0:00:00.960,0:00:03.976 This is a tuberculosis ward, 0:00:04.000,0:00:07.816 and at the time this picture was taken[br]in the late 1800s, 0:00:07.840,0:00:10.456 one in seven of all people 0:00:10.480,0:00:12.240 died from tuberculosis. 0:00:12.680,0:00:15.440 We had no idea[br]what was causing this disease. 0:00:16.040,0:00:18.096 The hypothesis was actually 0:00:18.120,0:00:21.376 it was your constitution[br]that made you susceptible. 0:00:21.400,0:00:24.136 And it was a highly romanticized disease. 0:00:24.160,0:00:26.976 It was also called consumption, 0:00:27.000,0:00:30.136 and it was the disorder of poets 0:00:30.160,0:00:32.896 and artists and intellectuals. 0:00:32.920,0:00:36.656 And some people actually thought[br]it gave you heightened sensitivity 0:00:36.680,0:00:38.880 and conferred creative genius. 0:00:40.600,0:00:42.736 By the 1950s, 0:00:42.760,0:00:45.336 we instead knew[br]that tuberculosis was caused 0:00:45.360,0:00:48.736 by a highly contagious[br]bacterial infection, 0:00:48.760,0:00:50.936 which is slightly less romantic, 0:00:50.960,0:00:53.216 but that had the upside of us 0:00:53.240,0:00:56.576 being able to maybe[br]develop drugs to treat it. 0:00:56.600,0:00:59.616 So doctors had discovered[br]a new drug, Iproniazid, 0:00:59.640,0:01:03.016 that they were optimistic[br]might cure tuberculosis, 0:01:03.040,0:01:04.816 and they gave it to patients, 0:01:04.840,0:01:06.616 and patients were elated. 0:01:06.640,0:01:10.136 They were more social, more energetic. 0:01:10.160,0:01:12.776 One medical report actually says 0:01:12.800,0:01:14.760 they were "dancing in the halls." 0:01:15.400,0:01:17.016 And unfortunately, 0:01:17.040,0:01:19.760 this was not necessarily[br]because they were getting better. 0:01:20.320,0:01:22.520 A lot of them were still dying. 0:01:23.560,0:01:25.456 Another medical report describes them 0:01:25.480,0:01:30.160 as being "inappropriately happy." 0:01:31.120,0:01:34.720 And that is how the first[br]antidepressant was discovered. 0:01:35.880,0:01:39.936 So accidental discovery[br]is not uncommon in science, 0:01:39.960,0:01:43.096 but it requires more[br]than just a happy accident. 0:01:43.120,0:01:46.560 You have to be able to recognize it[br]for discovery to occur. 0:01:47.400,0:01:50.136 As a neuroscientist,[br]I'm going to talk to you a little bit 0:01:50.160,0:01:51.576 about my firsthand experience 0:01:51.600,0:01:54.816 with whatever you want to call[br]the opposite of dumb luck, 0:01:54.840,0:01:56.456 let's call it smart luck. 0:01:56.480,0:01:59.200 But first a bit more background. 0:02:00.360,0:02:03.016 Thankfully, since the 1950s, 0:02:03.040,0:02:07.016 we've developed some other drugs[br]and we can actually now cure tuberculosis. 0:02:07.040,0:02:10.696 And at least in the United States,[br]though not necessarily in other countries, 0:02:10.720,0:02:12.216 we have closed our sanitoriums 0:02:12.240,0:02:15.920 and probably most of you[br]are not too worried about TB. 0:02:16.800,0:02:19.456 But a lot of what was true[br]in the early 1900s 0:02:19.480,0:02:21.336 about infectious disease, 0:02:21.360,0:02:24.000 we can say now[br]about psychiatric disorders. 0:02:24.720,0:02:27.736 We are in the middle[br]of an epidemic of mood disorders 0:02:27.760,0:02:31.520 like depression and post-traumatic[br]stress disorder, or PTSD. 0:02:32.200,0:02:36.056 One in four of all adults[br]in the United States 0:02:36.080,0:02:37.560 suffers from mental illness, 0:02:38.080,0:02:41.216 which means that if you haven't[br]experienced personally 0:02:41.240,0:02:43.536 or someone in your family hasn't, 0:02:43.560,0:02:46.816 it's still very likely[br]that someone you know has, 0:02:46.840,0:02:48.480 though they may not talk about it. 0:02:50.120,0:02:53.416 Depression has actually now surpassed 0:02:53.440,0:02:58.296 HIV/AIDS, malaria, diabetes and war 0:02:58.320,0:03:01.576 as the leading cause[br]of disability worldwide. 