0:00:01.060,0:00:04.075 This is a tuberculosis ward, 0:00:04.100,0:00:07.916 and at the time this picture was taken[br]in the late 1800s, 0:00:07.939,0:00:10.556 one in seven of all people 0:00:10.580,0:00:12.340 died from tuberculosis. 0:00:12.780,0:00:15.540 We had no idea[br]what was causing this disease. 0:00:16.140,0:00:18.196 The hypothesis was actually 0:00:18.220,0:00:21.476 it was your constitution[br]that made you susceptible. 0:00:21.500,0:00:24.236 And it was a highly romanticized disease. 0:00:24.260,0:00:27.076 It was also called consumption, 0:00:27.100,0:00:30.236 and it was the disorder of poets 0:00:30.260,0:00:32.996 and artists and intellectuals. 0:00:33.020,0:00:36.756 And some people actually thought[br]it gave you heightened sensitivity 0:00:36.780,0:00:38.980 and conferred creative genius. 0:00:40.700,0:00:42.836 By the 1950s, 0:00:42.860,0:00:45.436 we instead knew[br]that tuberculosis was caused 0:00:45.460,0:00:48.836 by a highly contagious[br]bacterial infection, 0:00:48.860,0:00:51.036 which is slightly less romantic, 0:00:51.060,0:00:53.316 but that had the upside 0:00:53.340,0:00:56.676 of us being able to maybe[br]develop drugs to treat it. 0:00:56.700,0:00:59.716 So doctors had discovered[br]a new drug, iproniazid, 0:00:59.740,0:01:03.116 that they were optimistic[br]might cure tuberculosis, 0:01:03.140,0:01:04.916 and they gave it to patients, 0:01:04.940,0:01:06.716 and patients were elated. 0:01:06.740,0:01:10.236 They were more social, more energetic. 0:01:10.260,0:01:14.860 One medical report actually says[br]they were "dancing in the halls." 0:01:15.500,0:01:17.116 And unfortunately, 0:01:17.140,0:01:19.860 this was not necessarily[br]because they were getting better. 0:01:20.420,0:01:22.620 A lot of them were still dying. 0:01:23.660,0:01:30.260 Another medical report describes them[br]as being "inappropriately happy." 0:01:31.220,0:01:34.820 And that is how the first[br]antidepressant was discovered. 0:01:35.980,0:01:40.036 So accidental discovery[br]is not uncommon in science, 0:01:40.060,0:01:43.196 but it requires more[br]than just a happy accident. 0:01:43.220,0:01:46.660 You have to be able to recognize it[br]for discovery to occur. 0:01:47.500,0:01:50.236 As a neuroscientist,[br]I'm going to talk to you a little bit 0:01:50.260,0:01:51.676 about my firsthand experience 0:01:51.700,0:01:54.916 with whatever you want to call[br]the opposite of dumb luck -- 0:01:54.940,0:01:56.556 let's call it smart luck. 0:01:56.580,0:01:59.300 But first, a bit more background. 0:02:00.460,0:02:03.116 Thankfully, since the 1950s, 0:02:03.140,0:02:07.116 we've developed some other drugs[br]and we can actually now cure tuberculosis. 0:02:07.140,0:02:10.795 And at least in the United States,[br]though not necessarily in other countries, 0:02:10.820,0:02:12.316 we have closed our sanitoriums 0:02:12.340,0:02:16.020 and probably most of you[br]are not too worried about TB. 0:02:16.900,0:02:19.556 But a lot of what was true[br]in the early 1900s 0:02:19.580,0:02:21.436 about infectious disease, 0:02:21.460,0:02:24.100 we can say now[br]about psychiatric disorders. 0:02:24.820,0:02:27.836 We are in the middle[br]of an epidemic of mood disorders 0:02:27.860,0:02:31.620 like depression and post-traumatic[br]stress disorder, or PTSD. 0:02:32.300,0:02:36.156 One in four of all adults[br]in the United States 0:02:36.180,0:02:37.660 suffers from mental illness, 0:02:38.180,0:02:41.316 which means that if you haven't[br]experienced it personally 0:02:41.340,0:02:43.636 or someone in your family hasn't, 0:02:43.660,0:02:46.916 it's still very likely[br]that someone you know has, 0:02:46.940,0:02:48.580 though they may not talk about it. 0:02:50.220,0:02:53.516 Depression has actually now surpassed 0:02:53.540,0:02:58.396 HIV/AIDS, malaria, diabetes and war 0:02:58.420,0:03:01.676 as the leading cause[br]of disability worldwide. 