This is the first time I've ever followed Pinky the Mouse.
(Laughter)
If nothing else should tell you that science can be fun,
science can be counter-intuitive, science can blow your mind,
and what I'm going to do in the next few minutes
is to tell you that science can also save lives.
So let's start with some good news.
And the good news has to do with what we know based on biomedical research
that actually has changed the outcomes for many very serious diseases.
Start with Leukemia, acute lymphoblastic leukemia, ALL,
the most common cancer of children.
When I was a student, the mortality rate was about 95%.
Today, some 25, 30 years later, we are talking about
a mortality rate is reduced by 85%.
Six thousand children each year
who would have previously died of this disease are cured.
If you want the really big numbers,
look at the numbers for heart disease.
Heart disease used to be the biggest killer
particularly men in their 40s.
Today we've seen a 63% reduction in mortality from heart disease.
Remarkably 1.1 million deaths averted every year.
AIDS, incredibly has just been named
in the past month a chronic disease,
meaning that a 20 years old who becomes infected with HIV
is expected not to live weeks, months or a couple of years,
as we said only a decade ago,
but is thought to live for decades,
probably to die in his 60s or 70s from other causes altogether.
These are just remarkable, remarkable changes,
in the outlook of some of the biggest killers.
One in particular that you probably wouldn't know about,
stroke, which has been, along with heart disease,
one of the biggest killers in the country along with cancer,
is a disease we know now if you can get people into the hospital,
into the emergency room within three hours of the onset,
some 30% of them will leave the hospital without any disabilities whatsoever.
Remarkable stories, good news stories, all of which boil down to
understanding something about the diseases that has allowed us
to detect early and intervene early.
Early detection and early intervention.
That's the story for these successes across the board.
And it tells you how biomedical research
can really change the picture for millions and millions of people.
Unfortunately the news is not all good.
Let's talk about one other story which has to do with suicide.
Now this is of course not a disease per se.
It's a condition or a situation that leads to mortality.
Which you may not realize is how prevalent it is today.
There are 38,000 suicides each year in the United States.
That means one in about 15 minutes.
The third most common cause of death among people between ages of 15 and 25.
It's kind of an extraordinary story when you realize
that this is twice as common as homicide,
and actually more common as a source of death
than traffic fatalities in this country.
Now when we talk about suicide, there is also a medical contribution here.
Because 90% of suicides are related to a mental illness,
depression, bipolar disorder, schizophrenia,
anorexia, borderline personality,
there's a long list of disorders that contribute,
and as I mentioned before, often early in life.
And it's not just the mortality from these disorders.
It's also morbidity. If you look at disability,
here as measured by the World Health Organization,
something they called "Disability Adjusted Life Years."
It's kind of a metric that nobody would think of
except an economist.
Except it's one way of trying to capture what is lost
in terms of disability from medical causes.
And as you can see virtually 30% of all disabilities
from all medical causes
can be attributed to mental disorders or neuro psychiatric syndromes.
You're probably thinking that doesn't make any sense.
I mean cancer seems far more serious.
Heart disease seems far more serious.
But you can see actually they're further down this list.
That is because we are talking about disability.
What drives disability for these disorders like
schizophrenia and bipolar disorder and depression?
Why are they number one here?
Probably there are three reasons.
One is that they're highly prevalent.
About one in five people will suffer
from one of these disorders in the course of their life time.
The second of course is that for some people
these become truly disabling.
It's about 4 to 5%,
that's one in 20, are truly disabled by one of these illnesses.
But what really drives these numbers,
this high morbidity and to some extent the high mortality,
is the fact that these start very early in life.
Fifty percent will have onset by age 14, 75% by age 24.
A picture that is very different from that what one would see
if we are talking about cancer or heart disease, diabetes, hypertension,
most of the major illnesses that we think about,
as being sources of mobility and mortality.
These are indeed the chronic disorders of young people.
Now I started by telling you that there are some good news stories.
This is obviously not one of them.
This is the part of what is,
perhaps the most difficult since
this is kind of confession for me.
My job is to actually make sure
that we make progress on all of these disorders,
because I work for the Federal Government.
I actually work for you. You pay my salary.
Maybe at this point, when you know what I do
or maybe what I've failed to do, you'll think I probably ought to be fired.
I could certainly understand that.
But what I want to suggest,
and the reason I am here is to tell you
that I think we are about to be in a very different world
as we think about these illnesses.
And that is, to some extent, going to be dependent
on the work you'll hear about today.
That's going to be really exciting,
technically truly transformative.
But the point I want to make is that
the most important transformation here is a conceptual one.
What I've been talking to you about so far
is mental disorders, diseases of the mind.
That's actually becoming a rather unpopular term these days.
And people feel that, for whatever the reason,
it's politically better to use the term "behavioral disorders",
and to talk about these as disorders of behavior.
Fair enough, they are disorders of behavior
and they are disorders of the mind.
But what I want to suggest to you is that both of those terms
which have been in play for a century or more,
are actually now impediments to progress.
That what we need conceptually to make a progress here
is to rethink these disorders as brain disorders.
Now some of you are going to say,
"Oh my goodness. Here we go again,
We are going to hear about biochemical imbalance.
We are going to hear about drugs.