0:03:01.600,0:03:05.216 And also, like tuberculosis in the 1950s, 0:03:05.240,0:03:07.296 we don't know what causes it. 0:03:07.320,0:03:09.256 Once it's developed, it's chronic, 0:03:09.280,0:03:10.776 lasts a lifetime, 0:03:10.800,0:03:13.120 and there are no known cures. 0:03:14.560,0:03:16.776 The second antidepressant we discovered, 0:03:16.800,0:03:19.256 also by accident in the 1950s, 0:03:19.280,0:03:22.480 from an antihistamine[br]that was making people manic, 0:03:23.760,0:03:24.960 Imipramine. 0:03:26.120,0:03:29.776 And in both the case of the tuberculosis[br]ward an the antihistamine, 0:03:29.800,0:03:31.496 someone had to be able to recognize 0:03:31.520,0:03:33.936 that a drug that was designed[br]to do one thing -- 0:03:33.960,0:03:36.536 treat tuberculosis[br]or suppress allergies -- 0:03:36.560,0:03:39.296 could be used to do[br]something very different -- 0:03:39.320,0:03:40.520 treat depression. 0:03:41.280,0:03:44.296 And this sort of repurposing[br]is actually quite challenging. 0:03:44.320,0:03:48.256 When doctors first saw[br]this mood-enhancing effect of Iproniazid, 0:03:48.280,0:03:50.736 they didn't really[br]recognize what they saw. 0:03:50.760,0:03:52.616 They were so used to thinking about it 0:03:52.640,0:03:55.416 from the framework[br]of being a tuberculosis drug 0:03:55.440,0:03:57.496 that they actually just listed it 0:03:57.520,0:04:00.296 as a side effect, an adverse side effect. 0:04:00.320,0:04:03.296 As you can see here,[br]a lot of these patients in 1954 0:04:03.320,0:04:05.520 are experiencing severe euphoria. 0:04:06.800,0:04:10.416 And they were worried[br]that this might somehow interfere 0:04:10.440,0:04:13.296 with their recovering from tuberculosis. 0:04:13.320,0:04:15.976 So they recommended that Iproniazid 0:04:16.000,0:04:19.576 only be used in cases of extreme TB 0:04:19.600,0:04:23.280 and in patients that were[br]highly emotionally stable, 0:04:24.120,0:04:28.016 which is of course the exact opposite[br]of how we use it as an antidepressant. 0:04:28.040,0:04:32.496 They were so used to looking at it[br]from the perspective of this one disease, 0:04:32.520,0:04:35.216 they could not see the larger implications 0:04:35.240,0:04:36.440 for another disease. 0:04:37.280,0:04:39.976 And to be fair,[br]it's not entirely their fault. 0:04:40.000,0:04:42.776 Functional fixedness[br]is a bias that affects all of us. 0:04:42.800,0:04:46.256 It's a tendency to only[br]be able to think of an object 0:04:46.280,0:04:48.880 in terms of its traditional[br]use or function. 0:04:49.640,0:04:51.536 And mental set is another thing. Right? 0:04:51.560,0:04:53.576 That's sort of this preconceived framework 0:04:53.600,0:04:55.376 with which we approach problems. 0:04:55.400,0:04:58.656 And that actually makes repurposing[br]pretty hard for all of us, 0:04:58.680,0:05:02.216 which is, I guess, why they gave[br]a TV show to the guy who was, 0:05:02.240,0:05:04.040 like, really great at repurposing. 0:05:04.560,0:05:06.440 (Laughter) 0:05:07.080,0:05:11.416 So the effects in both the case[br]of Iproniazid and Imipramine, 0:05:11.440,0:05:12.816 they were so strong -- 0:05:12.840,0:05:15.056 there was mania[br]or people dancing in the halls. 0:05:15.080,0:05:18.216 It's actually not that surprising[br]they were caught. 0:05:18.240,0:05:20.056 But it does make you wonder 0:05:20.080,0:05:21.720 what else we've missed. 