0:03:01.700,0:03:05.316 And also, like tuberculosis in the 1950s, 0:03:05.340,0:03:07.396 we don't know what causes it. 0:03:07.420,0:03:09.356 Once it's developed, it's chronic, 0:03:09.380,0:03:10.876 lasts a lifetime, 0:03:10.900,0:03:13.220 and there are no known cures. 0:03:14.660,0:03:16.876 The second antidepressant we discovered, 0:03:16.900,0:03:19.356 also by accident, in the 1950s, 0:03:19.380,0:03:22.580 from an antihistamine[br]that was making people manic, 0:03:23.860,0:03:25.060 imipramine. 0:03:26.220,0:03:29.876 And in both the case of the tuberculosis[br]ward and the antihistamine, 0:03:29.900,0:03:31.596 someone had to be able to recognize 0:03:31.620,0:03:34.036 that a drug that was designed[br]to do one thing -- 0:03:34.060,0:03:36.636 treat tuberculosis[br]or suppress allergies -- 0:03:36.660,0:03:39.396 could be used to do[br]something very different -- 0:03:39.420,0:03:40.620 treat depression. 0:03:41.380,0:03:44.396 And this sort of repurposing[br]is actually quite challenging. 0:03:44.420,0:03:48.356 When doctors first saw[br]this mood-enhancing effect of iproniazid, 0:03:48.380,0:03:50.836 they didn't really recognize[br]what they saw. 0:03:50.860,0:03:52.716 They were so used to thinking about it 0:03:52.740,0:03:55.516 from the framework[br]of being a tuberculosis drug 0:03:55.540,0:03:57.596 that they actually just listed it 0:03:57.620,0:04:00.396 as a side effect, an adverse side effect. 0:04:00.420,0:04:01.571 As you can see here, 0:04:01.596,0:04:05.620 a lot of these patients in 1954[br]are experiencing severe euphoria. 0:04:06.900,0:04:10.516 And they were worried[br]that this might somehow interfere 0:04:10.540,0:04:13.396 with their recovering from tuberculosis. 0:04:13.420,0:04:19.676 So they recommended that iproniazid[br]only be used in cases of extreme TB 0:04:19.700,0:04:23.380 and in patients that were[br]highly emotionally stable, 0:04:24.220,0:04:28.116 which is of course the exact opposite[br]of how we use it as an antidepressant. 0:04:28.140,0:04:32.596 They were so used to looking at it[br]from the perspective of this one disease, 0:04:32.620,0:04:36.540 they could not see the larger implications[br]for another disease. 0:04:37.380,0:04:40.076 And to be fair,[br]it's not entirely their fault. 0:04:40.100,0:04:42.876 Functional fixedness[br]is a bias that affects all of us. 0:04:42.900,0:04:46.356 It's a tendency to only[br]be able to think of an object 0:04:46.380,0:04:48.980 in terms of its traditional[br]use or function. 0:04:49.740,0:04:51.636 And mental set is another thing. Right? 0:04:51.660,0:04:53.676 That's sort of this preconceived framework 0:04:53.700,0:04:55.476 with which we approach problems. 0:04:55.500,0:04:58.756 And that actually makes repurposing[br]pretty hard for all of us, 0:04:58.780,0:05:02.316 which is, I guess, why they gave[br]a TV show to the guy who was, 0:05:02.340,0:05:04.140 like, really great at repurposing. 0:05:04.660,0:05:06.540 (Laughter) 0:05:07.180,0:05:11.516 So the effects in both the case[br]of iproniazid and imipramine, 0:05:11.540,0:05:12.916 they were so strong -- 0:05:12.940,0:05:15.156 there was mania,[br]or people dancing in the halls. 0:05:15.180,0:05:18.316 It's actually not that surprising[br]they were caught. 0:05:18.340,0:05:21.820 But it does make you wonder[br]what else we've missed. 