0:00:00.530,0:00:03.491 So let's start with some good news, 0:00:03.491,0:00:05.840 and the good news has to do with what do we know 0:00:05.840,0:00:08.107 based on biomedical research 0:00:08.107,0:00:11.561 that actually has changed the outcomes 0:00:11.561,0:00:14.660 for many very serious diseases? 0:00:14.660,0:00:16.907 Let's start with leukemia, 0:00:16.907,0:00:19.435 acute lymphoblastic leukemia, ALL, 0:00:19.435,0:00:21.873 the most common cancer of children. 0:00:21.873,0:00:23.835 When I was a student, 0:00:23.835,0:00:27.675 the mortality rate was about 95 percent. 0:00:27.675,0:00:30.808 Today, some 25, 30 years later, we're talking about 0:00:30.808,0:00:34.435 a mortality rate that's reduced by 85 percent. 0:00:34.435,0:00:37.051 Six thousand children each year 0:00:37.051,0:00:41.240 who would have previously died of this disease are cured. 0:00:41.240,0:00:43.031 If you want the really big numbers, 0:00:43.031,0:00:45.859 look at these numbers for heart disease. 0:00:45.859,0:00:47.651 Heart disease used to be the biggest killer, 0:00:47.651,0:00:49.155 particularly for men in their 40s. 0:00:49.155,0:00:52.649 Today, we've seen a 63-percent reduction in mortality 0:00:52.649,0:00:54.710 from heart disease -- 0:00:54.710,0:00:59.595 remarkably, 1.1 million deaths averted every year. 0:00:59.595,0:01:02.316 AIDS, incredibly, has just been named, 0:01:02.316,0:01:04.597 in the past month, a chronic disease, 0:01:04.597,0:01:07.512 meaning that a 20-year-old who becomes infected with HIV 0:01:07.512,0:01:11.583 is expected not to live weeks, months, or a couple of years, 0:01:11.583,0:01:13.853 as we said only a decade ago, 0:01:13.853,0:01:16.245 but is thought to live decades, 0:01:16.245,0:01:20.741 probably to die in his '60s or '70s from other causes altogether. 0:01:20.741,0:01:23.766 These are just remarkable, remarkable changes 0:01:23.766,0:01:26.355 in the outlook for some of the biggest killers. 0:01:26.355,0:01:28.434 And one in particular 0:01:28.434,0:01:30.479 that you probably wouldn't know about, stroke, 0:01:30.479,0:01:32.080 which has been, along with heart disease, 0:01:32.080,0:01:34.258 one of the biggest killers in this country, 0:01:34.258,0:01:36.049 is a disease in which now we know 0:01:36.049,0:01:38.978 that if you can get people into the emergency room 0:01:38.978,0:01:41.152 within three hours of the onset, 0:01:41.152,0:01:43.757 some 30 percent of them will be able to leave the hospital 0:01:43.757,0:01:46.876 without any disability whatsoever. 0:01:46.876,0:01:49.133 Remarkable stories, 0:01:49.133,0:01:51.164 good-news stories, 0:01:51.164,0:01:54.229 all of which boil down to understanding 0:01:54.229,0:01:57.581 something about the diseases that has allowed us 0:01:57.581,0:02:00.904 to detect early and intervene early. 0:02:00.904,0:02:03.039 Early detection, early intervention, 0:02:03.039,0:02:06.109 that's the story for these successes. 0:02:06.109,0:02:08.845 Unfortunately, the news is not all good. 0:02:08.845,0:02:11.194 Let's talk about one other story 0:02:11.194,0:02:12.885 which has to do with suicide. 0:02:12.885,0:02:15.537 Now this is, of course, not a disease, per se. 0:02:15.537,0:02:18.625 It's a condition, or it's a situation 0:02:18.625,0:02:20.414 that leads to mortality. 0:02:20.414,0:02:23.494 What you may not realize is just how prevalent it is. 0:02:23.494,0:02:27.703 There are 38,000 suicides each year in the United States. 0:02:27.703,0:02:30.461 That means one about every 15 minutes. 0:02:30.461,0:02:33.237 Third most common cause of death amongst people 0:02:33.237,0:02:36.013 between the ages of 15 and 25. 