WEBVTT 99:59:59.999 --> 99:59:59.999 So how are we going to beat this novel coronavirus? 99:59:59.999 --> 99:59:59.999 By using our best tools: 99:59:59.999 --> 99:59:59.999 our science and our technology. 99:59:59.999 --> 99:59:59.999 In my lab, we're using the tools of artificial intelligence 99:59:59.999 --> 99:59:59.999 and synthetic biology 99:59:59.999 --> 99:59:59.999 to speed up the fight against this pandemic. 99:59:59.999 --> 99:59:59.999 Our work was originally designed 99:59:59.999 --> 99:59:59.999 to tackle the antibiotic resistance crisis. 99:59:59.999 --> 99:59:59.999 Our project seeks to harness the power of machine learning 99:59:59.999 --> 99:59:59.999 to replenish our antibiotic arsenal 99:59:59.999 --> 99:59:59.999 and avoid a globally devastating post-antibiotic era. 99:59:59.999 --> 99:59:59.999 Importantly, the same technology can be used to search 99:59:59.999 --> 99:59:59.999 for antiviral compounds 99:59:59.999 --> 99:59:59.999 that could help us fight the current pandemic. 99:59:59.999 --> 99:59:59.999 Machine learning is turning the traditional model of drug discovery 99:59:59.999 --> 99:59:59.999 on its head. 99:59:59.999 --> 99:59:59.999 With this approach, 99:59:59.999 --> 99:59:59.999 instead of painstakingly testing thousands of existing molecules 99:59:59.999 --> 99:59:59.999 one by one in a lab for their effectiveness, 99:59:59.999 --> 99:59:59.999 we can train a computer 99:59:59.999 --> 99:59:59.999 to explore the exponentially larger space 99:59:59.999 --> 99:59:59.999 of essentially all possible molecules that could be synthesized, 99:59:59.999 --> 99:59:59.999 and thus instead of looking for a needle in a haystack, 99:59:59.999 --> 99:59:59.999 we can use the giant magnet of computing power 99:59:59.999 --> 99:59:59.999 to find many needles in multiple haystacks simultaneously. 99:59:59.999 --> 99:59:59.999 We've already had some early success. 99:59:59.999 --> 99:59:59.999 Recently, we used machine learning 99:59:59.999 --> 99:59:59.999 to discover new antibiotics that can help us fight off 99:59:59.999 --> 99:59:59.999 the bacterial infections that can occur alongside SARS-CoV-2 infections. 99:59:59.999 --> 99:59:59.999 Two months ago, TED's Audacious Project 99:59:59.999 --> 99:59:59.999 approved funding for us to massively scale up our work 99:59:59.999 --> 99:59:59.999 with the goal of discovering seven new classes of antibiotics 99:59:59.999 --> 99:59:59.999 against seven of the world's deadly bacterial pathogens 99:59:59.999 --> 99:59:59.999 over the next seven years. 99:59:59.999 --> 99:59:59.999 For context, 99:59:59.999 --> 99:59:59.999 the number of new class of antibiotics 99:59:59.999 --> 99:59:59.999 that have been discovered over the last three decades is zero. 99:59:59.999 --> 99:59:59.999 While the quest for new antibiotics is for our medium-term future, 99:59:59.999 --> 99:59:59.999 the novel coronavirus poses an immediate deadly threat, 99:59:59.999 --> 99:59:59.999 and I'm excited to share that we think we can use the same technology 99:59:59.999 --> 99:59:59.999 to search for therapeutics to fight this virus. 99:59:59.999 --> 99:59:59.999 So how are we going to do it? 99:59:59.999 --> 99:59:59.999 Well, we're creating a compound training library, 99:59:59.999 --> 99:59:59.999 and with collaborators applying these molecules 99:59:59.999 --> 99:59:59.999 to SARS-CoV-2-infected cells 99:59:59.999 --> 99:59:59.999 to see which of them exhibit effective activity. 99:59:59.999 --> 99:59:59.999 These data will be use to train a machine learning model 99:59:59.999 --> 99:59:59.999 that will be applied to a [?] library of over a billion molecules 99:59:59.999 --> 99:59:59.999 to search for potential novel antiviral compounds. 99:59:59.999 --> 99:59:59.999 We will synthesize and test the top predictions 99:59:59.999 --> 99:59:59.999 and advance the most promising candidates into the clinic. 99:59:59.999 --> 99:59:59.999 Sound too good to be true? 99:59:59.999 --> 99:59:59.999 Well, it shouldn't. 99:59:59.999 --> 99:59:59.999 The Antibiotics AI Project is founded on our proof of concept research 99:59:59.999 --> 99:59:59.999 that led to the discovery of a novel broad spectrum antibiotic 99:59:59.999 --> 99:59:59.999 called Halocin. 99:59:59.999 --> 99:59:59.999 Halocin has potent antibacterial activity 99:59:59.999 --> 99:59:59.999 against almost all antibiotic-resistant bacterial pathogens, 99:59:59.999 --> 99:59:59.999 including untreatable pan-resistant infections. 