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Meredith Drosback: Good afternoon and welcome
to the White House BRAIN Conference.
I'm Meredith Drosback and I work in the Science Division here
at the White House Office of Science and Technology Policy.
When the president launched the BRAIN Initiative a year
and a half ago, it was with full knowledge that it would take
an all hands on deck effort to meet the bold challenge
he laid before us.
That's why it's great to see so many scholars,
innovators, clinicians, and philanthropists here
in the room today and online answering that call.
Before we dive into our program this afternoon,
I have a couple of housekeeping notes.
We encourage you to follow along our conversation on Twitter
using the hashtag "WHBrain."
During our Q&A with each panel, we will be taking questions
from the audience.
So please look for staffers roaming with notecards
and pens to submit your questions for the panelists.
It is with great pleasure that I welcome you here
to the White House.
I look forward to our discussion and I hope that
each of us leaves here today with a new idea
on how we can play a role in making this collaborative
endeavor a success.
With that, I'd like to introduce our first speaker.
Daria Nesterovich is a graduate student
at the University of Utah where her primary research interest
is neural engineering applied to neural prosthetics,
specifically deep brain stimulation
for Parkinson's disease.
She graduated from Duke University this past spring as a
Pratt Engineering Fellow and a National Academy of Engineering
Grand Challenge Scholar with a major in biomedical engineering
and minor in neuroscience.
We're so happy to have Daria here today as part of the White
House BRAIN Conference and to tell us a little bit about
her experiences before introducing our next speaker.
Please join me in welcoming Daria.
(applause)
Daria Nesterovich: All right.
As a current graduate student in neural engineering,
I am honored to represent the National Academy of Engineering
Grand Challenge Scholars program and graduate students nationwide
working to advance our understanding of the brain.
Thanks to the BRAIN Initiative and the resulting excitement
around neural research, the field of neural engineering
is currently experiencing unprecedented funding which
encouraged me to pursue a PhD in the field.
The stark reality of science is that funding is often scarcer
than many of us would like it to be.
This in turn slows down research progress and prevents the goals
of large-scale projects from coming to fruition.
However, the BRAIN Initiative has already led to the
investment of substantial funding in that the ambitious
and necessary goals of mapping the brain,
linking neural activity to behavior,
and integrating computation within neuroscience experiments.
With a background in biomedical engineering and neuroscience,
I earned my bachelor's at Duke University before starting my
PhD with Dr. Alan Dorval in the neural interfaces track in the
bioengineering program at the University of Utah as a part
of the National Academy of Engineering Grand Challenge
Scholars program, which a colleague of mine will describe
later this afternoon.
I joined Dr. Warren Grill's neuroprosthesis laboratory
at Duke during my freshman year.
Our research focused on deep brain stimulation,
a neural prosthetic treatment for the motor symptoms
of Parkinson's disease.
Despite the disease having been defined for nearly 200 years,
we still have a very poor understanding as to its causes,
how to slow its progression, and how to prevent it.
The BRAIN Initiative is the needed push to not only bring
such neural degenerative diseases to the forefront
of society's attention, but to also build large collaborations
between research groups, national laboratories,
foundations, and companies to actively work
towards a solution.
DBS has rapidly become the primary surgical intervention
for Parkinson's disease, but due to the thousands of parameter
combinations and the potential for adverse side effects,
it is very difficult to program DBS quickly and efficiently.
These difficulties highlight one small example as to why the
National Academy of Engineering chose reverse engineer the brain
as one of society's engineering challenges of the century.
Like many participants here, I want to dedicate my career
to help solve this challenge [spelled phonetically].
In graduate school, I'm continuing my work on DBS
with the goal of improving treatment efficacy.
A problem with DBS that we still see today is that even with
the most advanced surgical method -- methods,
it is not uncommon for surgeons to miss the center of their
target by several millimeters, a distance significant
given such a small target for electrode insertion.
To combat this, the Dorval group has developed a current steering
electrode that allows the applied current from misplaced
electrodes to be reshaped to the target area.
My part of the project involves creating programming algorithms
that incorporate data from MRI images for -- to allow
clinicians to automatically program the 10,000
contacts to optimize stimulation for
each patient individually.
When fully complete, we anticipate that our design will
greatly reduce side effects for DBS while simultaneously
improving motor function to a higher degree
and in a larger percentage of the patient population.
