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So let's start with some good news,

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and the good news has to do with what do we know

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based on biomedical research

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that actually has changed the outcomes

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for many very serious diseases?

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Let's start with leukemia,

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acute lymphoblastic leukemia, ALL,

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the most common cancer of children.

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When I was a student,

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the mortality rate was about 95 percent.

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Today, some 25, 30 years later, we're talking about

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a mortality rate that's reduced by 85 percent.

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Six thousand children each year

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who would have previously died of this disease are cured.

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If you want the really big numbers,

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look at these numbers for heart disease.

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Heart disease used to be the biggest killer,

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particularly for men in their 40s.

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Today, we've seen a 63-percent reduction in mortality

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from heart disease --

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remarkably, 1.1 million deaths averted every year.

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AIDS, incredibly, has just been named,

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in the past month, a chronic disease,

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meaning that a 20-year-old who becomes infected with HIV

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is expected not to live weeks, months, or a couple of years,

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as we said only a decade ago,

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but is thought to live decades,

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probably to die in his '60s or '70s from other causes altogether.

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These are just remarkable, remarkable changes

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in the outlook for some of the biggest killers.

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And one in particular

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that you probably wouldn't know about, stroke,

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which has been, along with heart disease,

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one of the biggest killers in this country,

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is a disease in which now we know

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that if you can get people into the emergency room

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within three hours of the onset,

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some 30 percent of them will be able to leave the hospital

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without any disability whatsoever.

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Remarkable stories,

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good-news stories,

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all of which boil down to understanding

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something about the diseases that has allowed us

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to detect early and intervene early.

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Early detection, early intervention,

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that's the story for these successes.

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Unfortunately, the news is not all good.

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Let's talk about one other story

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which has to do with suicide.

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Now this is, of course, not a disease, per se.

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It's a condition, or it's a situation

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that leads to mortality.

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What you may not realize is just how prevalent it is.

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There are 38,000 suicides each year in the United States.

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That means one about every 15 minutes.

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Third most common cause of death amongst people

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between the ages of 15 and 25.

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It's kind of an extraordinary story when you realize

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that this is twice as common as homicide

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and actually more common as a source of death

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than traffic fatalities in this country.

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Now, when we talk about suicide,

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there is also a medical contribution here,

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because 90 percent of suicides

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are related to a mental illness:

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depression, bipolar disorder, schizophrenia,

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anorexia, borderline personality. There's a long list

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of disorders that contribute,

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and as I mentioned before, often early in life.

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But it's not just the mortality from these disorders.

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It's also morbidity.

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If you look at disability,

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as measured by the World Health Organization

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with something they call the Disability Adjusted Life Years,

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it's kind of a metric that nobody would think of

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except an economist,

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except it's one way of trying to capture what is lost

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in terms of disability from medical causes,

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and as you can see, virtually 30 percent

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of all disability from all medical causes

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can be attributed to mental disorders,

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neuropsychiatric syndromes.

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You're probably thinking that doesn't make any sense.

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I mean, cancer seems far more serious.

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Heart disease seems far more serious.

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But you can see actually they are further down this list,

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and that's because we're talking here about disability.

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What drives the disability for these disorders

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like schizophrenia and bipolar and depression?

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Why are they number one here?

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Well, there are probably three reasons.

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One is that they're highly prevalent.

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About one in five people will suffer from one of these disorders

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in the course of their lifetime.

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A second, of course, is that, for some people,

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these become truly disabling,

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and it's about four to five percent, perhaps one in 20.

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But what really drives these numbers, this high morbidity,

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and to some extent the high mortality,

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is the fact that these start very early in life.

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Fifty percent will have onset by age 14,

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75 percent by age 24,

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a picture that is very different than what one would see

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if you're talking about cancer or heart disease,

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diabetes, hypertension -- most of the major illnesses

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that we think about as being sources of morbidity and mortality.

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These are, indeed, the chronic disorders of young people.

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Now, I started by telling you that there were some good-news stories.

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This is obviously not one of them.

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This is the part of it that is perhaps most difficult,

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and in a sense this is a kind of confession for me.

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My job is to actually make sure that we make progress

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on all of these disorders.

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I work for the federal government.

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Actually, I work for you. You pay my salary.

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And maybe at this point, when you know what I do,

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or maybe what I've failed to do,

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you'll think that I probably ought to be fired,

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and I could certainly understand that.

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But what I want to suggest, and the reason I'm here

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is to tell you that I think we're about to be

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in a very different world as we think about these illnesses.

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What I've been talking to you about so far is mental disorders,

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diseases of the mind.

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That's actually becoming a rather unpopular term these days,

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and people feel that, for whatever reason,

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it's politically better to use the term behavioral disorders

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and to talk about these as disorders of behavior.

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Fair enough. They are disorders of behavior,

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and they are disorders of the mind.

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But what I want to suggest to you

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is that both of those terms,

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which have been in play for a century or more,

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are actually now impediments to progress,

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that what we need conceptually to make progress here

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is to rethink these disorders as brain disorders.

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Now, for some of you, you're going to say,

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"Oh my goodness, here we go again.

