WEBVTT

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This is the first time I've ever
followed Pinky the Mouse.

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(Laughter)

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If nothing else should tell you
that science can be fun,

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science can be counter-intuitive,
science can blow your mind,


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and what I'm going to do
in the next few minutes

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is to tell you
that science can also save lives.

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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 we know based on biomedical research

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that actually has changed the outcomes
for many very serious diseases.

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Start with Leukemia,
acute lymphoblastic leukemia, ALL,

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the most common cancer of children.

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When I was a student,
the mortality rate was about 95%.

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Today, some 25, 30 years later,
we are talking about

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a mortality rate is reduced by 85%.

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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 the numbers for heart disease.

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Heart disease used to be
the biggest killer

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particularly men in their 40s.

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Today we've seen a 63% reduction
in mortality 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 years 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 for 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 of some
of the biggest killers.

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One in particular that
you probably wouldn't know about,

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stroke, which has been,
along with heart disease,

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one of the biggest killers in the country
along with cancer,

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is a disease we know now
if you can get people into the hospital,

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into the emergency room
within three hours of the onset,

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some 30% of them will leave the hospital
without any disabilities whatsoever.

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Remarkable stories, good news stories,
all of which boil down to

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understanding something about the diseases
that has allowed us


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to detect early and intervene early.

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Early detection and early intervention.

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That's the story for these successes
across the board.

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And it tells you how biomedical research

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can really change the picture
for millions and millions of people.

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Unfortunately the news is not all good.

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Let's talk about one other story
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 a situation
that leads to mortality.

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Which you may not realize
is how prevalent it is today.

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

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That means one in about 15 minutes.

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The third most common cause of death
among people between 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,
there is also a medical contribution here.

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Because 90% of suicides
are related to a mental illness,

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depression, bipolar disorder,
schizophrenia,

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anorexia, borderline personality,

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there's a long list of disorders
that contribute,

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and as I mentioned before,
often early in life.

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

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It's also morbidity.
If you look at disability,

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here as measured
by the World Health Organization,

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something they called
"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%
of all disabilities

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from all medical causes

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can be attributed to mental disorders
or neuro psychiatric 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're
further down this list.

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That is because
we are talking about disability.

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What drives disability
for these disorders like

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schizophrenia and
bipolar disorder and depression?

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Why are they number one here?

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Probably there are three reasons.

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One is that they're highly prevalent.

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About one in five people will suffer

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from one of these disorders
in the course of their life time.

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The second of course is that 
for some people

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these become truly disabling.

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It's about 4 to 5%,

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that's one in 20, are truly disabled
by one of these illnesses.

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But what really drives these numbers,

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this high morbidity 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, 75% by age 24.

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A picture that is very different
from that what one would see

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if we are talking about cancer
or heart disease, diabetes, hypertension,

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most of the major illnesses
that we think about,

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as being sources
of mobility 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 are some good news stories.

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This is obviously not one of them.

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This is the part of what is,

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perhaps the most difficult since

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this is kind of confession for me.

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My job is to actually make sure

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that we make progress
on all of these disorders,

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because I work for the Federal Government.

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I actually work for you.
You pay my salary.

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Maybe at this point,
when you know what I do

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or maybe what I've failed to do,
you'll think I probably ought to be fired.

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I could certainly understand that.

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But what I want to suggest,

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and the reason I am here is to tell you

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that I think we are about to be
in a very different world

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as we think about these illnesses.

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And that is, to some extent,
going to be dependent

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on the work you'll hear about today.

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That's going to be really exciting,

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technically truly transformative.

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But the point I want to make is that

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the most important transformation here
is a conceptual one.

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What I've been
talking to you about so far

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is mental disorders, 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 the 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
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 a progress here

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is to rethink these disorders
as brain disorders.

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Now some of you are going to say,


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"Oh my goodness. Here we go again,

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We are going to hear about
biochemical imbalance.

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We are going to hear about drugs.