As part of the BRAIN Initiative, understanding the brain's
connectivity on a larger scale will only lead to a better
understanding of Parkinson's disease,
which in turn enables our research practices and
approaches to be improved.
The investments made through the BRAIN Initiative will lead
to marked improvements in our understanding of the brain,
our prevention of neurological disorders,
and our treatment of those who have such diseases.
Our collective work has the ability to improve the quality
of life of countless Americans and their loved ones.
With that in mind, I'm now privileged to introduce
our opening speaker, Dr. John Holdren,
Assistant to the President for Science and Technology
and director of the White House
Office of Science and Technology Policy.
It is due to his leadership in advancing the science and
engineering enterprise in the United States that all
of us are here today.
Dr. Holdren and the Office of Science and Technology Policy
have led the charge to meet the challenge
of the BRAIN Initiative and to fulfill the president's
vision of a better understanding of the human brain.
I feel honored to be a part of this exciting initiative
with each and every one of you here today.
Thank you.
(applause)
John Holdren: Well, thank you, Daria,
and let me add a warm welcome on behalf of President Obama
to all of you to this first ever White House BRAIN Conference.
Before going further, I want to add -- I want to offer some
thanks to some key folks who are represented in this room and
I want to start with two of my favorite members of Congress --
very strong supporters of science and technology
in the Congress.
Congresswoman Eddie Bernice Johnson,
who is the ranking member of the House Committee on Science,
Space, and Technology --
(applause)
And Congressman Chaka Fattah who is the ranking member of the
Commerce, Justice, and Science Appropriations Subcommittee,
which happens to control my budget as well as a good
many other important ones.
And Congressman Fattah has been a tireless supporter
of initiative and innovation in neurotechnology
and neuroscience in particular.
Congressman Fattah.
(applause)
Next, I want to thank my administration colleagues at
NIH, at DARPA, at NSF, FDA, and IARPA who have spent so much
time building and shaping this effort into a program that
I think this really going to make a positive difference.
Your continued partnership is going to be essential going
forward and I particularly want to recognize from the NIH,
Dr. Story Landis, director
of the National Institute of Neurological Disorders
and Stroke.
Where is Dr. Landis?
(applause)
And the director of the National Science Foundation,
Dr. France Cordova who is down in the front row.
(applause)
I want to acknowledge as well the Department of Energy,
which is starting to explore the role that its national labs
can play in accelerating progress in brain research.
And of course I want to recognize the many
organizations -- private sector, philanthropic,
civil society organizations, a lot of them represented here
today, that have stepped up, that have answered the
president's call to action to support the goals
of the BRAIN Initiative.
And last, to everybody in attendance here and to those
watching on the webcast, thanks for joining us at this
first ever White House Brain Conference.
You know by now that the BRAIN Initiative has emerged as one
of the administration's top research priorities.
In fact, President Obama identified it as one
of his administration's grand challenges.
Those are 21st century versions of moon shots -- audacious but
achievable goals to solve tough problems
and spark game-changing innovations.
The BRAIN Initiative is all about accelerating the kinds
of research, discovery, and innovative technology
applications that can help build a dynamic understanding
of how the brain works.
One of its aims obviously is to build the tools and technologies
that researchers will need to uncover the mysteries
of brain disorders, which today, as we all know,
afflict American families and people around the world --
disorders such as Alzheimer's, Parkinson's disease, depression,
and traumatic brain injury.
These and other neurological and psychiatric diseases
of the brain exact a staggering toll on our society.
Today, 100 million Americans suffer from brain disorders
at some point in their lives and that number
is expected to grow as our nation's population grows.
In addition to getting a better handle on the mechanisms
of disorder and potential courses of treatment,
the BRAIN Initiative is aiming to revolutionize our
understanding of phenomena such as learning, memory, perception,
action, and self-awareness, all of which arise from the nearly
100 billion neurons and 100 trillion connections
that exist inside our brains.
Thus far, scientific enterprise, scientific innovation has
brought us a long way toward better understanding certain
disease mechanisms and learning and behavioral patterns.
In the last decade alone, scientists have made a number
of landmark discoveries that today are creating new
opportunities to unlock the mysteries of the mind.
These include the sequencing of the human genome,
the development of new tools for mapping neuronal connections,
increasing resolution of imaging technologies,
the maturation of nanoscience, and the rise
of biological engineering.
These breakthroughs have paved the way for unprecedented
collaboration and discovery across scientific fields.