We are going to hear about some very simplistic notion,
that will take our subjective experience and turn it into molecules,
or maybe into some sort of very flat uni-dimensional understanding
of what it is to have depression or schizophrenia."
Over the course of the day
you are going to hear that when we talk about the brain
it is anything but uni-dimensional, or simplistic or reductionistic.
It depends, of course, on what scale
or what scope you think about.
But this is an organ of surreal complexity.
And we are just beginning to understand,
how to even study it,
whether you are thinking about a hundred billion neurons in the cortex
or a hundred trillion synapses
that make up all the connections.
We have just begun to try to figure out
how we take this very complex machine
that does extraordinary kinds of information processing
and use our own minds to understand the very complex brain
that supports it, that supports our own mind.
It's actually kind of cruel trick of evolution
that we simply don't have a brain
that seems to be wired well enough to understand itself.
But we are making progress, and because of some of the technologies
you hear about today,
we are actually able to begin to string this together.
In a sense it actually makes you feel that
when you are in a safe zone studying behavior and cognition,
something you can observe,
that in a way feels more simplistic and reductionistic
than trying to engage this very complex and mysterious organ
that we are beginning to try to understand.
Now already in a case of the brain disorders
that I've been talking to you about,
depression, obsessive compulsive disorder, post traumatic stress disorder,
we don't have an in-depth understanding
of how they are abnormally processed
or what the brain is doing in those illnesses.
We've been able to already identify some of the connectional differences.
Some of the ways of which the circuitry is different
for people who have these disorders.
We call this the "Human Connectome."
You can think about Connectome, as the wiring diagram of the brain.
You'll hear more about it in a few minutes.
The important piece here is that as you begin to look
at people who have these disorders,
the one in five of us who struggle in some way,
you'll find that there's a lot of variation
in the way the brain is wired but there are some predictable patterns.
Those patterns are risk factors
for developing one of these disorders.
It's a little different than the way we think about brain disorders
like Huntington's, Parkinson’s or Alzheimer's disease
where you have a bombed out part of your cortex.
Here we are talking about traffic jams or sometimes detours
or sometimes problems with just the way things are connected
and the way the brain functions,
you could if you want compare this to,
on the one hand, a myocardial infarction - a heart attack
where you have dead tissue in the heart
versus arrhythmia where the organ simply isn't functioning
because of the communication problems within it.
Either one would kill you,
and in only one of them will you find a major lesion.
As we think about this,
maybe it's better to actually go
a little deeper into one particular disorder.
That would be schizophrenia.
I think that's a good case for helping to understand
why thinking of this as a brain disorder matters.
Schizophrenia is a disorder that generally comes on by
in terms of the psychotic symptoms,
which is the way we diagnose it,
delusions, hallucination, problems with thinking
problems with attention,
generally around age of 18 to 22, 23, 24.
These are scans from Judie Rapoport and her colleagues
at the National Institute of Mental Health,
in which they studied children with very early onset schizophrenia.
And you can see already in the top there are areas
that are red, orange and yellow,
there's places with less gray matter.
And as they follow them over 5 years
comparing them to age-match controls,
you can see that, particularly in areas
like the dorsal lateral prefrontal cortex
or the superior temporal gyrus,
there is a profound loss of gray matter.
This is important.
It's important if you try to model this.
You can think about
normal development as a loss of cortical mass,
loss of cortical gray matter.
What's happening in schizophrenia
is that you overshoot that mark
and at some point when you overshoot
you cross a threshold, and it's that threshold
where we say this is a person who has this disease
because they have the behavioral symptoms,
of hallucinations and delusions.
That's something we can observe.
But look at this closely.
You can see that actually they've crossed a different threshold.
They crossed a brain threshold much earlier.
That perhaps not at the age 22 or 20
but even by age 15 or 16,
you can begin to see that the trajectory for development is quite different
at the level of the brain not at the level of behavior.
Why does this matter?
Well first because for brain disorders, behavior is the last thing to change.
We know that for Alzheimer's, Parkinson's, for Huntington's.
There are changes in the brain a decade or more
before you see the first signs of a behavioral change.
The tools we have, and you'll hear much more about this
in the course of the day,
they are getting better every year,
now allow us to detect these brain changes much earlier,
long before the symptoms emerge.
But most importantly, go back to where we started.
The good news stories in medicine
are early detection, early intervention.
If we waited until the heart attack
we would be sacrificing 1.1 million lives
every year in this country to heart disease.
That is precisely what we do today.
When we decide that everybody with one of these brain disorders,
brain circuit disorders, has a behavioral disorder
we wait until the behavior becomes manifest.
That's not early detection. That's not early intervention.
Now to be clear, we are not quite ready to do this.
We don't have all the facts.
We don't actually even know what the tools would be
nor what to precisely look for in every case.
to be able to get there before the behavior emerges as different.
But this tells us how we need to think about it and where we need to go.
Are we going to be there soon?
I think that this is something that will happen
over the course of the next few years
but I'd like to finish with the quote
about trying to predict how this will happen,
by somebody who's thought a lot about changes
in concepts and changes in technology.
"We always overestimate the change that will occur in the next two years
and underestimate the change
that will occur in the next ten." Bill Gates.
Thanks very much.
(Applause)