0:05:23.020,0:05:25.196 So iproniazid and imipramine, 0:05:25.220,0:05:27.636 they're more than just[br]a case study in repurposing. 0:05:27.660,0:05:30.636 They have two other things in common[br]that are really important. 0:05:30.660,0:05:33.156 One, they have terrible side effects. 0:05:33.180,0:05:35.796 That includes liver toxicity, 0:05:35.820,0:05:38.796 weight gain of over 50 pounds, 0:05:38.820,0:05:40.596 suicidality. 0:05:40.620,0:05:44.796 And two, they both[br]increase levels of serotonin, 0:05:44.820,0:05:47.156 which is a chemical signal in the brain, 0:05:47.180,0:05:48.380 or a neurotransmitter. 0:05:49.380,0:05:51.876 And those two things together,[br]right, one or the two, 0:05:51.900,0:05:53.516 may not have been that important, 0:05:53.540,0:05:57.276 but the two together meant[br]that we had to develop safer drugs, 0:05:57.300,0:06:00.820 and that serotonin seemed[br]like a pretty good place to start. 0:06:01.660,0:06:05.556 So we developed drugs[br]to more specifically focus on serotonin, 0:06:05.580,0:06:09.236 the selective serotonin[br]reuptake inhibitors, so the SSRIs, 0:06:09.260,0:06:11.996 the most famous of which is Prozac. 0:06:12.020,0:06:13.996 And that was 30 years ago, 0:06:14.020,0:06:17.220 and since then we have mostly[br]just worked on optimizing those drugs. 0:06:17.740,0:06:20.956 And the SSRIs, they are better[br]than the drugs that came before them, 0:06:20.980,0:06:23.076 but they still have a lot of side effects, 0:06:23.100,0:06:25.996 including weight gain, insomnia, 0:06:26.020,0:06:27.220 suicidality -- 0:06:28.100,0:06:30.436 and they take a really long time to work, 0:06:30.460,0:06:32.996 something like four to six weeks[br]in a lot of patients. 0:06:33.020,0:06:35.196 And that's in the patients[br]where they do work. 0:06:35.220,0:06:38.076 There are a lot of patients[br]where these drugs don't work. 0:06:38.100,0:06:41.476 And that means now, in 2016, 0:06:41.500,0:06:45.316 we still have no cures[br]for any mood disorders, 0:06:45.340,0:06:47.396 just drugs that suppress symptoms, 0:06:47.420,0:06:51.476 which is kind of the difference between[br]taking a painkiller for an infection 0:06:51.500,0:06:52.916 versus an antibiotic. 0:06:52.940,0:06:54.796 A painkiller will make you feel better, 0:06:54.820,0:06:57.900 but is not going to do anything[br]to treat that underlying disease. 0:06:58.700,0:07:01.036 And it was this flexibility[br]in our thinking 0:07:01.060,0:07:03.996 that let us recognize[br]that iproniazid and imipramine 0:07:04.020,0:07:06.116 could be repurposed in this way, 0:07:06.140,0:07:08.116 which led us to the serotonin hypothesis, 0:07:08.140,0:07:11.140 which we then, ironically, fixated on. 0:07:11.980,0:07:14.516 This is brain signaling, serotonin, 0:07:14.540,0:07:15.796 from an SSRI commercial. 0:07:15.820,0:07:18.180 In case you're not clear,[br]this is a dramatization. 0:07:18.660,0:07:22.716 And in science, we try[br]and remove our bias, right, 0:07:22.740,0:07:25.116 by running double-blinded experiments 0:07:25.140,0:07:28.836 or being statistically agnostic[br]as to what our results will be. 0:07:28.860,0:07:33.156 But bias creeps in more insidiously[br]in what we choose to study 0:07:33.180,0:07:34.900 and how we choose to study it. 0:07:36.260,0:07:39.836 So we've focused on serotonin now[br]for the past 30 years, 0:07:39.860,0:07:42.100 often to the exclusion of other things. 0:07:42.860,0:07:44.220 We still have no cures, 0:07:45.180,0:07:48.596 and what if serotonin[br]isn't all there is to depression? 