0:02:36.013,0:02:38.261 It's kind of an extraordinary story when you realize 0:02:38.261,0:02:40.773 that this is twice as common as homicide 0:02:40.773,0:02:43.422 and actually more common as a source of death 0:02:43.422,0:02:46.757 than traffic fatalities in this country. 0:02:46.757,0:02:49.389 Now, when we talk about suicide, 0:02:49.389,0:02:52.501 there is also a medical contribution here, 0:02:52.501,0:02:54.933 because 90 percent of suicides 0:02:54.933,0:02:56.703 are related to a mental illness: 0:02:56.703,0:02:59.749 depression, bipolar disorder, schizophrenia, 0:02:59.749,0:03:02.807 anorexia, borderline personality. There's a long list 0:03:02.808,0:03:04.917 of disorders that contribute, 0:03:04.917,0:03:08.941 and as I mentioned before, often early in life. 0:03:08.941,0:03:12.145 But it's not just the mortality from these disorders. 0:03:12.145,0:03:13.787 It's also morbidity. 0:03:13.787,0:03:16.048 If you look at disability, 0:03:16.048,0:03:18.200 as measured by the World Health Organization 0:03:18.200,0:03:21.725 with something they call the Disability Adjusted Life Years, 0:03:21.725,0:03:23.821 it's kind of a metric that nobody would think of 0:03:23.821,0:03:25.135 except an economist, 0:03:25.135,0:03:28.577 except it's one way of trying to capture what is lost 0:03:28.577,0:03:31.760 in terms of disability from medical causes, 0:03:31.760,0:03:34.653 and as you can see, virtually 30 percent 0:03:34.653,0:03:36.917 of all disability from all medical causes 0:03:36.917,0:03:39.477 can be attributed to mental disorders, 0:03:39.477,0:03:41.861 neuropsychiatric syndromes. 0:03:41.861,0:03:44.013 You're probably thinking that doesn't make any sense. 0:03:44.013,0:03:46.685 I mean, cancer seems far more serious. 0:03:46.685,0:03:49.717 Heart disease seems far more serious. 0:03:49.717,0:03:52.757 But you can see actually they are further down this list, 0:03:52.757,0:03:55.037 and that's because we're talking here about disability. 0:03:55.037,0:03:57.829 What drives the disability for these disorders 0:03:57.829,0:04:01.733 like schizophrenia and bipolar and depression? 0:04:01.733,0:04:04.708 Why are they number one here? 0:04:04.708,0:04:06.217 Well, there are probably three reasons. 0:04:06.217,0:04:08.189 One is that they're highly prevalent. 0:04:08.189,0:04:11.484 About one in five people will suffer from one of these disorders 0:04:11.484,0:04:14.061 in the course of their lifetime. 0:04:14.061,0:04:16.381 A second, of course, is that, for some people, 0:04:16.381,0:04:17.965 these become truly disabling, 0:04:17.965,0:04:21.093 and it's about four to five percent, perhaps one in 20. 0:04:21.093,0:04:25.357 But what really drives these numbers, this high morbidity, 0:04:25.357,0:04:27.786 and to some extent the high mortality, 0:04:27.786,0:04:31.734 is the fact that these start very early in life. 0:04:31.734,0:04:34.829 Fifty percent will have onset by age 14, 0:04:34.829,0:04:37.949 75 percent by age 24, 0:04:37.949,0:04:41.414 a picture that is very different than what one would see 0:04:41.414,0:04:43.685 if you're talking about cancer or heart disease, 0:04:43.685,0:04:47.085 diabetes, hypertension -- most of the major illnesses 0:04:47.085,0:04:51.181 that we think about as being sources of morbidity and mortality. 0:04:51.181,0:04:57.491 These are, indeed, the chronic disorders of young people. 0:04:57.491,0:05:00.358 Now, I started by telling you that there were some good-news stories. 0:05:00.358,0:05:01.806 This is obviously not one of them. 0:05:01.806,0:05:04.685 This is the part of it that is perhaps most difficult, 0:05:04.685,0:05:07.269 and in a sense this is a kind of confession for me. 0:05:07.269,0:05:12.621 My job is to actually make sure that we make progress 0:05:12.621,0:05:14.973 on all of these disorders. 