99:59:59.999 --> 99:59:59.999 Importantly, in contrast to current antibiotics, 99:59:59.999 --> 99:59:59.999 the frequency at which bacteria develop resistance against Halocin 99:59:59.999 --> 99:59:59.999 is remarkably low. 99:59:59.999 --> 99:59:59.999 We tested the ability of bacteria to evolve resistance against Halocin 99:59:59.999 --> 99:59:59.999 as well as Cipro in the lab. 99:59:59.999 --> 99:59:59.999 In the case of Cipro, 99:59:59.999 --> 99:59:59.999 after just one day, we saw resistance. 99:59:59.999 --> 99:59:59.999 In the case of Halocin, 99:59:59.999 --> 99:59:59.999 after one day we didn't see any resistance. 99:59:59.999 --> 99:59:59.999 Amazingly, after even 30 days, 99:59:59.999 --> 99:59:59.999 we didn't see any resistance against Halocin. 99:59:59.999 --> 99:59:59.999 In this pilot project, we first tested roughly 2,500 compounds against E. coli. 99:59:59.999 --> 99:59:59.999 This training set included known antibiotics, 99:59:59.999 --> 99:59:59.999 such as Cipro and penicillin, 99:59:59.999 --> 99:59:59.999 as well as many drugs that are not antibiotics. 99:59:59.999 --> 99:59:59.999 These data we used to train a model 99:59:59.999 --> 99:59:59.999 to learn molecular features associated with antibacterial activity. 99:59:59.999 --> 99:59:59.999 We then applied this model to a drug repurposing library 99:59:59.999 --> 99:59:59.999 consisting of several thousand molecules, 99:59:59.999 --> 99:59:59.999 and asked the model to identify molecules 99:59:59.999 --> 99:59:59.999 that are predicted to have antibacterial properties 99:59:59.999 --> 99:59:59.999 but don't look like existing antibiotics. 99:59:59.999 --> 99:59:59.999 Interestingly, only one molecule in that library fit these criteria, 99:59:59.999 --> 99:59:59.999 and that molecule turned out to be Halocin. 99:59:59.999 --> 99:59:59.999 Given that Halocin does not look like any existing antibiotic, 99:59:59.999 --> 99:59:59.999 it would have been impossible for a human, including an antibiotic expert, 99:59:59.999 --> 99:59:59.999 to identify Halocin in this manner. 99:59:59.999 --> 99:59:59.999 Imagine now what we could do with this technology 99:59:59.999 --> 99:59:59.999 against SARS-CoV-2. 99:59:59.999 --> 99:59:59.999 And that's not all. 99:59:59.999 --> 99:59:59.999 We're also using the tools of synthetic biology, 99:59:59.999 --> 99:59:59.999 tinkering with DNA and other cellular machinery, to serve human purposes like combating COVID-19 [??] we are working to develop a protective mask that can also serve as a rapid diagnostic test. How does that work? Well, we recently showed that you can take the cellular machinery out of a living cell and freeze-dry it along with RNA sensors onto paper in order to create low-cost diagnostics for Ebola and Zika. The sensors are activated when they're rehydrated by a patient sample that could consist of blood or saliva, for example. It turns out this technology is not limited to paper and can be applied to other materials, including cloth. For the COVID-19 pandemic, we're designing RNA sensors to detect the virus and freeze-drying these along with the needed cellular machinery into the fabric of a face mask, where the simple act of breathing, along with the water vapor that comes with it, can activate the test. Now, if the patient is infected with SARS-CoV-2, the mask will produce a fluorescent signal that can be detected by a simple, inexpensive handheld device. In one or two hours, a patient could those be diagnosed safely, remotely and accurately. We're also using synthetic biology to design a candidate vaccine for COVID-19. We are repurposing the BCG vaccine, which has been used against TB for almost a century. It's a live attenuated vaccine, and we're engineering it to express SARS-CoV-2 antigens, which should trigger the production of protective antibodies by the immune system. Importantly, BCG is massively scalable and has a safety profile that's among the best of any reported vaccine. With the tools of synthetic biology and artificial intelligence, we can win the fight against this novel coronavirus. This work is in its very early stages, but the promise is real. Science and technology can give us an important advantage in the battle of human wits versus the genes of superbugs, a battle we can win. Thank you.