1 00:00:00,630 --> 00:00:03,858 So raise your hand if you know someone 2 00:00:03,858 --> 00:00:06,505 in your immediate family or circle of friends 3 00:00:06,505 --> 00:00:09,993 who suffers from some form of mental illness. 4 00:00:09,993 --> 00:00:12,777 Yeah. I thought so. Not surprised. 5 00:00:12,777 --> 00:00:15,072 And raise your hand if you think that 6 00:00:15,072 --> 00:00:17,897 basic research on fruit flies has anything to do 7 00:00:17,897 --> 00:00:22,359 with understanding mental illness in humans. 8 00:00:22,359 --> 00:00:25,152 Yeah. I thought so. I'm also not surprised. 9 00:00:25,152 --> 00:00:28,472 I can see I've got my work cut out for me here. 10 00:00:28,472 --> 00:00:31,060 As we heard from Dr. Insel this morning, 11 00:00:31,060 --> 00:00:35,273 psychiatric disorders like autism, depression and schizophrenia 12 00:00:35,273 --> 00:00:38,148 take a terrible toll on human suffering. 13 00:00:38,148 --> 00:00:41,361 We know much less about their treatment 14 00:00:41,361 --> 00:00:43,967 and the understanding of their basic mechanisms 15 00:00:43,967 --> 00:00:46,586 than we do about diseases of the body. 16 00:00:46,586 --> 00:00:49,229 Think about it: In 2013, 17 00:00:49,229 --> 00:00:51,184 the second decade of the millennium, 18 00:00:51,184 --> 00:00:53,549 if you're concerned about a cancer diagnosis 19 00:00:53,549 --> 00:00:56,068 and you go to your doctor, you get bone scans, 20 00:00:56,068 --> 00:00:58,996 biopsies and blood tests. 21 00:00:58,996 --> 00:01:02,861 In 2013, if you're concerned about a depression diagnosis, 22 00:01:02,861 --> 00:01:04,824 you go to your doctor, and what do you get? 23 00:01:04,824 --> 00:01:06,811 A questionnaire. 24 00:01:06,811 --> 00:01:09,240 Now, part of the reason for this is that we have 25 00:01:09,240 --> 00:01:13,063 an oversimplified and increasingly outmoded view 26 00:01:13,063 --> 00:01:16,950 of the biological basis of psychiatric disorders. 27 00:01:16,950 --> 00:01:18,193 We tend to view them -- 28 00:01:18,193 --> 00:01:21,038 and the popular press aids and abets this view -- 29 00:01:21,038 --> 00:01:24,054 as chemical imbalances in the brain, 30 00:01:24,054 --> 00:01:27,738 as if the brain were some kind of bag of chemical soup 31 00:01:27,738 --> 00:01:31,938 full of dopamine, serotonin and norepinephrine. 32 00:01:31,938 --> 00:01:34,265 This view is conditioned by the fact 33 00:01:34,265 --> 00:01:37,671 that many of the drugs that are prescribed to treat these disorders, 34 00:01:37,671 --> 00:01:42,342 like Prozac, act by globally changing brain chemistry, 35 00:01:42,342 --> 00:01:46,318 as if the brain were indeed a bag of chemical soup. 36 00:01:46,318 --> 00:01:48,219 But that can't be the answer, 37 00:01:48,219 --> 00:01:51,456 because these drugs actually don't work all that well. 38 00:01:51,456 --> 00:01:54,632 A lot of people won't take them, or stop taking them, 39 00:01:54,632 --> 00:01:57,289 because of their unpleasant side effects. 40 00:01:57,289 --> 00:01:59,349 These drugs have so many side effects 41 00:01:59,349 --> 00:02:03,305 because using them to treat a complex psychiatric disorder 42 00:02:03,305 --> 00:02:05,994 is a bit like trying to change your engine oil 43 00:02:05,994 --> 00:02:10,107 by opening a can and pouring it all over the engine block. 44 00:02:10,107 --> 00:02:12,257 Some of it will dribble into the right place, 45 00:02:12,257 --> 00:02:15,358 but a lot of it will do more harm than good. 46 00:02:15,358 --> 00:02:17,596 Now, an emerging view 47 00:02:17,596 --> 00:02:20,546 that you also heard about from Dr. Insel this morning, 48 00:02:20,546 --> 00:02:23,116 is that psychiatric disorders are actually 49 00:02:23,116 --> 00:02:26,590 disturbances of neural circuits that mediate 50 00:02:26,590 --> 00:02:30,109 emotion, mood and affect. 