0:05:14.973,0:05:16.683 I work for the federal government. 0:05:16.683,0:05:18.701 Actually, I work for you. You pay my salary. 0:05:18.701,0:05:21.085 And maybe at this point, when you know what I do, 0:05:21.085,0:05:23.205 or maybe what I've failed to do, 0:05:23.205,0:05:25.414 you'll think that I probably ought to be fired, 0:05:25.414,0:05:27.569 and I could certainly understand that. 0:05:27.569,0:05:29.901 But what I want to suggest, and the reason I'm here 0:05:29.901,0:05:33.156 is to tell you that I think we're about to be 0:05:33.156,0:05:37.819 in a very different world as we think about these illnesses. 0:05:37.819,0:05:40.925 What I've been talking to you about so far is mental disorders, 0:05:40.925,0:05:42.641 diseases of the mind. 0:05:42.641,0:05:46.037 That's actually becoming a rather unpopular term these days, 0:05:46.037,0:05:48.237 and people feel that, for whatever reason, 0:05:48.237,0:05:51.614 it's politically better to use the term behavioral disorders 0:05:51.614,0:05:55.525 and to talk about these as disorders of behavior. 0:05:55.525,0:05:57.792 Fair enough. They are disorders of behavior, 0:05:57.792,0:05:59.792 and they are disorders of the mind. 0:05:59.792,0:06:02.197 But what I want to suggest to you 0:06:02.197,0:06:03.949 is that both of those terms, 0:06:03.949,0:06:06.967 which have been in play for a century or more, 0:06:06.967,0:06:09.787 are actually now impediments to progress, 0:06:09.787,0:06:14.117 that what we need conceptually to make progress here 0:06:14.117,0:06:19.325 is to rethink these disorders as brain disorders. 0:06:19.325,0:06:21.187 Now, for some of you, you're going to say, 0:06:21.187,0:06:23.406 "Oh my goodness, here we go again. 0:06:23.406,0:06:26.034 We're going to hear about a biochemical imbalance 0:06:26.034,0:06:27.769 or we're going to hear about drugs 0:06:27.769,0:06:32.595 or we're going to hear about some very simplistic notion 0:06:32.595,0:06:35.535 that will take our subjective experience 0:06:35.535,0:06:41.607 and turn it into molecules, or maybe into some sort of 0:06:41.607,0:06:44.825 very flat, unidimensional understanding 0:06:44.825,0:06:48.927 of what it is to have depression or schizophrenia. 0:06:48.927,0:06:53.425 When we talk about the brain, it is anything but 0:06:53.425,0:06:56.688 unidimensional or simplistic or reductionistic. 0:06:56.688,0:06:59.647 It depends, of course, on what scale 0:06:59.647,0:07:01.943 or what scope you want to think about, 0:07:01.943,0:07:08.223 but this is an organ of surreal complexity, 0:07:08.223,0:07:11.694 and we are just beginning to understand 0:07:11.694,0:07:13.867 how to even study it, whether you're thinking about 0:07:13.867,0:07:16.449 the 100 billion neurons that are in the cortex 0:07:16.449,0:07:18.594 or the 100 trillion synapses 0:07:18.594,0:07:20.953 that make up all the connections. 0:07:20.953,0:07:24.529 We have just begun to try to figure out 0:07:24.529,0:07:28.057 how do we take this very complex machine 0:07:28.057,0:07:30.801 that does extraordinary kinds of information processing 0:07:30.801,0:07:33.518 and use our own minds to understand 0:07:33.518,0:07:37.049 this very complex brain that supports our own minds. 0:07:37.049,0:07:39.609 It's actually a kind of cruel trick of evolution 0:07:39.609,0:07:43.439 that we simply don't have a brain 0:07:43.439,0:07:46.337 that seems to be wired well enough to understand itself. 0:07:46.337,0:07:48.651 In a sense, it actually makes you feel that 0:07:48.651,0:07:51.489 when you're in the safe zone of studying behavior or cognition, 0:07:51.489,0:07:52.812 something you can observe, 0:07:52.812,0:07:55.817 that in a way feels more simplistic and reductionistic 0:07:55.817,0:08:00.785 than trying to engage this very complex, mysterious organ 0:08:00.785,0:08:03.213 that we're beginning to try to understand. 