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We are going to hear about
some very simplistic notion,

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that will take our subjective experience
and turn it into molecules,

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or maybe into some sort of very flat
uni-dimensional understanding

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of what it is to have
depression or schizophrenia."

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Over the course of the day

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you are going to hear
that when we talk about the brain

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it is anything but uni-dimensional,
or simplistic or reductionistic.

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It depends, of course, on what scale

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or what scope you 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,

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whether you are thinking about
a hundred billion neurons in the cortex

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or a hundred 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 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 the very complex brain

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that supports it,
that supports our own mind.

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It's actually 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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But we are making progress,
and because of some of the technologies

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you hear about today,

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we are actually able to begin
to string this together.

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In a sense it actually makes you feel that

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when you are in a safe zone studying
behavior and 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
and mysterious organ

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that we are beginning
to try to understand.

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Now already in a 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,
post traumatic stress disorder,

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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 those illnesses.

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We've been able to already identify
some of the connectional differences.

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Some of the ways of 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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You can think about Connectome,
as the wiring diagram of the brain.

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You'll hear more about it
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,

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the one in five of us
who struggle in some way,

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you'll find that there's
a lot of variation

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in the way the brain is wired
but there are some predictable patterns.

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Those patterns are risk factors

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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, 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 are talking about traffic jams
or sometimes detours

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or sometimes problems with
just the way things are connected

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and the way 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 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,

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and in only one of them
will you find a major lesion.

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As we think about this,

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maybe it's better to actually go

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a little deeper
into one particular disorder.

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That would be schizophrenia.

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I think that's a good case
for helping to understand

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why thinking of this
as a brain disorder matters.

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Schizophrenia is a disorder
that generally comes on by

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in terms of the psychotic symptoms,

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which is the way we diagnose it,

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delusions, hallucination,
problems with thinking

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problems with attention,

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generally around age of 18 to 22, 23, 24.

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These are scans from Judie 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 there are areas

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that are red, orange and yellow,

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there's places with less gray matter.

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And as they follow them over 5 years

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comparing them
to age-match controls,

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you can see that, particularly in areas

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like the dorsal lateral prefrontal cortex

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or the superior temporal gyrus,

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there is a profound loss of gray matter.

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This is important.

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It's important if you try to model this.

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You can think about

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normal development
as a loss of cortical mass,

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loss of cortical gray matter.

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What's happening in schizophrenia

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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.

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You can see that actually
they've crossed a different threshold.

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They crossed a brain threshold
much earlier.

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That perhaps not at the age 22 or 20

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but even by age 15 or 16,

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you can begin to see that 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?

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

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We know that for Alzheimer's,
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 we have, and you'll hear
much more about this

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in the course of the day,

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they are getting better every year,

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now allow us to detect
these brain changes much earlier,

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long before the symptoms emerge.

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But most importantly,
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 are not quite ready to do this.

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We don't have all the facts.

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We don't actually even know
what the tools would be

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nor what to precisely look for
in every case.

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to be able to get there
before the behavior emerges as different.

00:14:27.741 --> 00:14:31.357
But this tells us how we need
to think about it and where we need to go.

00:14:31.357 --> 00:14:32.985
Are we going to be there soon?

00:14:32.985 --> 00:14:35.711
I think that this is something
that will happen

00:14:35.711 --> 00:14:38.019
over the course of the next few years

00:14:38.019 --> 00:14:40.033
but I'd like to finish with the quote

00:14:40.033 --> 00:14:42.231
about trying to predict
how this will happen,

00:14:42.231 --> 00:14:44.815
by somebody who's thought a lot
about changes

00:14:44.815 --> 00:14:46.647
in concepts
and changes in technology.

00:14:46.647 --> 00:14:50.126
"We always overestimate the change
that will occur in the next two years

00:14:50.126 --> 00:14:52.776
and underestimate the change

00:14:52.776 --> 00:14:55.656
that will occur in the next ten." Bill Gates.

00:14:55.656 --> 00:14:57.377
Thanks very much.

00:14:57.377 --> 00:14:59.321
(Applause)