51 00:02:30,109 --> 00:02:31,871 When we think about cognition, 52 00:02:31,871 --> 00:02:35,447 we analogize the brain to a computer. That's no problem. 53 00:02:35,447 --> 00:02:38,028 Well it turns out that the computer analogy 54 00:02:38,028 --> 00:02:40,411 is just as valid for emotion. 55 00:02:40,411 --> 00:02:43,197 It's just that we don't tend to think about it that way. 56 00:02:43,197 --> 00:02:46,480 But we know much less about the circuit basis 57 00:02:46,480 --> 00:02:48,379 of psychiatric disorders 58 00:02:48,379 --> 00:02:50,449 because of the overwhelming dominance 59 00:02:50,449 --> 00:02:53,801 of this chemical imbalance hypothesis. 60 00:02:53,801 --> 00:02:57,628 Now, it's not that chemicals are not important 61 00:02:57,628 --> 00:02:59,165 in psychiatric disorders. 62 00:02:59,165 --> 00:03:03,137 It's just that they don't bathe the brain like soup. 63 00:03:03,137 --> 00:03:06,786 Rather, they're released in very specific locations 64 00:03:06,786 --> 00:03:09,511 and they act on specific synapses 65 00:03:09,511 --> 00:03:13,199 to change the flow of information in the brain. 66 00:03:13,199 --> 00:03:15,636 So if we ever really want to understand 67 00:03:15,636 --> 00:03:18,341 the biological basis of psychiatric disorders, 68 00:03:18,341 --> 00:03:21,373 we need to pinpoint these locations in the brain 69 00:03:21,373 --> 00:03:23,107 where these chemicals act. 70 00:03:23,107 --> 00:03:26,586 Otherwise, we're going to keep pouring oil all over our mental engines 71 00:03:26,586 --> 00:03:29,543 and suffering the consequences. 72 00:03:29,543 --> 00:03:32,602 Now to begin to overcome our ignorance 73 00:03:32,602 --> 00:03:36,136 of the role of brain chemistry in brain circuitry, 74 00:03:36,136 --> 00:03:38,816 it's helpful to work on what we biologists call 75 00:03:38,816 --> 00:03:40,395 "model organisms," 76 00:03:40,395 --> 00:03:43,729 animals like fruit flies and laboratory mice, 77 00:03:43,729 --> 00:03:47,154 in which we can apply powerful genetic techniques 78 00:03:47,154 --> 00:03:50,779 to molecularly identify and pinpoint 79 00:03:50,779 --> 00:03:52,342 specific classes of neurons, 80 00:03:52,342 --> 00:03:55,245 as you heard about in Allan Jones's talk this morning. 81 00:03:55,245 --> 00:03:57,706 Moreover, once we can do that, 82 00:03:57,706 --> 00:04:00,455 we can actually activate specific neurons 83 00:04:00,455 --> 00:04:04,666 or we can destroy or inhibit the activity of those neurons. 84 00:04:04,666 --> 00:04:07,380 So if we inhibit a particular type of neuron, 85 00:04:07,380 --> 00:04:09,845 and we find that a behavior is blocked, 86 00:04:09,845 --> 00:04:12,059 we can conclude that those neurons 87 00:04:12,059 --> 00:04:15,023 are necessary for that behavior. 88 00:04:15,023 --> 00:04:17,405 On the other hand, if we activate a group of neurons 89 00:04:17,405 --> 00:04:20,219 and we find that that produces the behavior, 90 00:04:20,219 --> 00:04:24,293 we can conclude that those neurons are sufficient for the behavior. 91 00:04:24,293 --> 00:04:27,302 So in this way, by doing this kind of test, 92 00:04:27,302 --> 00:04:30,825 we can draw cause and effect relationships 93 00:04:30,825 --> 00:04:33,181 between the activity of specific neurons 94 00:04:33,181 --> 00:04:36,094 in particular circuits and particular behaviors, 95 00:04:36,094 --> 00:04:38,531 something that is extremely difficult, if not impossible, 96 00:04:38,531 --> 00:04:43,582 to do right now in humans. 97 00:04:43,582 --> 00:04:46,419 But can an organism like a fruit fly, which is -- 98 00:04:46,419 --> 00:04:48,619 it's a great model organism 99 00:04:48,619 --> 00:04:51,157 because it's got a small brain, 100 00:04:51,157 --> 00:04:54,944 it's capable of complex and sophisticated behaviors, 101 00:04:54,944 --> 00:04:58,094 it breeds quickly, and it's cheap. 