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