0:08:03.213,0:08:06.869 Now, already in the case of the brain disorders 0:08:06.869,0:08:08.597 that I've been talking to you about, 0:08:08.597,0:08:10.870 depression, obsessive compulsive disorder, 0:08:10.870,0:08:13.032 post-traumatic stress disorder, 0:08:13.032,0:08:15.974 while we don't have an in-depth understanding 0:08:15.974,0:08:19.700 of how they are abnormally processed 0:08:19.700,0:08:21.805 or what the brain is doing in these illnesses, 0:08:21.805,0:08:24.860 we have been able to already identify 0:08:24.860,0:08:27.436 some of the connectional differences, or some of the ways 0:08:27.436,0:08:29.940 in which the circuitry is different 0:08:29.940,0:08:31.756 for people who have these disorders. 0:08:31.756,0:08:33.514 We call this the human connectome, 0:08:33.514,0:08:35.895 and you can think about the connectome 0:08:35.895,0:08:37.767 sort of as the wiring diagram of the brain. 0:08:37.767,0:08:39.871 You'll hear more about this in a few minutes. 0:08:39.871,0:08:42.822 The important piece here is that as you begin to look 0:08:42.822,0:08:46.799 at people who have these disorders, the one in five of us 0:08:46.799,0:08:48.627 who struggle in some way, 0:08:48.627,0:08:50.915 you find that there's a lot of variation 0:08:50.915,0:08:54.131 in the way that the brain is wired, 0:08:54.131,0:08:56.733 but there are some predictable patterns, and those patterns 0:08:56.733,0:09:00.547 are risk factors for developing one of these disorders. 0:09:00.547,0:09:03.539 It's a little different than the way we think about brain disorders 0:09:03.539,0:09:06.307 like Huntington's or Parkinson's or Alzheimer's disease 0:09:06.307,0:09:08.699 where you have a bombed-out part of your cortex. 0:09:08.699,0:09:11.959 Here we're talking about traffic jams, or sometimes detours, 0:09:11.959,0:09:14.706 or sometimes problems with just the way that things are connected 0:09:14.706,0:09:15.953 and the way that the brain functions. 0:09:15.953,0:09:19.123 You could, if you want, compare this to, 0:09:19.123,0:09:22.172 on the one hand, a myocardial infarction, a heart attack, 0:09:22.172,0:09:23.995 where you have dead tissue in the heart, 0:09:23.995,0:09:27.592 versus an arrhythmia, where the organ simply isn't functioning 0:09:27.592,0:09:29.843 because of the communication problems within it. 0:09:29.843,0:09:31.812 Either one would kill you; in only one of them 0:09:31.812,0:09:34.412 will you find a major lesion. 0:09:34.412,0:09:37.244 As we think about this, probably it's better to actually go 0:09:37.244,0:09:40.467 a little deeper into one particular disorder, and that would be schizophrenia, 0:09:40.467,0:09:42.603 because I think that's a good case 0:09:42.603,0:09:46.128 for helping to understand why thinking of this as a brain disorder matters. 0:09:46.128,0:09:50.006 These are scans from Judy Rapoport and her colleagues 0:09:50.006,0:09:52.178 at the National Institute of Mental Health 0:09:52.178,0:09:55.894 in which they studied children with very early onset schizophrenia, 0:09:55.894,0:09:57.364 and you can see already in the top 0:09:57.364,0:09:59.901 there's areas that are red or orange, yellow, 0:09:59.901,0:10:02.039 are places where there's less gray matter, 0:10:02.039,0:10:03.577 and as they followed them over five years, 0:10:03.577,0:10:05.815 comparing them to age match controls, 0:10:05.815,0:10:07.637 you can see that, particularly in areas like 0:10:07.637,0:10:09.953 the dorsolateral prefrontal cortex 0:10:09.953,0:10:14.283 or the superior temporal gyrus, there's a profound loss of gray matter. 