102 00:04:58,094 --> 00:04:59,889 But can an organism like this 103 00:04:59,889 --> 00:05:03,732 teach us anything about emotion-like states? 104 00:05:03,732 --> 00:05:07,032 Do these organisms even have emotion-like states, 105 00:05:07,032 --> 00:05:10,395 or are they just little digital robots? 106 00:05:10,395 --> 00:05:13,595 Charles Darwin believed that insects have emotion 107 00:05:13,595 --> 00:05:16,145 and express them in their behaviors, as he wrote 108 00:05:16,145 --> 00:05:21,338 in his 1872 monograph on the expression of the emotions in man and animals. 109 00:05:21,338 --> 00:05:24,857 And my eponymous colleague, Seymour Benzer, believed it as well. 110 00:05:24,857 --> 00:05:28,271 Seymour is the man that introduced the use of drosophila 111 00:05:28,271 --> 00:05:31,794 here at CalTech in the '60s as a model organism 112 00:05:31,794 --> 00:05:35,391 to study the connection between genes and behavior. 113 00:05:35,391 --> 00:05:38,998 Seymour recruited me to CalTech in the late 1980s. 114 00:05:38,998 --> 00:05:43,432 He was my Jedi and my rabbi while he was here, 115 00:05:43,432 --> 00:05:45,820 and Seymour taught me both to love flies 116 00:05:45,820 --> 00:05:48,869 and also to play with science. 117 00:05:48,869 --> 00:05:51,985 So how do we ask this question? 118 00:05:51,985 --> 00:05:56,045 It's one thing to believe that flies have emotion-like states, 119 00:05:56,045 --> 00:05:59,208 but how do we actually find out whether that's true or not? 120 00:05:59,208 --> 00:06:03,158 Now, in humans we often infer emotional states, 121 00:06:03,158 --> 00:06:07,063 as you'll hear later today, from facial expressions. 122 00:06:07,063 --> 00:06:10,783 However, it's a little difficult to do that in fruit flies. 123 00:06:10,783 --> 00:06:14,096 (Laughter) 124 00:06:14,096 --> 00:06:17,233 It's kind of like landing on Mars 125 00:06:17,233 --> 00:06:19,938 and looking out the window of your spaceship 126 00:06:19,938 --> 00:06:22,408 at all the little green men who are surrounding it 127 00:06:22,408 --> 00:06:24,814 and trying to figure out, "How do I find out 128 00:06:24,814 --> 00:06:27,169 if they have emotions or not?" 129 00:06:27,169 --> 00:06:30,712 What can we do? It's not so easy. 130 00:06:30,712 --> 00:06:32,897 Well, one of the ways that we can start 131 00:06:32,897 --> 00:06:37,022 is to try to come up with some general characteristics 132 00:06:37,022 --> 00:06:40,770 or properties of emotion-like states 133 00:06:40,770 --> 00:06:44,234 such as arousal, and see if we can identify 134 00:06:44,234 --> 00:06:49,610 any fly behaviors that might exhibit some of those properties. 135 00:06:49,610 --> 00:06:52,430 So three important ones that I can think of 136 00:06:52,430 --> 00:06:57,102 are persistence, gradations in intensity, and valence. 137 00:06:57,102 --> 00:06:59,436 Persistence means long-lasting. 138 00:06:59,436 --> 00:07:03,397 We all know that the stimulus that triggers an emotion 139 00:07:03,397 --> 00:07:08,413 causes that emotion to last long after the stimulus is gone. 140 00:07:08,413 --> 00:07:11,503 Gradations of intensity means what it sounds like. 141 00:07:11,503 --> 00:07:16,086 You can dial up the intensity or dial down the intensity of an emotion. 142 00:07:16,086 --> 00:07:18,686 If you're a little bit unhappy, the corners of your mouth 143 00:07:18,686 --> 00:07:20,373 turn down and you sniffle, 144 00:07:20,373 --> 00:07:23,511 and if you're very unhappy, tears pour down your face 145 00:07:23,511 --> 00:07:25,343 and you might sob. 146 00:07:25,343 --> 00:07:29,722 Valence means good or bad, positive or negative. 147 00:07:29,722 --> 00:07:34,174 So we decided to see if flies could be provoked into showing 148 00:07:34,174 --> 00:07:36,625 the kind of behavior that you see 149 00:07:36,625 --> 00:07:39,435 by the proverbial wasp at the picnic table, 150 00:07:39,435 --> 00:07:42,120 you know, the one that keeps coming back to your hamburger 151 00:07:42,120 --> 00:07:44,649 the more vigorously you try to swat it away, 152 00:07:44,649 --> 00:07:46,933 and it seems to keep getting irritated. 