0:07:48.620,0:07:50.676 What if it's not even the key part of it? 0:07:50.700,0:07:52.876 That means no matter how much time 0:07:52.900,0:07:55.636 or money or effort we put into it, 0:07:55.660,0:07:57.580 it will never lead to a cure. 0:07:58.500,0:08:01.076 In the past few years,[br]doctors have discovered 0:08:01.100,0:08:06.020 probably what is the first truly new[br]antidepressant since the SSRIs, 0:08:06.540,0:08:07.836 Calypsol, 0:08:07.860,0:08:11.316 and this drug works very quickly,[br]within a few hours or a day, 0:08:11.340,0:08:13.236 and it doesn't work on serotonin. 0:08:13.260,0:08:15.940 It works on glutamate,[br]which is another neurotransmitter. 0:08:16.380,0:08:17.876 And it's also repurposed. 0:08:17.900,0:08:20.980 It was traditionally used[br]as anesthesia in surgery. 0:08:21.540,0:08:23.196 But unlike those other drugs, 0:08:23.220,0:08:25.036 which were recognized pretty quickly, 0:08:25.060,0:08:26.756 it took us 20 years 0:08:26.780,0:08:29.436 to realize that Calypsol[br]was an antidepressant, 0:08:29.460,0:08:32.316 despite the fact that it's actually[br]a better antidepressant, 0:08:32.340,0:08:33.956 probably, than those other drugs. 0:08:33.980,0:08:38.076 It's actually probably because of the fact[br]that it's a better antidepressant 0:08:38.100,0:08:39.995 that it was harder for us to recognize. 0:08:40.019,0:08:42.100 There was no mania to signal its effects. 0:08:42.580,0:08:45.676 So in 2013, up at Columbia University, 0:08:45.700,0:08:47.276 I was working with my colleague, 0:08:47.300,0:08:49.276 Dr. Christine Ann Denny, 0:08:49.300,0:08:53.100 and we were studying Calypsol[br]as an antidepressant in mice. 0:08:53.660,0:08:56.476 And Calypsol has, like,[br]a really short half-life, 0:08:56.500,0:08:59.556 which means it's out of your body[br]within a few hours. 0:08:59.580,0:09:00.996 And we were just piloting. 0:09:01.020,0:09:03.276 So we would give an injection to mice, 0:09:03.300,0:09:04.596 and then we'd wait a week, 0:09:04.620,0:09:07.300 and then we'd run[br]another experiment to save money. 0:09:08.020,0:09:10.156 And one of the experiments I was running, 0:09:10.180,0:09:11.836 we would stress the mice, 0:09:11.860,0:09:14.076 and we used that as a model of depression. 0:09:14.100,0:09:17.436 And at first it kind of just looked[br]like it didn't really work at all. 0:09:17.460,0:09:18.980 So we could have stopped there. 0:09:19.540,0:09:22.436 But I have run this model[br]of depression for years, 0:09:22.460,0:09:24.356 and the data just looked kind of weird. 0:09:24.380,0:09:26.236 It didn't really look right to me. 0:09:26.260,0:09:27.476 So I went back, 0:09:27.500,0:09:28.996 and we reanalyzed it 0:09:29.020,0:09:32.836 based on whether or not they had gotten[br]that one injection of Calypsol 0:09:32.860,0:09:34.060 a week beforehand. 0:09:34.940,0:09:36.956 And it looked kind of like this. 0:09:36.980,0:09:39.116 So if you look at the far left, 0:09:39.140,0:09:41.636 if you put a mouse in a new space, 0:09:41.660,0:09:43.916 this is the box, it's very exciting, 0:09:43.940,0:09:46.076 a mouse will walk around and explore, 0:09:46.100,0:09:50.396 and you can see that pink line[br]is actually the measure of them walking. 0:09:50.420,0:09:53.596 And we also give it[br]another mouse in a pencil cup 0:09:53.620,0:09:55.676 that it can decide to interact with. 0:09:55.700,0:09:58.916 This is also a dramatization,[br]in case that's not clear. 0:09:58.940,0:10:02.636 And a normal mouse will explore. 0:10:02.660,0:10:03.900 It will be social. 0:10:04.620,0:10:05.996 Check out what's going on. 0:10:06.020,0:10:08.916 If you stress a mouse[br]in this depression model, 0:10:08.940,0:10:10.220 which is the middle box, 0:10:11.100,0:10:12.996 they aren't social, they don't explore. 