For instance, by combining advanced genetic and optical
techniques, scientists can now use pulses of light to determine
how specific cell activities in the brain affect behavior.
Similarly, through the integration of neuroscience
and physics, researchers can now use high resolution imaging
technologies to observe how the brain is structurally
and functionally connected in living humans.
Nevertheless, and again, I think everybody in the room knows
this, we have a long way to go to achieve the full,
clear picture of how the human brain functions
at the speed of thought.
The kinds of breakthroughs we're looking for in terms of how
we treat neurological and psychiatric disease and how we
foster better learning outcomes will require a new generation
of tools and technologies that enable researchers to record
signals from vastly greater numbers of brain cells
at vastly greater speeds.
A key barrier to such progress has been the lack of available
and effective tools to study the brain in action.
Today, for instance, researchers cannot adequately measure
the real time interactions of neural circuits.
The technologies required to do so with accuracy
simply don't exist.
This is the particular grand challenge that the BRAIN
Initiative seeks to address.
It's a big challenge, but the administration and President
Obama believe it's an achievable -- an achievable goal.
No water up here.
(laughter)
I'm going to steal Dr. Paul Alivisatos's as well.
(laughter)
My apologies, Paul.
(laughter)
I bet we can get you a refill.
Paul Alivisatos: It's important for you to have it.
(laughter)
By working together, we can both the combat the suffering that is
caused by brain disorders and position the United States
as a leader in discovering, building, and bringing to market
the tools and technologies needed to do so.
President Obama has said that America can accomplish anything
we set our mind to.
This is a great example of a place to prove that.
Indeed, the people in this room and the new commitments being
announced today are a testament to our determination and I'm
really thrilled to be able to acknowledge those investments
now and more will be said about them later by Tom Kalil.
But altogether, the research community, federal agencies,
foundations, patient advocacy groups,
private research institutes, companies, scientific societies,
and individual scientists are aligning more than $300 million
in commitments to support the president's BRAIN Initiative.
That's in addition to the more than $100 million
in commitments made last April when the president
first launched the initiative.
I'm also encouraged that top neuroscientists have developed
a 12-year research strategy to help chart a course for
the NIH's contribution to the BRAIN Initiative.
These investments and this strategic vision will propel
us forward in this very ambitious endeavor.
Just imagine if no family had to grapple with the helplessness
and heartache of a loved one with Parkinson's
or traumatic brain injury.
Imagine if Alzheimer's or ALS or chronic depression were
eradicated in our lifetimes.
And imagine if you, the people in this room,
contributed to those breakthroughs.
I think you will.
One of our nation's next great frontiers is the three pound
mass between our ears.
(laughter)
With your help, we are poised to continue the great American
tradition of expanding the horizons of human knowledge
through research, science, and innovation.
So again, let me just extend my congratulations to all who are
taking part in this amazing work and for the game-changing
discoveries and innovations that are sure to emerge
from our collective efforts.
Let's get to it.
Thank you very much.
(applause)
Meredith Drosback: Thank you, Dr. Holdren.
Our first panel of speakers will be talking with us about the
cutting edge technology and tools needed to meet the BRAIN
Initiative goals and to address human health challenges.
To kick off this discussion, we have Dr. Paul Alivisatos.
Paul is an award-winning chemist,
an internationally recognized authority on the fabrication of
nanocrystals, and their use in renewable energy applications.
He is the director of the Lawrence Berkeley National
Laboratory and holds a joint appointment as a professor of
chemistry at UC Berkeley where he continues to teach
and mentor an active student research program.
Please join me in welcoming Paul.
(applause)
Paul Alivisatos: Well, thank you so much.
It's such an exciting event that we have going here and we're
going to have two panels in the next hour that are going
to discuss aspects of the BRAIN Initiative.
And the first panel is going to really be focused on the
exciting opportunity and as well as the challenges that are there
from the point of view of the science and technology.
I think we all know that this is a field where there's
just really very exciting, challenging,
and no doubt extremely beautiful science that can happen and one
of the underlying questions that we'll be exploring here is what
is special about this moment?
Why should there be a BRAIN Initiative now?
Have there been developments within neuroscience and within
all the related disciplines or even disciplines that can
ultimately support neuroscience that make
this a very special moment?
And we're very, very fortunate to have here two really
wonderful panelists, Professor Cori Bargmann from the
Rockefeller University and of the Howard Hughes Medical
Institute and Professor Mark Schnitzer from Stanford
and also of the Howard Hughes Medical Institute.