153 00:07:46,933 --> 00:07:50,580 So we built a device, which we call a puff-o-mat, 154 00:07:50,580 --> 00:07:54,925 in which we could deliver little brief air puffs to fruit flies 155 00:07:54,925 --> 00:07:57,701 in these plastic tubes in our laboratory bench 156 00:07:57,701 --> 00:07:59,426 and blow them away. 157 00:07:59,426 --> 00:08:02,665 And what we found is that if we gave these flies 158 00:08:02,665 --> 00:08:05,513 in the puff-o-mat several puffs in a row, 159 00:08:05,513 --> 00:08:08,202 they became somewhat hyperactive 160 00:08:08,202 --> 00:08:12,637 and continued to run around for some time after the air puffs actually stopped 161 00:08:12,637 --> 00:08:15,501 and took a while to calm down. 162 00:08:15,501 --> 00:08:17,690 So we quantified this behavior 163 00:08:17,690 --> 00:08:20,702 using custom locomotor tracking software 164 00:08:20,702 --> 00:08:23,502 developed with my collaborator Pietro Perona, 165 00:08:23,502 --> 00:08:27,114 who's in the electrical engineering division here at CalTech. 166 00:08:27,114 --> 00:08:29,928 And what this quantification showed us is that, 167 00:08:29,928 --> 00:08:33,152 upon experiencing a train of these air puffs, 168 00:08:33,152 --> 00:08:37,466 the flies appear to enter a kind of state of hyperactivity 169 00:08:37,466 --> 00:08:40,064 which is persistent, long-lasting, 170 00:08:40,064 --> 00:08:42,568 and also appears to be graded. 171 00:08:42,568 --> 00:08:45,427 More puffs, or more intense puffs, 172 00:08:45,427 --> 00:08:49,340 make the state last for a longer period of time. 173 00:08:49,340 --> 00:08:51,376 So now we wanted to try to understand something 174 00:08:51,376 --> 00:08:55,090 about what controls the duration of this state. 175 00:08:55,090 --> 00:08:57,941 So we decided to use our puff-o-mat 176 00:08:57,941 --> 00:08:59,996 and our automated tracking software 177 00:08:59,996 --> 00:09:03,778 to screen through hundreds of lines of mutant fruit flies 178 00:09:03,778 --> 00:09:08,857 to see if we could find any that showed abnormal responses to the air puffs. 179 00:09:08,857 --> 00:09:11,204 And this is one of the great things about fruit flies. 180 00:09:11,204 --> 00:09:13,997 There are repositories where you can just pick up the phone 181 00:09:13,997 --> 00:09:17,638 and order hundreds of vials of flies of different mutants 182 00:09:17,638 --> 00:09:19,810 and screen them in your assay and then find out 183 00:09:19,810 --> 00:09:23,129 what gene is affected in the mutation. 184 00:09:23,129 --> 00:09:26,641 So doing the screen, we discovered one mutant 185 00:09:26,641 --> 00:09:30,115 that took much longer than normal to calm down 186 00:09:30,115 --> 00:09:32,392 after the air puffs, 187 00:09:32,392 --> 00:09:36,342 and when we examined the gene that was affected in this mutation, 188 00:09:36,342 --> 00:09:39,947 it turned out to encode a dopamine receptor. 189 00:09:39,947 --> 00:09:42,958 That's right -- flies, like people, have dopamine, 190 00:09:42,958 --> 00:09:45,730 and it acts on their brains and on their synapses 191 00:09:45,730 --> 00:09:48,280 through the same dopamine receptor molecules 192 00:09:48,280 --> 00:09:50,669 that you and I have. 193 00:09:50,669 --> 00:09:54,155 Dopamine plays a number of important functions in the brain, 194 00:09:54,155 --> 00:09:57,268 including in attention, arousal, reward, 195 00:09:57,268 --> 00:10:00,681 and disorders of the dopamine system have been linked 196 00:10:00,681 --> 00:10:03,781 to a number of mental disorders including drug abuse, 197 00:10:03,781 --> 00:10:08,015 Parkinson's disease, and ADHD. 198 00:10:08,015 --> 00:10:10,805 Now, in genetics, it's a little counterintuitive. 