0:05:22.920,0:05:25.096 So Iproniazid and Imipramine, 0:05:25.120,0:05:27.536 they're more than just[br]a case study in repurposing. 0:05:27.560,0:05:30.536 They have two other things in common[br]that are really important. 0:05:30.560,0:05:33.056 One, they have terrible side effects. 0:05:33.080,0:05:35.696 That includes liver toxicity, 0:05:35.720,0:05:38.696 weight gain of over 50 pounds, 0:05:38.720,0:05:40.496 suicidality. 0:05:40.520,0:05:44.696 And two, they both[br]increase levels of serotonin, 0:05:44.720,0:05:47.056 which is a chemical signal in the brain, 0:05:47.080,0:05:48.280 or a neurotransmitter. 0:05:49.280,0:05:51.776 And those two things together,[br]right, one or the two, 0:05:51.800,0:05:53.416 may not have been that important, 0:05:53.440,0:05:57.176 but the two together meant[br]that we had to develop safer drugs, 0:05:57.200,0:05:58.616 and that serotonin 0:05:58.640,0:06:00.720 seemed like a pretty good place to start. 0:06:01.560,0:06:05.456 So we developed drugs[br]to more specifically focus on serotonin, 0:06:05.480,0:06:09.136 the selective serotonin[br]reuptake inhibitors, so the SSRIs, 0:06:09.160,0:06:11.896 the most famous of which is Prozac. 0:06:11.920,0:06:13.896 And that was 30 years ago, 0:06:13.920,0:06:17.120 and since then we have mostly[br]just worked on optimizing those drugs. 0:06:17.640,0:06:20.856 And the SSRIs, they are better[br]than the drugs that came before them, 0:06:20.880,0:06:22.976 but they still have a lot of side effects, 0:06:23.000,0:06:25.896 including weight gain, insomnia, 0:06:25.920,0:06:27.120 suicidality, 0:06:28.000,0:06:30.336 and they take a really long time to work, 0:06:30.360,0:06:32.896 something like four to six weeks[br]in a lot of patients. 0:06:32.920,0:06:35.096 And that's in the patients[br]where they do work. 0:06:35.120,0:06:37.976 There are a lot of patients[br]where these drugs don't work. 0:06:38.000,0:06:41.376 And that means now, in 2016, 0:06:41.400,0:06:43.616 we still have no cures 0:06:43.640,0:06:45.216 for any mood disorders, 0:06:45.240,0:06:47.296 just drugs that suppress symptoms, 0:06:47.320,0:06:51.376 which is kind of the difference between[br]taking a painkiller for an infection 0:06:51.400,0:06:52.816 versus an antibiotic. 0:06:52.840,0:06:54.696 Painkiller will make you feel better, 0:06:54.720,0:06:57.800 but is not going to do anything[br]to treat that underlying disease. 0:06:58.600,0:07:00.936 And it was this flexibility[br]in our thinking 0:07:00.960,0:07:03.896 that let us recognize[br]that Iproniazid and Imipramine 0:07:03.920,0:07:06.016 could be repurposed in this way, 0:07:06.040,0:07:08.016 which led us to the serotonin hypothesis, 0:07:08.040,0:07:11.040 which we then, ironically, fixated on. 0:07:11.880,0:07:14.416 This is brain signaling, serotonin 0:07:14.440,0:07:15.696 from an SSRI commercial. 0:07:15.720,0:07:18.080 In case you're not clear,[br]this is a dramatization. 0:07:18.560,0:07:22.616 And in science, we try[br]and remove our bias, right, 0:07:22.640,0:07:25.016 by running double-blinded experiments 0:07:25.040,0:07:28.736 or being statistically agnostic[br]as to what our results will be. 0:07:28.760,0:07:31.216 But bias creeps in more insidiously 0:07:31.240,0:07:33.056 in what we choose to study 0:07:33.080,0:07:34.800 and how we choose to study it. 0:07:36.160,0:07:38.256 So we've focused on serotonin now 0:07:38.280,0:07:39.736 for the past 30 years, 0:07:39.760,0:07:42.000 often to the exclusion of other things. 0:07:42.760,0:07:44.120 We still have no cures, 0:07:45.080,0:07:48.496 and what if serotonin[br]isn't all there is to depression? 