So we're so fortunate to have you here and so let's start
our panel here with Professor Bargmann.
Professor Bargmann, your work has mapped the neural circuits
in the nematode worm and observations related to those --
to the behaviors of the worm.
So in many ways, we could say that you have laid the
groundwork for the BRAIN Initiative.
(laughter)
And so we're going to look to you first to give us some
insights on this field and where you see it going.
Cornelia Bargmann: Okay.
Thank you, Paul.
So the goal of the BRAIN Initiative is to map the
circuits of the brain, to measure the fluctuating patterns
of electrical and chemical activity in those circuits,
and to understand how their interplay creates our
unique cognitive and behavioral abilities.
And this is a special time to be working on this because we can
really build on the neuroscience that's accumulated over the past
50 years that really accumulated in two different areas,
one of which was the level of molecules and individual
neurons, so the level of sort of a very high resolution
magnified understanding of neural processes,
and the other was from neurology and from brain imaging,
the sort of understanding of large areas
of the human brain and how those work.
But there's been a missing level in the middle and that missing
level in the middle is really where we think that cognitive
processes and processes like perception and memory and action
are developing, and that's not at single neurons and not at
sort of large blobs, but at networks of, in a human brain,
millions of neurons that are acting together locally and over
great distances whose dynamics are constantly changing
and the flow of information of neuron from what to the next
and the transformation of this information by context
or by emotional state or by experience gives rise
to the incredible diversity of properties that a brain has.
Now, what makes this the moment is that there have been advances
in three areas that are making it possible to start to look
at the brain at that level -- of the intermediate level
of circuits and networks.
And Paul asked me to talk also about the gaps in our
understanding, and I would say that each of those three areas
gives promise but also points out what still needs to be
accomplished and what the people in this room will have,
I think, a great deal to do in terms of accomplishing.
So the first is that now, instead of looking at the
activity of individual neurons one at a time,
neuroscientists can routinely look at hundreds of neurons
and some people can look at thousands of neurons at a time.
And that is already showing us things about patterns
of activity in the brain that we really did not anticipate
from looking at neurons in isolation.
And that's been an advance driven by new advances in
molecular tools and new kinds of materials for recording,
but we don't need hundreds of neurons.
We really need thousands to millions and there need
to be incredible advances in optics to gather
that information at speed.
There need to be advances -- the tools we have are still --
need to be a hundred times better than they are now.
The second is that once you see these patterns of activity,
if you start to look now at the sorts of things people see --
there's a wonderful movie of the brain of a zebra fish and all
these neurons are flashing on and off and the first thing
you realize is that you have no idea what it means.
(laughter)
And that really -- you know, that one minute movie poses the
questions that you have to solve in parallel with just looking
at patterns of activity, and that is you have to know what
the cells are and you have to know how they're connected
to each other.
And so moving downward to that level of understanding
where the activity comes from is really critical.
And again, this is something that's been done in the past but
is now going to have to be done on a scale that is so much
larger than it's ever been done for,
and when we think about these kinds of reconstructions,
the kinds of data analysis, and image recognition work that's
happening now in the technology world can be brought to bear
on these problems in new ways that will advance them.
And finally, information flow through these systems --
just observing is not understanding.
And in order to understand that, we have to be able
to intervene, to perturb the flow of information,
to see which parts of that activity are really critical for
particular behavioral cognitive states,
and we need to ask also how small perturbations cause the
whole pattern of neural activity to shift.
And this is, again, an area where there's been just
a lot of advance in recent years in the development
of the method called optogenetics for example that
allows manipulation of neural activity, but this needs
to be so much more precise and so much
faster than it is now to really start to interface
with neural circuits in real time.
And then meaning also comes from conceptual approaches
from modeling, from theory, and computation.
And those, again, are areas where we need people from the
quantitative sciences, from statistics, from physics,
from technology, to think with us about how to develop
an understanding beyond a description of the brain.
And I think very close relationships between
experimentalists and theorists are going to become more
and more important as this moves on.
So these are -- in each case, they're opportunities and in
each case they're gaps, and I think this group of people
stands to do a great deal to bring those opportunities
and those gaps to the next stage.
Paul Alivisatos: Okay.
Thank you very much.
We'll turn now to Professor Schnitzer who has really --
if you haven't seen his work previously has built miniature
optical systems that allow his colleagues and himself to --
that can be mounted essentially on an animal to peer inside
their brains of mammals as they go about
their business, (laughs).