0:10:13.020,0:10:16.300 They mostly just kind of hide[br]in that back corner, behind a cup. 0:10:17.020,0:10:20.116 Yet the mice that had gotten[br]that one injection of Calypsol, 0:10:20.140,0:10:21.340 here on your right, 0:10:22.060,0:10:24.020 they were exploring, they were social. 0:10:24.740,0:10:27.220 They looked like they[br]had never been stressed at all, 0:10:28.020,0:10:29.220 which is impossible. 0:10:30.260,0:10:31.980 So we could have just stopped there, 0:10:32.780,0:10:37.076 but Christine had also used[br]Calypsol before as anesthesia, 0:10:37.100,0:10:38.676 and a few years ago she had seen 0:10:38.700,0:10:41.076 that it seemed to have[br]some weird effects on cells 0:10:41.100,0:10:42.316 and some other behavior 0:10:42.340,0:10:45.356 that also seemed to last[br]long after the drug, 0:10:45.380,0:10:46.636 maybe a few weeks. 0:10:46.660,0:10:47.916 So we were like, OK, 0:10:47.940,0:10:50.116 maybe this is not completely impossible, 0:10:50.140,0:10:51.636 but we were really skeptical. 0:10:51.660,0:10:54.196 So we did what you do in science[br]when you're not sure, 0:10:54.220,0:10:55.420 and we ran it again. 0:10:56.460,0:10:59.476 And I remember being in the animal room, 0:10:59.500,0:11:03.156 moving mice from box to box[br]to test them, 0:11:03.180,0:11:06.796 and Christine was actually sitting[br]on the floor with the computer in her lap 0:11:06.820,0:11:08.236 so the mice couldn't see her, 0:11:08.260,0:11:10.516 and she was analyzing[br]the data in real time. 0:11:10.540,0:11:11.916 And I remember us yelling, 0:11:11.940,0:11:15.236 which you're not supposed to do[br]in an animal room where you're testing, 0:11:15.260,0:11:16.836 because it had worked. 0:11:16.860,0:11:21.236 It seemed like these mice[br]were protected against stress, 0:11:21.260,0:11:24.316 or they were inappropriately happy,[br]however you want to call it. 0:11:24.340,0:11:26.780 And we were really excited. 0:11:27.820,0:11:31.300 And then we were really skeptical,[br]because it was too good to be true. 0:11:31.860,0:11:33.060 So we ran it again. 0:11:33.740,0:11:36.476 And then we ran it again in a PTSD model, 0:11:36.500,0:11:38.916 and we ran it again[br]in a physiological model, 0:11:38.940,0:11:41.156 where all we did was give stress hormones. 0:11:41.180,0:11:42.796 And we had our undergrads run it. 0:11:42.820,0:11:46.940 And then we had our collaborators[br]halfway across the world in France run it. 0:11:47.780,0:11:50.996 And every time someone ran it,[br]they confirmed the same thing. 0:11:51.020,0:11:53.836 It seemed like[br]this one injection of Calypsol 0:11:53.860,0:11:56.620 was somehow protecting[br]against stress for weeks. 0:11:57.180,0:11:59.036 And we only published this a year ago, 0:11:59.060,0:12:03.140 but since then other labs[br]have independently confirmed this effect. 0:12:03.940,0:12:05.860 So we don't know what causes depression, 0:12:06.460,0:12:10.156 but we do know that stress[br]is the initial trigger 0:12:10.180,0:12:12.516 in 80 percent of cases, 0:12:12.540,0:12:14.756 and depression and PTSD[br]are different diseases, 0:12:14.780,0:12:16.796 but this is something[br]they share in common. 0:12:16.820,0:12:18.636 Right? It is traumatic stress 0:12:18.660,0:12:21.556 like active combat or natural disasters 0:12:21.580,0:12:24.036 or community violence or sexual assault 0:12:24.060,0:12:26.340 that causes post-traumatic[br]stress disorder, 0:12:26.980,0:12:32.596 and not everyone that is exposed to stress[br]develops a mood disorder. 0:12:32.620,0:12:35.516 And this ability to experience[br]stress and be resilient 0:12:35.540,0:12:39.700 and bounce back and not develop[br]depression or PTSD 0:12:40.500,0:12:42.756 is known as stress resilience, 0:12:42.780,0:12:44.636 and it varies between people. 