0:07:48.520,0:07:50.576 What if it's not even the key part of it? 0:07:50.600,0:07:52.776 That means no matter how much time 0:07:52.800,0:07:55.536 or money or effort we put into it, 0:07:55.560,0:07:57.480 it will never lead to a cure. 0:07:58.400,0:08:00.976 In the past few years,[br]doctors have discovered 0:08:01.000,0:08:05.920 probably what is the first truly new[br]antidepressant since the SSRIs, 0:08:06.440,0:08:07.736 Calypsol, 0:08:07.760,0:08:11.216 and this drug works very quickly,[br]within a few hours or a day, 0:08:11.240,0:08:13.136 and it doesn't work on serotonin. 0:08:13.160,0:08:15.840 It works on glutamate,[br]which is another neurotransmitter. 0:08:16.280,0:08:17.776 And it's also repurposed. 0:08:17.800,0:08:20.880 It was traditionally used[br]as anesthesia in surgery. 0:08:21.440,0:08:23.096 But unlike those other drugs, 0:08:23.120,0:08:24.936 which were recognized pretty quickly, 0:08:24.960,0:08:26.656 it took us 20 years 0:08:26.680,0:08:29.336 to realize that Calypsol[br]was an antidepressant, 0:08:29.360,0:08:32.216 despite the fact that it's actually[br]a better antidepressant, 0:08:32.240,0:08:33.856 probably, than those other drugs. 0:08:33.880,0:08:36.336 It's actually probably because of the fact 0:08:36.360,0:08:37.976 that it's a better antidepressant 0:08:38.000,0:08:39.895 that it was harder for us to recognize. 0:08:39.919,0:08:42.000 There was no mania to signal its effects. 0:08:42.480,0:08:45.576 So in 2013, up at Columbia University, 0:08:45.600,0:08:47.176 I was working with my colleague, 0:08:47.200,0:08:49.176 Dr. Christine Ann Denny, 0:08:49.200,0:08:53.000 and we were studying Calypsol[br]as an antidepressant in mice. 0:08:53.560,0:08:56.376 And Calypsol has, like,[br]a really short half-life, 0:08:56.400,0:08:59.456 which means it's out of your body[br]within a few hours. 0:08:59.480,0:09:00.896 And we were just piloting. 0:09:00.920,0:09:03.176 So we would give an injection to mice, 0:09:03.200,0:09:04.496 and then we'd wait a week, 0:09:04.520,0:09:07.200 and then we'd run[br]another experiment to save money. 0:09:07.920,0:09:10.056 And one of the experiments I was running, 0:09:10.080,0:09:11.736 we would stress the mice, 0:09:11.760,0:09:13.976 and we used that as a model of depression. 0:09:14.000,0:09:17.336 And at first it kind of just looked[br]like it didn't really work at all. 0:09:17.360,0:09:18.880 So we could have stopped there. 0:09:19.440,0:09:22.336 But I have run this model[br]of depression for years, 0:09:22.360,0:09:24.256 and the data just looked kind of weird. 0:09:24.280,0:09:26.136 It didn't really look right to me. 0:09:26.160,0:09:27.376 So I went back, 0:09:27.400,0:09:28.896 and we reanalyzed it 0:09:28.920,0:09:32.736 based on whether or not they had gotten[br]that one injection of Calypsol 0:09:32.760,0:09:33.960 a week beforehand. 0:09:34.840,0:09:36.856 And it looked kind of like this. 0:09:36.880,0:09:39.016 So if you look at the far left, 0:09:39.040,0:09:41.536 if you put a mouse in a new space, 0:09:41.560,0:09:43.816 this is the box, it's very exciting, 0:09:43.840,0:09:45.976 a mouse will walk around and explore, 0:09:46.000,0:09:50.296 and you can see that pink line[br]is actually the measure of them walking. 0:09:50.320,0:09:53.496 And we also give it[br]another mouse in a pencil cup 0:09:53.520,0:09:55.576 that it can decide to interact with. 0:09:55.600,0:09:58.816 This is also a dramatization,[br]in case that's not clear. 0:09:58.840,0:10:02.536 And a normal mouse will explore. 0:10:02.560,0:10:03.800 It will be social. 0:10:04.520,0:10:05.896 Check out what's going on. 0:10:05.920,0:10:08.816 If you stress a mouse[br]in this depression model, 0:10:08.840,0:10:10.120 which is the middle box, 0:10:11.000,0:10:12.896 they aren't social, they don't explore. 