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We're going to hear about a biochemical imbalance

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or we're going to hear about drugs

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or we're going to hear about some very simplistic notion

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that will take our subjective experience

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and turn it into molecules, or maybe into some sort of

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very flat, unidimensional understanding

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of what it is to have depression or schizophrenia.

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When we talk about the brain, it is anything but

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unidimensional or simplistic or reductionistic.

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It depends, of course, on what scale

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or what scope you want to think about,

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but this is an organ of surreal complexity,

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and we are just beginning to understand

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how to even study it, whether you're thinking about

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the 100 billion neurons that are in the cortex

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or the 100 trillion synapses

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that make up all the connections.

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We have just begun to try to figure out

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how do we take this very complex machine

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that does extraordinary kinds of information processing

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and use our own minds to understand

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this very complex brain that supports our own minds.

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It's actually a kind of cruel trick of evolution

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that we simply don't have a brain

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that seems to be wired well enough to understand itself.

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In a sense, it actually makes you feel that

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when you're in the safe zone of studying behavior or cognition,

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something you can observe,

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that in a way feels more simplistic and reductionistic

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than trying to engage this very complex, mysterious organ

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that we're beginning to try to understand.

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Now, already in the case of the brain disorders

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that I've been talking to you about,

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depression, obsessive compulsive disorder,

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post-traumatic stress disorder,

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while we don't have an in-depth understanding

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of how they are abnormally processed

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or what the brain is doing in these illnesses,

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we have been able to already identify

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some of the connectional differences, or some of the ways

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in which the circuitry is different

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for people who have these disorders.

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We call this the human connectome,

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and you can think about the connectome

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sort of as the wiring diagram of the brain.

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You'll hear more about this in a few minutes.

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The important piece here is that as you begin to look

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at people who have these disorders, the one in five of us

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who struggle in some way,

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you find that there's a lot of variation

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in the way that the brain is wired,

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but there are some predictable patterns, and those patterns

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are risk factors for developing one of these disorders.

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It's a little different than the way we think about brain disorders

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like Huntington's or Parkinson's or Alzheimer's disease

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where you have a bombed-out part of your cortex.

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Here we're talking about traffic jams, or sometimes detours,

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or sometimes problems with just the way that things are connected

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and the way that the brain functions.

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You could, if you want, compare this to,

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on the one hand, a myocardial infarction, a heart attack,

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where you have dead tissue in the heart,

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versus an arrhythmia, where the organ simply isn't functioning

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because of the communication problems within it.

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Either one would kill you; in only one of them

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will you find a major lesion.

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As we think about this, probably it's better to actually go

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a little deeper into one particular disorder, and that would be schizophrenia,

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because I think that's a good case

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for helping to understand why thinking of this as a brain disorder matters.

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These are scans from Judy Rapoport and her colleagues

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at the National Institute of Mental Health

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in which they studied children with very early onset schizophrenia,

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and you can see already in the top

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there's areas that are red or orange, yellow,

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are places where there's less gray matter,

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and as they followed them over five years,

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comparing them to age match controls,

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you can see that, particularly in areas like

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the dorsolateral prefrontal cortex

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or the superior temporal gyrus, there's a profound loss of gray matter.

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And it's important, if you try to model this,

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you can think about normal development

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as a loss of cortical mass, loss of cortical gray matter,

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and what's happening in schizophrenia is that you overshoot that mark,

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and at some point, when you overshoot,

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you cross a threshold, and it's that threshold

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where we say, this is a person who has this disease,

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because they have the behavioral symptoms

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of hallucinations and delusions.

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That's something we can observe.

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But look at this closely and you can see that actually they've crossed a different threshold.

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They've crossed a brain threshold much earlier,

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that perhaps not at age 22 or 20,

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but even by age 15 or 16 you can begin to see

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the trajectory for development is quite different

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at the level of the brain, not at the level of behavior.

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Why does this matter? Well first because,

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for brain disorders, behavior is the last thing to change.

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We know that for Alzheimer's, for Parkinson's, for Huntington's.

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There are changes in the brain a decade or more

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before you see the first signs of a behavioral change.

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The tools that we have now allow us to detect

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these brain changes much earlier, long before the symptoms emerge.

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But most important, go back to where we started.

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The good-news stories in medicine

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are early detection, early intervention.

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If we waited until the heart attack,

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we would be sacrificing 1.1 million lives

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every year in this country to heart disease.

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That is precisely what we do today

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when we decide that everybody with one of these brain disorders,

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brain circuit disorders, has a behavioral disorder.

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We wait until the behavior becomes manifest.

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That's not early detection. That's not early intervention.

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Now to be clear, we're not quite ready to do this.

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We don't have all the facts. We don't actually even know

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what the tools will be,

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nor what to precisely look for in every case to be able

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to get there before the behavior emerges as different.

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But this tells us how we need to think about it,

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and where we need to go.

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Are we going to be there soon?

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I think that this is something that will happen

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over the course of the next few years, but I'd like to finish

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with a quote about trying to predict how this will happen

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by somebody who's thought a lot about changes

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in concepts and changes in technology.

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"We always overestimate the change that will occur

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in the next two years and underestimate

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the change that will occur in the next 10." -- Bill Gates.

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Thanks very much.

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(Applause)