0:12:44.660,0:12:47.996 And we have always thought of it[br]as just sort of this passive property. 0:12:48.020,0:12:50.556 It's the absence of susceptibility factors 0:12:50.580,0:12:52.660 and risk factors for these disorders. 0:12:53.620,0:12:55.500 But what if it were active? 0:12:56.420,0:12:57.916 Maybe we could enhance it, 0:12:57.940,0:13:00.100 sort of akin to putting on armor. 0:13:01.220,0:13:05.820 We had accidentally discovered[br]the first resilience-enhancing drug. 0:13:06.740,0:13:09.516 And like I said, we only gave[br]a tiny amount of the drug, 0:13:09.540,0:13:11.116 and it lasted for weeks, 0:13:11.140,0:13:14.356 and that's not like anything[br]you see with antidepressants. 0:13:14.380,0:13:18.700 But it is actually kind of similar[br]to what you see in immune vaccines. 0:13:19.180,0:13:22.116 So in immune vaccines,[br]you'll get your shots, 0:13:22.140,0:13:25.516 and then weeks, months, years later, 0:13:25.540,0:13:27.876 when you're actually exposed to bacteria, 0:13:27.900,0:13:30.356 it's not the vaccine in your body[br]that protects you. 0:13:30.380,0:13:31.756 It's your own immune system 0:13:31.780,0:13:35.916 that's developed resistance and resilience[br]to this bacteria that fights it off, 0:13:35.940,0:13:38.076 and you actually never get the infection, 0:13:38.100,0:13:41.156 which is very different[br]from, say, our treatments. Right? 0:13:41.180,0:13:44.996 In that case, you get the infection,[br]you're exposed to the bacteria, 0:13:45.020,0:13:48.876 you're sick, and then you take,[br]say, an antibiotic which cures it, 0:13:48.900,0:13:52.140 and those drugs are actually working[br]to kill the bacteria. 0:13:52.780,0:13:55.276 Or similar to as I said before,[br]with this palliative, 0:13:55.300,0:13:58.156 you'll take something[br]that will suppress the symptoms, 0:13:58.180,0:14:00.876 but it won't treat[br]the underlying infection, 0:14:00.900,0:14:04.236 and you'll only feel better[br]during the time in which you're taking it, 0:14:04.260,0:14:06.196 which is why you have to keep taking it. 0:14:06.220,0:14:08.916 And in depression and PTSD -- 0:14:08.940,0:14:10.916 here we have your stress exposure -- 0:14:10.940,0:14:13.556 we only have palliative care. 0:14:13.580,0:14:16.076 Antidepressants only suppress symptoms, 0:14:16.100,0:14:18.956 and that is why you basically[br]have to keep taking them 0:14:18.980,0:14:20.676 for the life of the disease, 0:14:20.700,0:14:22.900 which is often[br]the length of your own life. 0:14:23.940,0:14:28.156 So we're calling our resilience-enhancing[br]drugs "paravaccines," 0:14:28.180,0:14:29.716 which means vaccine-like, 0:14:29.740,0:14:32.236 because it seems[br]like they might have the potential 0:14:32.260,0:14:34.076 to protect against stress 0:14:34.100,0:14:37.516 and prevent mice from developing 0:14:37.540,0:14:40.300 depression and post-traumatic[br]stress disorder. 0:14:40.780,0:14:44.220 Also, not all antidepressants[br]are also paravaccines. 0:14:45.300,0:14:46.916 We tried Prozac as well, 0:14:46.940,0:14:48.300 and that had no effect. 0:14:49.060,0:14:52.076 So if this were to translate into humans, 0:14:52.100,0:14:54.676 we might be able to protect people 0:14:54.700,0:14:56.956 who are predictably at risk 0:14:56.980,0:15:00.836 against stress-induced disorders[br]like depression and PTSD. 0:15:00.860,0:15:03.996 So that's first responders[br]and firefighters, 0:15:04.020,0:15:08.156 refugees, prisoners and prison guards, 0:15:08.180,0:15:10.260 soldiers, you name it. 0:15:11.220,0:15:15.020 And to give you a sense[br]of the scale of these diseases, 0:15:15.620,0:15:18.676 in 2010, the global burden of disease 0:15:18.700,0:15:22.540 was estimated at 2.5 trillion dollars, 0:15:23.060,0:15:24.596 and since they are chronic, 0:15:24.620,0:15:27.836 that cost is compounding[br]and is therefore expected to rise 0:15:27.860,0:15:31.100 up to six trillion dollars[br]in just the next 15 years. 