0:10:12.920,0:10:16.200 They mostly just kind of hide[br]in that back corner behind a cup. 0:10:16.920,0:10:20.016 Yet the mice that had gotten[br]that one injection of Calypsol 0:10:20.040,0:10:21.240 here on your right, 0:10:21.960,0:10:23.920 they were exploring, they were social. 0:10:24.640,0:10:27.120 They looked like they[br]had never been stressed at all, 0:10:27.920,0:10:29.120 which is impossible. 0:10:30.160,0:10:31.880 So we could have just stopped there, 0:10:32.680,0:10:36.976 but Christine had also used[br]Calypsol before as anesthesia, 0:10:37.000,0:10:38.576 and a few years ago she had seen 0:10:38.600,0:10:40.976 that it seemed to have[br]some weird effects on cells 0:10:41.000,0:10:42.216 and some other behavior 0:10:42.240,0:10:45.256 that also seemed to last[br]long after the drug, 0:10:45.280,0:10:46.536 maybe a few weeks. 0:10:46.560,0:10:47.816 So we were like, OK, 0:10:47.840,0:10:50.016 maybe this is not completely impossible, 0:10:50.040,0:10:51.536 but we were really skeptical. 0:10:51.560,0:10:54.096 So we did what you do in science[br]when you're not sure, 0:10:54.120,0:10:55.320 and we ran it again. 0:10:56.360,0:10:59.376 And I remember being in the animal room, 0:10:59.400,0:11:01.816 moving mice from box to box 0:11:01.840,0:11:03.056 to test them, 0:11:03.080,0:11:06.696 and Christine was actually sitting[br]on the floor with the computer in her lap 0:11:06.720,0:11:08.136 so the mice couldn't see her, 0:11:08.160,0:11:10.416 and she was analyzing[br]the data in real time. 0:11:10.440,0:11:11.816 And I remember us yelling, 0:11:11.840,0:11:15.136 which you're not supposed to do[br]in an animal room where you're testing 0:11:15.160,0:11:16.736 because it had worked. 0:11:16.760,0:11:21.136 It seemed like these mice[br]were protected against stress, 0:11:21.160,0:11:24.216 or they were inappropriately happy,[br]however you want to call it. 0:11:24.240,0:11:26.680 And we were really excited. 0:11:27.720,0:11:31.200 And then we were really skeptical,[br]because it was too good to be true. 0:11:31.760,0:11:32.960 So we ran it again. 0:11:33.640,0:11:36.376 And then we ran it again in a PTSD model, 0:11:36.400,0:11:38.816 and we ran it again[br]in a physiological model, 0:11:38.840,0:11:41.056 where all we did was give stress hormones. 0:11:41.080,0:11:42.696 And we had our undergrads run it. 0:11:42.720,0:11:46.840 And then we had our collaborators[br]halfway across the world in France run it. 0:11:47.680,0:11:50.896 And every time someone ran it,[br]they confirmed the same thing. 0:11:50.920,0:11:53.736 It seemed like[br]this one injection of Calypsol 0:11:53.760,0:11:56.520 was somehow protecting[br]against stress for weeks. 0:11:57.080,0:11:58.936 And we only published this a year ago, 0:11:58.960,0:12:03.040 but since then other labs[br]have independently confirmed this effect. 0:12:03.840,0:12:05.760 So we don't know what causes depression, 0:12:06.360,0:12:10.056 but we do know that stress[br]is the initial trigger 0:12:10.080,0:12:12.416 in 80 percent of cases, 0:12:12.440,0:12:14.656 and depression and PTSD[br]are different diseases, 0:12:14.680,0:12:16.696 but this is something[br]they share in common. 0:12:16.720,0:12:18.536 Right? It is traumatic stress 0:12:18.560,0:12:21.456 like active combat or natural disasters 0:12:21.480,0:12:23.936 or community violence or sexual assault 0:12:23.960,0:12:26.240 that causes post-traumatic[br]stress disorder, 0:12:26.880,0:12:29.960 and not everyone that is exposed to stress 0:12:30.640,0:12:32.496 develops a mood disorder. 0:12:32.520,0:12:35.416 And this ability to experience[br]stress and be resilient 0:12:35.440,0:12:39.600 and bounce back and not develop[br]depression or PTSD 0:12:40.400,0:12:42.656 is known as stress resilience, 0:12:42.680,0:12:44.536 and it varies between people. 