And indeed, those miniature optical systems have, you know,
exploited the remarkable discoveries of your colleague
at Stanford, Karl Diesseroth in optogenetics,
which Professor Bargmann was just referring to,
to even modify these behaviors with light.
And so these are really incredible examples of how light
is being used to interrogate.
And so we'd like to hear from you a little bit about this
question of what is special about this moment.
Mark Schnitzer: Yeah, thank you Paul.
First of all, I'd like to thank all the leaders who made
possible not only this event, but also the BRAIN Initiative.
I think Cory laid out some of the key opportunities
and challenges that we face in this initiative,
and I -- and speaking as an engineer,
I think it's a very exciting moment to bring together many of
the elements that she mentioned to [spelled phonetically] the
exciting developments that have come to fruition recently
in different sectors of the engineering world
and of the technological communities.
One of the most exciting things that's happened already in the
BRAIN Initiative has been the energy and enthusiasm it has
evoked within the engineering, information technology,
and physical science communities in academic institutions
and in industrial communities.
And we see this in students and in senior researchers who
probably never thought of themselves as being involved
in neuroscience until recently but are now beginning to ask
how can they help and how can they get involved?
And so as Cori described, I think there are many important
roles for engineering and new technology that will likely
emerge in the BRAIN Initiative and I expect the results will
be profound by helping to unlock some of the central mysteries
of brain function, by providing new tools in helping to lay
the basis for conceptual foundations in our efforts
to prevent and cure brain disease and brain disorders,
and also in harnessing some of the brain's computational
strategies for humanity's own technological purposes.
And part of the reason that this is a very opportune moment for
the BRAIN Initiative is that there already exists many
different dazzling technologies that our engineers and
technological industries have already developed,
and I think that an important part of the BRAIN Initiative
will be harnessing these impressive technologies from
different disciplines and sectors and putting them
to use to new purpose in brain research.
And so just to suggest a few examples of technologies that
have emerged recently that I think may have a very promising
future for brain research -- just to suggest a few.
In telecommunications, we already have very powerful
wireless technologies and these are poised to yield new methods
of wireless brain recording.
Image sensors and miniaturized optics in cell phone cameras
are prompting new forms of tiny microscopes for
inspecting brain activity.
In semiconductor microfabrication,
there are very exciting opportunities to create
customized photonic detectors and sensors that may enable
novel brain imaging systems.
And likewise, the technologies that exist for inspecting
semiconductor wafers in that arena may yield larger
microscopes than available today in the neuroscience world for
inspecting brain activity at a cellular scale and at the --
a level of the many of hundreds of thousands to millions
of neurons that Cory talked about.
The photonics industry also brings very powerful
technologies to bear on questions of pertinence to
neuroscience including lasers, custom fiber optics, cameras,
all of which may -- when harnessed appropriately may
allow us to visualize facets of brain activity that
we have never imagined even existed before.
In military defense, there are digital imaging technologies
and surveillance algorithms that may help us track and analyze
the movements and behaviors of small model organisms
that are widely used in brain research.
Adaptive optics, computational optic methods of seeing through
turbid media, may help us create imaging tools allowing
us to look deeper into the brains of living animals than
we've ever done before.
Robotics offers methods of mechanization and automation
for handling model species that we use.
And of course, in computation and information technology,
there are statistical learning methods that today might
be used to track patterns of consumer behavior,
but these same machine learning algorithms might yield new means
of identifying large scale patterns of brain activity
in helping us understand how these patterns might go awry
in brain disease and brain disorders.
So part of the opportunity here is to capture and combine
all these constituent technologies where possible,
but to achieve these gains and others that we have
not even realized.
It will be important for the technological communities,
the engineering communities to work very closely with
the neuroscience community in a way that has scarcely
happened in the past.
But I think we really need to do this.
The challenges are so great and important that we must
collectively rise to this challenge and I hope that a main
facet of the BRAIN Initiative will -- that we'll see new
levels of cooperation between different scientific disciplines
and different fields to a degree that neuroscience research
at least has never experienced before but
that has characterized previous presidential
science initiatives.
And if we can achieve this very tight level of cooperation
between the neuroscience community,
other science communities, and the engineering communities,
then I think this will be very important towards making
the BRAIN Initiative a wonderful success.
Paul Alivisatos: Great.
Thank you very much.
So what I've heard from these two comments so far is that
on the one hand, we have a tremendous -- we have a gap.