0:15:32.460,0:15:34.039 As I mentioned before, 0:15:34.064,0:15:38.140 repurposing can be challenging[br]because of our prior biases. 0:15:38.860,0:15:40.380 Calypsol has another name, 0:15:41.100,0:15:42.300 ketamine, 0:15:43.380,0:15:44.940 which also goes by another name, 0:15:45.460,0:15:46.876 Special K, 0:15:46.900,0:15:49.300 which is a club drug and drug of abuse. 0:15:50.540,0:15:53.636 It's still used across the world[br]as an anesthetic. 0:15:53.660,0:15:56.516 It's used in children.[br]We use it on the battlefield. 0:15:56.540,0:15:59.516 It's actually the drug of choice[br]in a lot of developing nations, 0:15:59.540,0:16:01.396 because it doesn't affect breathing. 0:16:01.420,0:16:06.100 It is on the World Health Organization[br]list of most essential medicines. 0:16:06.580,0:16:10.140 If we had discovered ketamine[br]as a paravaccine first, 0:16:10.820,0:16:13.676 it'd be pretty easy for us to develop it, 0:16:13.700,0:16:17.556 but as is, we have to compete[br]with our functional fixedness 0:16:17.580,0:16:20.380 and mental set that kind of interfere. 0:16:21.700,0:16:25.556 Fortunately, it's not[br]the only compound we have discovered 0:16:25.580,0:16:29.020 that has these prophylactic,[br]paravaccine qualities, 0:16:29.700,0:16:31.900 but all of the other drugs[br]we've discovered, 0:16:32.780,0:16:34.956 or compounds if you will,[br]they're totally new, 0:16:34.980,0:16:38.596 they have to go through[br]the entire FDA approval process -- 0:16:38.620,0:16:42.196 if they make it before[br]they can ever be used in humans. 0:16:42.220,0:16:43.876 And that will be years. 0:16:43.900,0:16:46.156 So if we wanted something sooner, 0:16:46.180,0:16:48.556 ketamine is already FDA-approved. 0:16:48.580,0:16:51.276 It's generic, it's available. 0:16:51.300,0:16:55.460 We could develop it for a fraction[br]of the price and a fraction of the time. 0:16:56.380,0:17:00.756 But actually, beyond[br]functional fixedness and mental set, 0:17:00.780,0:17:04.356 there's a real other challenge[br]to repurposing drugs, 0:17:04.380,0:17:05.579 which is policy. 0:17:06.179,0:17:08.395 There are no incentives in place 0:17:08.419,0:17:12.155 once a drug is generic and off patent[br]and no longer exclusive 0:17:12.179,0:17:14.516 to encourage pharma companies[br]to develop them, 0:17:14.540,0:17:15.969 because they don't make money. 0:17:16.380,0:17:19.500 And that's not true for just ketamine.[br]That is true for all drugs. 0:17:20.579,0:17:26.236 Regardless, the idea itself[br]is completely novel in psychiatry, 0:17:26.260,0:17:30.156 to use drugs to prevent mental illness 0:17:30.180,0:17:31.540 as opposed to just treat it. 0:17:32.740,0:17:37.796 It is possible that 20, 50,[br]100 years from now, 0:17:37.820,0:17:41.916 we will look back now[br]at depression and PTSD 0:17:41.940,0:17:45.156 the way we look back[br]at tuberculosis sanitoriums 0:17:45.180,0:17:46.380 as a thing of the past. 0:17:47.180,0:17:52.420 This could be the beginning of the end[br]of the mental health epidemic. 0:17:53.380,0:17:56.580 But as a great scientist once said, 0:17:57.900,0:18:00.156 "Only a fool is sure of anything. 0:18:00.180,0:18:02.220 A wise man keeps on guessing." 0:18:04.044,0:18:05.284 Thank you, guys. 0:18:05.780,0:18:09.846 (Applause)