0:12:44.560,0:12:47.896 And we have always thought of it[br]as just sort of this passive property. 0:12:47.920,0:12:50.456 It's the absence of susceptibility factors 0:12:50.480,0:12:52.560 and risk factors for these disorders. 0:12:53.520,0:12:55.400 But what if it were active? 0:12:56.320,0:12:57.816 Maybe we could enhance it, 0:12:57.840,0:13:00.000 sort of akin to putting on armor. 0:13:01.120,0:13:03.376 We had accidentally discovered 0:13:03.400,0:13:05.720 the first resilience-enhancing drug. 0:13:06.640,0:13:09.416 And like I said, we only gave[br]a tiny amount of the drug, 0:13:09.440,0:13:11.016 and it lasted for weeks, 0:13:11.040,0:13:14.256 and that's not like anything[br]you see with antidepressants. 0:13:14.280,0:13:18.600 But it is actually kind of similar[br]to what you see in immune vaccines. 0:13:19.080,0:13:22.016 So in immune vaccines,[br]you'll get your shots, 0:13:22.040,0:13:25.416 and then weeks, months, years later 0:13:25.440,0:13:27.776 when you're actually exposed to bacteria, 0:13:27.800,0:13:30.256 it's not the vaccine in your body[br]that protects you. 0:13:30.280,0:13:31.656 It's your own immune system 0:13:31.680,0:13:35.816 that's developed resistance and resilience[br]to this bacteria that fights it off, 0:13:35.840,0:13:37.976 and you actually never get the infection, 0:13:38.000,0:13:41.056 which is very different[br]from, say, our treatments. Right? 0:13:41.080,0:13:44.896 In that case, you get the infection,[br]you're exposed to the bacteria, 0:13:44.920,0:13:48.776 you're sick, and then you take,[br]say, an antibiotic which cures it, 0:13:48.800,0:13:52.040 and those drugs are actually working[br]to kill the bacteria. 0:13:52.680,0:13:55.176 Or similar to as I said before,[br]with this palliative, 0:13:55.200,0:13:58.056 you'll take something[br]that will suppress the symptoms, 0:13:58.080,0:14:00.776 but it won't treat[br]the underlying infection, 0:14:00.800,0:14:04.136 and you'll only feel better[br]during the time in which you're taking it, 0:14:04.160,0:14:06.096 which is why you have to keep taking it. 0:14:06.120,0:14:08.816 And in depression and PTSD -- 0:14:08.840,0:14:10.816 here we have your stress exposure -- 0:14:10.840,0:14:13.456 we only have palliative care. 0:14:13.480,0:14:15.976 Antidepressants only suppress symptoms, 0:14:16.000,0:14:18.856 and that is why you basically[br]have to keep taking them 0:14:18.880,0:14:20.576 for the life of the disease, 0:14:20.600,0:14:22.800 which is often[br]the length of your own life. 0:14:23.840,0:14:28.056 So we're calling our resilience[br]enhancing drugs "paravaccines," 0:14:28.080,0:14:29.616 which means vaccine-like, 0:14:29.640,0:14:32.136 because it seems[br]like they might have the potential 0:14:32.160,0:14:33.976 to protect against stress 0:14:34.000,0:14:37.416 and prevent mice from developing 0:14:37.440,0:14:40.200 depression and post-traumatic[br]stress disorder. 0:14:40.680,0:14:44.120 Also, not all antidepressants[br]are also paravaccines. 0:14:45.200,0:14:46.816 We tried Prozac as well, 0:14:46.840,0:14:48.200 and that had no effect. 0:14:48.960,0:14:51.976 So if this were to translate into humans, 0:14:52.000,0:14:54.576 we might be able to protect people 0:14:54.600,0:14:56.856 who are predictably at risk 0:14:56.880,0:15:00.736 against stress-induced disorders[br]like depression and PTSD. 0:15:00.760,0:15:03.896 So that's first responders[br]and firefighters, 0:15:03.920,0:15:08.056 refugees, prisoners and prison guards, 0:15:08.080,0:15:10.160 soldiers, you name it. 0:15:11.120,0:15:12.896 And to give you a sense 0:15:12.920,0:15:14.920 of the scale of these diseases, 0:15:15.520,0:15:18.576 in 2010, the global burden of disease 0:15:18.600,0:15:22.440 was estimated at 2.5 trillion dollars, 0:15:22.960,0:15:24.496 and since they are chronic, 0:15:24.520,0:15:27.736 that cost is compounding[br]and is therefore expected to rise 0:15:27.760,0:15:31.000 up to six trillion dollars[br]in just the next 15 years. 