There's still a lot to be done at the molecular level and at
the level of the science of individual neurons and there's
still a lot to be done at the level of very large scale
imaging, but nonetheless, there's this gap in between
where the precise imaging in the sort of neural circuit,
million neuron kind of range is really -- that's where there's
a very special new gap that's opened up.
And at the same time, other disciplines have made these
tremendous advances that could be harnessed for that purpose in
terms of our ability to have new materials and new concepts
in electronics and optics, new kinds of, you know,
highly parallel data stream handling,
advanced computation -- all those things.
They appear -- so there appears to be this kind of wonderful
convergence that's going to really create an opportunity for
us and I think one of the issues we're going to be struggling a
little bit with and we're going to talk about it a little
in both -- in this panel and the next one is how are
we going to get from here to there because we have these
very diverse (laughs) activities that have to come together.
And so my first question to you is -- and meanwhile I think
if you're writing questions down, they can potentially
be filtered up to me here because otherwise I'm just
going to be asking the questions, which would
be no good.
So we have these two things and we need to bring them together
and it's going to be, you know, a complicated thing to do.
And so for each of you, you must have considered this quite a bit
in the past couple of years as this initiative has started
to gain traction.
What do you think are some new models or mechanisms for
collaboration that need to be developed around
the BRAIN Initiative in order for it to be successful?
Do you have some thoughts about that aspect of it?
Cornelia Bargmann: So I'll start.
I -- this morning, I was at an announcement of the first grants
that the National Institutes of Health is funding through
the BRAIN Initiative.
And one of the things that's really notable about those
grants and that's quite different from what NIH usually
does is that most of them represented collaborations
between scientists who are neuroscientists and scientists
from some other area.
So there would be a chemist, a physicist, a material scientist,
a nanoscientist as part of a collaborative team.
And I think even expressing the importance of technology
as an important step in itself has been something that
hasn't necessarily been a scientific emphasis,
and once that idea was expressed,
it turned out that there was a hunger and good ideas
for how to develop that.
And I think, you know, the ideas that emerged in my opinion were
more interesting than what we had been thinking might have
happened when we put together some of the ideas for the
future, which is as it should be when many people come up with --
you filter out the very best ideas from many people.
The second thing is I think that this meeting
is really important.
I think one of the things that has not been easy to do until
now has been to get together the leaders of different kinds
of organizations -- that my extremely limited experience
of the government has been that the NIH is very good
at interacting with the NIH.
(laughter)
And -- but that it's harder to bring in people from
outside the government.
It's harder to bring in the foundations.
And yet many of the most -- many of the newest ideas are emerging
in areas outside of the sort of conventional organizations
and I think having something where the BRAIN Initiative
has an identity, where people can know where to turn,
where they can know where meetings are,
where they can start to meet people from very different
places, where the intels and the Facebooks are represented
in the room and not just the academics, is going
to be really important for that next stage of development.
Paul Alivisatos: Mark, do you have some --
Mark Schnitzer: Yeah, I would build on that.
I mean, this morning I was at a panel for the National Photonics
Initiative which brought together companies that until
this year might not have thought of themselves
as having offerings for neuroscience research,
and I think that's going to be really emblematic as we try
to bridge the culture divide between the neuroscience
research community and other communities.
I think that neuroscientists will be -- are very pleased to
find out that people have tried to address many
of the challenges we face but in other contexts.
And learning what those other technologies are and seeing
what might be available to try to solve some of the issues
we face in neuroscience will be very rewarding.
At the same time, physical scientists,
computational scientists, and members of the engineering
community may already have some very exciting solutions and
technologies that they might not have considered offer utility
for neuroscience research.
And so being able to bridge these two communities and
explore what they might offer each other and get them working
together in a cooperative fashion I think points to very
some exciting times ahead.
Paul Alivisatos: Okay, very good.
Yeah.
I think that's -- it's very interesting, you know,
when you've mentioned that the new NIH-funded activities have
brought people together across the disciplines
into working groups.
And there's a certain level at which that's happening and I
think that's very exciting and once you start to find that
people are doing that, then they gain competitive edge
(laughs) a little bit by making that cooperation,
and once it's clear that that, you know, road is a good one,
then, you know, people will follow it and it becomes
a very exciting -- kind of a movement.
