 --> 00:05:12,916 in order to create low-cost diagnostics for Ebola and Zika. 100 00:05:13,750 --> 00:05:18,429 The sensors are activated when they're rehydrated by a patient sample 101 00:05:18,429 --> 00:05:21,563 that could consist of blood or saliva, for example. 102 00:05:21,781 --> 00:05:25,040 It turns out this technology is not limited to paper 103 00:05:25,040 --> 00:05:28,894 and can be applied to other materials, including cloth. 104 00:05:28,894 --> 00:05:31,163 For the COVID-19 pandemic, we're designing RNA sensors 105 00:05:31,163 --> 00:05:33,014 to detect the virus 106 00:05:33,014 --> 00:05:38,412 and freeze-drying these along with the needed cellular machinery 107 00:05:38,412 --> 00:05:40,561 into the fabric of a face mask, 108 00:05:40,561 --> 00:05:42,851 where the simple act of breathing, 109 00:05:43,414 --> 00:05:47,725 along with the water vapor that comes with it, can activate the test. 110 00:05:48,043 --> 00:05:51,496 Now, if the patient is infected with SARS-CoV-2, 111 00:05:52,263 --> 00:05:56,350 the mask will produce a fluorescent signal that can be detected by a simple, 112 00:05:56,350 --> 00:05:58,860 inexpensive handheld device. 113 00:05:58,860 --> 00:06:01,111 In one or two hours, a patient could those be diagnosed 114 00:06:01,111 --> 00:06:06,339 safely, remotely and accurately. 115 00:06:07,006 --> 00:06:10,349 We're also using synthetic biology 116 00:06:10,349 --> 00:06:12,678 to design a candidate vaccine for COVID-19. 117 00:06:12,912 --> 00:06:15,830 We are repurposing the BCG vaccine, 118 00:06:15,830 --> 00:06:18,975 which has been used against TB for almost a century. 119 00:06:18,975 --> 00:06:20,459 It's a live attenuated vaccine, 120 00:06:20,459 --> 00:06:24,228 and we're engineering it to express SARS-CoV-2 antigens, 121 00:06:24,777 --> 00:06:27,829 which should trigger the production of protective antibodies 122 00:06:27,829 --> 00:06:29,649 by the immune system. 123 00:06:29,649 --> 00:06:33,544 Importantly, BCG is massively scalable and has a safety profile 124 00:06:33,544 --> 00:06:37,012 that's among the best of any reported vaccine. 125 00:06:38,096 --> 00:06:43,224 With the tools of synthetic biology and artificial intelligence, 126 00:06:43,224 --> 00:06:46,611 we can win the fight against this novel coronavirus. 127 00:06:46,844 --> 00:06:50,354 This work is in its very early stages, but the promise is real. 128 00:06:50,354 --> 00:06:54,591 Science and technology can give us an important advantage 129 00:06:54,591 --> 00:06:57,695 in the battle of human wits versus the genes of superbugs, 130 00:06:57,695 --> 00:06:59,871 a battle we can win. 131 00:06:59,871 --> 00:07:01,655 Thank you.