0:15:32.360,0:15:35.496 As I mentioned before,[br]repurposing can be challenging 0:15:35.520,0:15:38.040 because of our prior biases. 0:15:38.760,0:15:40.280 Calypsol has another name, 0:15:41.000,0:15:42.200 ketamine, 0:15:43.280,0:15:44.840 which also goes by another name, 0:15:45.360,0:15:46.776 Special K, 0:15:46.800,0:15:49.200 which is a club drug and drug of abuse. 0:15:50.440,0:15:53.536 It's still used across the world[br]as an anesthetic. 0:15:53.560,0:15:56.416 It's used in children.[br]We use it on the battlefield. 0:15:56.440,0:15:59.416 It's actually the drug of choice[br]in a lot of developing nations 0:15:59.440,0:16:01.296 because it doesn't affect breathing. 0:16:01.320,0:16:06.000 It is on the World Health Organization[br]list of most essential medicines. 0:16:06.480,0:16:10.040 If we had discovered ketamine[br]as a paravaccine first, 0:16:10.720,0:16:13.576 it'd be pretty easy for us to develop it, 0:16:13.600,0:16:17.456 but as is, we have to compete[br]with our functional fixedness 0:16:17.480,0:16:20.280 and mental set that kind of interfere. 0:16:21.600,0:16:25.456 Fortunately, it's not[br]the only compound we have discovered 0:16:25.480,0:16:28.920 that has these prophylactic,[br]paravaccine qualities, 0:16:29.600,0:16:31.800 but all of the other drugs[br]we've discovered, 0:16:32.680,0:16:34.856 or compounds if you will,[br]they're totally new, 0:16:34.880,0:16:38.496 they have to go through[br]the entire FDA approval process, 0:16:38.520,0:16:39.776 if they make it, 0:16:39.800,0:16:42.096 before they can ever be used in humans. 0:16:42.120,0:16:43.776 And that will be years. 0:16:43.800,0:16:46.056 So if we wanted something sooner, 0:16:46.080,0:16:48.456 ketamine is already FDA-approved. 0:16:48.480,0:16:51.176 It's generic, it's available. 0:16:51.200,0:16:55.360 We could develop it for a fraction[br]of the price and a fraction of the time. 0:16:56.280,0:16:59.376 But actually, beyond functional fixedness 0:16:59.400,0:17:00.656 and mental set, 0:17:00.680,0:17:04.256 there's a real other challenge[br]to repurposing drugs, 0:17:04.280,0:17:05.480 which is policy. 0:17:06.079,0:17:08.296 There are no incentives in place 0:17:08.319,0:17:12.056 once a drug is generic and off patent[br]and no longer exclusive 0:17:12.079,0:17:14.415 to encourage pharma companies[br]to develop them, 0:17:14.440,0:17:15.868 because they don't make money. 0:17:16.280,0:17:19.400 And that's not true for just ketamine.[br]That is true for all drugs. 0:17:20.480,0:17:26.136 Regardless, the idea itself[br]is completely novel in psychiatry, 0:17:26.160,0:17:30.056 to use drugs to prevent mental illness 0:17:30.080,0:17:31.440 as opposed to just treat it. 0:17:32.640,0:17:34.216 It is possible 0:17:34.240,0:17:37.696 that 20, 50, 100 years from now, 0:17:37.720,0:17:41.816 we will look back now[br]at depression and PTSD 0:17:41.840,0:17:45.056 the way we look back[br]at tuberculosis sanitoriums 0:17:45.080,0:17:46.280 as a thing of the past. 0:17:47.080,0:17:52.320 This could be the beginning of the end[br]of the mental health epidemic. 0:17:53.280,0:17:56.480 But as a great scientist once said, 0:17:57.800,0:18:00.056 only a fool is sure of anything. 0:18:00.080,0:18:02.120 A wise man keeps on guessing. 0:18:04.000,0:18:05.240 Thank you guys. 0:18:05.680,0:18:08.280 (Applause)