199 00:10:10,805 --> 00:10:14,065 We tend to infer the normal function of something 200 00:10:14,065 --> 00:10:17,775 by what doesn't happen when we take it away, 201 00:10:17,775 --> 00:10:20,778 by the opposite of what we see when we take it away. 202 00:10:20,778 --> 00:10:23,791 So when we take away the dopamine receptor 203 00:10:23,791 --> 00:10:26,348 and the flies take longer to calm down, 204 00:10:26,348 --> 00:10:30,194 from that we infer that the normal function of this receptor and dopamine 205 00:10:30,194 --> 00:10:34,679 is to cause the flies to calm down faster after the puff. 206 00:10:34,679 --> 00:10:37,629 And that's a bit reminiscent of ADHD, 207 00:10:37,629 --> 00:10:41,604 which has been linked to disorders of the dopamine system in humans. 208 00:10:41,604 --> 00:10:46,210 Indeed, if we increase the levels of dopamine in normal flies 209 00:10:46,210 --> 00:10:47,920 by feeding them cocaine 210 00:10:47,920 --> 00:10:50,892 after getting the appropriate DEA license 211 00:10:50,892 --> 00:10:54,892 — oh my God -- (Laughter) — 212 00:10:54,892 --> 00:10:58,064 we find indeed that these cocaine-fed flies 213 00:10:58,064 --> 00:11:01,106 calm down faster than normal flies do, 214 00:11:01,106 --> 00:11:04,305 and that's also reminiscent of ADHD, 215 00:11:04,305 --> 00:11:06,350 which is often treated with drugs like Ritalin 216 00:11:06,350 --> 00:11:09,369 that act similarly to cocaine. 217 00:11:09,369 --> 00:11:12,518 So slowly I began to realize that what started out 218 00:11:12,518 --> 00:11:16,167 as a rather playful attempt to try to annoy fruit flies 219 00:11:16,167 --> 00:11:20,143 might actually have some relevance to a human psychiatric disorder. 220 00:11:20,143 --> 00:11:22,369 Now, how far does this analogy go? 221 00:11:22,369 --> 00:11:25,491 As many of you know, individuals afflicted with ADHD 222 00:11:25,491 --> 00:11:27,828 also have learning disabilities. 223 00:11:27,828 --> 00:11:31,394 Is that true of our dopamine receptor mutant flies? 224 00:11:31,394 --> 00:11:34,114 Remarkably, the answer is yes. 225 00:11:34,114 --> 00:11:36,742 As Seymour showed back in the 1970s, 226 00:11:36,742 --> 00:11:39,193 flies, like songbirds, as you just heard, 227 00:11:39,193 --> 00:11:40,926 are capable of learning. 228 00:11:40,926 --> 00:11:45,369 You can train a fly to avoid an odor, shown here in blue, 229 00:11:45,369 --> 00:11:47,757 if you pair that odor with a shock. 230 00:11:47,757 --> 00:11:51,141 Then when you give those trained flies the chance to choose 231 00:11:51,141 --> 00:11:54,295 between a tube with the shock-paired odor and another odor, 232 00:11:54,295 --> 00:11:58,495 it avoids the tube containing the blue odor that was paired with shock. 233 00:11:58,495 --> 00:12:01,997 Well, if you do this test on dopamine receptor mutant flies, 234 00:12:01,997 --> 00:12:04,462 they don't learn. Their learning score is zero. 235 00:12:04,462 --> 00:12:08,273 They flunk out of CalTech. 236 00:12:08,273 --> 00:12:13,021 So that means that these flies have two abnormalities, 237 00:12:13,021 --> 00:12:16,071 or phenotypes, as we geneticists call them, 238 00:12:16,071 --> 00:12:21,583 that one finds in ADHD: hyperactivity and learning disability. 239 00:12:21,583 --> 00:12:25,946 Now what's the causal relationship, if anything, between these phenotypes? 240 00:12:25,946 --> 00:12:29,859 In ADHD, it's often assumed that the hyperactivity 241 00:12:29,859 --> 00:12:31,765 causes the learning disability. 242 00:12:31,765 --> 00:12:35,484 The kids can't sit still long enough to focus, so they don't learn. 243 00:12:35,484 --> 00:12:38,780 But it could equally be the case that it's the learning disabilities 244 00:12:38,780 --> 00:12:40,652 that cause the hyperactivity. 245 00:12:40,652 --> 00:12:45,122 Because the kids can't learn, they look for other things to distract their attention. 