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