0:10:14.283,0:10:15.826 And it's important, if you try to model this, 0:10:15.826,0:10:17.782 you can think about normal development 0:10:17.782,0:10:21.035 as a loss of cortical mass, loss of cortical gray matter, 0:10:21.035,0:10:24.699 and what's happening in schizophrenia is that you overshoot that mark, 0:10:24.699,0:10:26.268 and at some point, when you overshoot, 0:10:26.268,0:10:29.259 you cross a threshold, and it's that threshold 0:10:29.259,0:10:32.835 where we say, this is a person who has this disease, 0:10:32.835,0:10:35.123 because they have the behavioral symptoms 0:10:35.123,0:10:37.244 of hallucinations and delusions. 0:10:37.244,0:10:38.721 That's something we can observe. 0:10:38.721,0:10:44.363 But look at this closely and you can see that actually they've crossed a different threshold. 0:10:44.363,0:10:47.359 They've crossed a brain threshold much earlier, 0:10:47.359,0:10:50.499 that perhaps not at age 22 or 20, 0:10:50.499,0:10:53.267 but even by age 15 or 16 you can begin to see 0:10:53.267,0:10:55.627 the trajectory for development is quite different 0:10:55.627,0:10:59.142 at the level of the brain, not at the level of behavior. 0:10:59.142,0:11:01.237 Why does this matter? Well first because, 0:11:01.237,0:11:04.379 for brain disorders, behavior is the last thing to change. 0:11:04.379,0:11:07.289 We know that for Alzheimer's, for Parkinson's, for Huntington's. 0:11:07.289,0:11:09.723 There are changes in the brain a decade or more 0:11:09.723,0:11:14.763 before you see the first signs of a behavioral change. 0:11:14.763,0:11:17.707 The tools that we have now allow us to detect 0:11:17.707,0:11:22.004 these brain changes much earlier, long before the symptoms emerge. 0:11:22.004,0:11:25.403 But most important, go back to where we started. 0:11:25.403,0:11:28.619 The good-news stories in medicine 0:11:28.619,0:11:31.563 are early detection, early intervention. 0:11:31.563,0:11:35.227 If we waited until the heart attack, 0:11:35.227,0:11:39.202 we would be sacrificing 1.1 million lives 0:11:39.202,0:11:41.611 every year in this country to heart disease. 0:11:41.611,0:11:44.019 That is precisely what we do today 0:11:44.019,0:11:48.531 when we decide that everybody with one of these brain disorders, 0:11:48.531,0:11:51.733 brain circuit disorders, has a behavioral disorder. 0:11:51.733,0:11:54.957 We wait until the behavior becomes manifest. 0:11:54.957,0:11:59.516 That's not early detection. That's not early intervention. 0:11:59.516,0:12:01.321 Now to be clear, we're not quite ready to do this. 0:12:01.321,0:12:04.475 We don't have all the facts. We don't actually even know 0:12:04.475,0:12:07.024 what the tools will be, 0:12:07.024,0:12:11.283 nor what to precisely look for in every case to be able 0:12:11.283,0:12:15.488 to get there before the behavior emerges as different. 0:12:15.488,0:12:18.425 But this tells us how we need to think about it, 0:12:18.425,0:12:19.914 and where we need to go. 0:12:19.914,0:12:21.116 Are we going to be there soon? 0:12:21.116,0:12:23.794 I think that this is something that will happen 0:12:23.794,0:12:26.625 over the course of the next few years, but I'd like to finish 0:12:26.625,0:12:29.160 with a quote about trying to predict how this will happen 0:12:29.160,0:12:31.521 by somebody who's thought a lot about changes 0:12:31.521,0:12:33.849 in concepts and changes in technology. 0:12:33.849,0:12:36.113 "We always overestimate the change that will occur 0:12:36.113,0:12:38.336 in the next two years and underestimate 0:12:38.336,0:12:42.212 the change that will occur in the next 10." -- Bill Gates. 0:12:42.212,0:12:43.575 Thanks very much. 0:12:43.575,0:12:46.258 (Applause)