246 00:12:45,122 --> 00:12:48,179 And a final possibility is that there's no relationship at all 247 00:12:48,179 --> 00:12:50,583 between learning disabilities and hyperactivity, 248 00:12:50,583 --> 00:12:55,498 but that they are caused by a common underlying mechanism in ADHD. 249 00:12:55,498 --> 00:12:57,840 Now people have been wondering about this for a long time 250 00:12:57,840 --> 00:13:01,328 in humans, but in flies we can actually test this. 251 00:13:01,328 --> 00:13:04,412 And the way that we do this is to delve deeply into the mind 252 00:13:04,412 --> 00:13:08,678 of the fly and begin to untangle its circuitry using genetics. 253 00:13:08,678 --> 00:13:11,140 We take our dopamine receptor mutant flies 254 00:13:11,140 --> 00:13:15,704 and we genetically restore, or cure, the dopamine receptor 255 00:13:15,704 --> 00:13:18,939 by putting a good copy of the dopamine receptor gene 256 00:13:18,939 --> 00:13:20,990 back into the fly brain. 257 00:13:20,990 --> 00:13:24,825 But in each fly, we put it back only into certain neurons 258 00:13:24,825 --> 00:13:28,539 and not in others, and then we test each of these flies 259 00:13:28,539 --> 00:13:32,207 for their ability to learn and for hyperactivity. 260 00:13:32,207 --> 00:13:37,025 Remarkably, we find we can completely dissociate these two abnormalities. 261 00:13:37,025 --> 00:13:39,688 If we put a good copy of the dopamine receptor back 262 00:13:39,688 --> 00:13:42,649 in this elliptical structure called the central complex, 263 00:13:42,649 --> 00:13:46,726 the flies are no longer hyperactive, but they still can't learn. 264 00:13:46,726 --> 00:13:49,452 On the other hand, if we put the receptor back in a different structure 265 00:13:49,452 --> 00:13:50,970 called the mushroom body, 266 00:13:50,970 --> 00:13:54,055 the learning deficit is rescued, the flies learn well, 267 00:13:54,055 --> 00:13:55,885 but they're still hyperactive. 268 00:13:55,885 --> 00:13:58,135 What that tells us is that dopamine 269 00:13:58,135 --> 00:14:01,527 is not bathing the brain of these flies like soup. 270 00:14:01,527 --> 00:14:04,689 Rather, it's acting to control two different functions 271 00:14:04,689 --> 00:14:06,323 on two different circuits, 272 00:14:06,323 --> 00:14:10,227 so the reason there are two things wrong with our dopamine receptor flies 273 00:14:10,227 --> 00:14:14,402 is that the same receptor is controlling two different functions 274 00:14:14,402 --> 00:14:17,265 in two different regions of the brain. 275 00:14:17,265 --> 00:14:20,327 Whether the same thing is true in ADHD in humans 276 00:14:20,327 --> 00:14:22,703 we don't know, but these kinds of results 277 00:14:22,703 --> 00:14:26,180 should at least cause us to consider that possibility. 278 00:14:26,180 --> 00:14:30,153 So these results make me and my colleagues more convinced than ever 279 00:14:30,153 --> 00:14:33,565 that the brain is not a bag of chemical soup, 280 00:14:33,565 --> 00:14:37,092 and it's a mistake to try to treat complex psychiatric disorders 281 00:14:37,092 --> 00:14:39,803 just by changing the flavor of the soup. 282 00:14:39,803 --> 00:14:44,020 What we need to do is to use our ingenuity and our scientific knowledge 283 00:14:44,020 --> 00:14:46,728 to try to design a new generation of treatments 284 00:14:46,728 --> 00:14:51,016 that are targeted to specific neurons and specific regions of the brain 285 00:14:51,016 --> 00:14:54,354 that are affected in particular psychiatric disorders. 286 00:14:54,354 --> 00:14:57,554 If we can do that, we may be able to cure these disorders 287 00:14:57,554 --> 00:14:59,601 without the unpleasant side effects, 288 00:14:59,601 --> 00:15:02,347 putting the oil back in our mental engines, 289 00:15:02,347 --> 00:15:05,531 just where it's needed. Thank you very much.