I guess one of the things I'm thinking about a little bit is
that there may be a need for this to happen at many different
scales, (laughs), all the way from perhaps even individual
researchers who might ultimately be trained in the
Neurotechnology area, (laughs), all the way to small groups.
But then possibly even if we really want to integrate all
these things together, we may need some larger groupings of
people to come together ultimately in order to make
all these pieces come together that are so diverse.
So to me, I can kind of see an issue of needing to think
about this at different scales of activity.
I don't know if you have any opinions about that,
but that's a thought.
I'm eagerly awaiting your questions and while we're
waiting for those, I will put out there something which,
you know, Cory, you just alluded to.
And this is an important question for discussion not
just in this panel, but I think, you know,
in all the other events that we're going to be having
here around this.
We have folks here from all these different sectors.
There are of course real medical experts.
There are front line researchers from the universities
and national labs whose expertise span a very
wide range of disciplines.
There are some private foundations that are really
breaking ground in basic and applied research in this area.
There are a lot of industry leaders here who can help
create a new economic sector essentially.
There are patient advocacy groups.
There's a huge range of government agencies here
(laughs) that are all participating in this.
And when I look at that, I have to say,
I see emerging something that's very different than other
science initiatives that we've seen previously, (laughs).
It looks a little bit different.
And we're, I think, searching around for a model of what an --
you know, this -- the BRAIN Initiative could turn out to be
a model really for what a new type of science initiative is
that integrates beyond the government activities and brings
all these pieces together in a certain way.
So maybe you have some thoughts on how we could do that because
it's going to be more than just a conference like this probably
to make it happen, right?
Any thoughts on that?
I don't want to put you on the spot,
but I think we need to be thinking about that.
Mark Schnitzer: Well, I think you're right in saying that
this is happening at different scales.
Even within individual universities,
we're seeing students from diverse fields becoming
interested in neuroscience because of the BRAIN Initiative,
joining research groups they might not have otherwise.
At the same time at a broader scale,
we're seeing organizations, research umbrella groups,
thinking about reaching out to different communities,
forming cooperative agreements consortia and so forth.
So I think this kind of collaborative,
cooperative spirit that we will absolutely need for the BRAIN
Initiative is indeed as you pointed out happening
at the level of individuals, but also
happening at the level of organizations.
Paul Alivisatos: Okay.
I've received some interesting questions.
Thank you.
And I'm going to start with one that I'm partial to.
So --
(laughter)
-- I get to choose, right?
I mean, that's how this thing kind of works.
I -- that's why some people don't always like this method
because it's -- you know, the moderator can kind
of bias things.
But what can we do institutionally to foster the
development of theories that bridge the gap between
neurons and behavior?
And I think this is a very core question.
It comes from Gary Marcus from NYU.
Thank you for asking this important question.
And I think that it's really at the core
of the initiative at some level.
I mean, how are we going to actually improve
understanding and not just provide lots of observations?
Cornelia Bargmann: I -- if I can comment,
I think that theory has been very important in biology
at a point that there was sufficient data,
that there was a real conversation between
the theorists and the experimentalists about not
just how something might work in principle,
but how something worked in real life.
What predictions did this kind of a model or a theory make?
How did that manifest itself in the next round of experiments?
Were those predictions met?
Does it have to be modified?
And there is a real hunger for theory in neuroscience,
and when you see the occasional theories that we do have,
like the dopamine reward prediction error theory which
has ways of thinking about everything from the most basic
learning of motor skills to models of drug addictions
in humans, you see what -- how powerful those notions are
when we can develop them.
And I would say that the trick is going to be really putting
those people together.
You know, the ideal would be that every BRAIN Initiative
neuroscientist might have a theoretical partner or --
in some of these and that conversely,
every theorist would be really grappling with what experimental
data really looks like instead of what you wish it looked like.
(laughter)
Paul Alivisatos: Yeah.
You know, that's actually --
Cornelia Bargmann: I'm sorry.
Paul Alivisatos: -- that's great.
You know, there is a very famous -- I guess it's a joke
from Ernest Rutherford, discoverer of the nucleus.
And at one point, he said there are only two fields of science,
physics and stamp collecting.
(laughter)
And I believe he meant to be pejorative about the stamp
collecting, but in fact, I do think that at some very
fundamental level, there is a period required of observation
that helps provide the lay of the land,
the map of what's happening and then, you know,
theories can emerge.
But that's not entirely satisfying and I think the
question does appear on this --
Cornelia Bargmann: Yeah.
Paul Alivisatos: -- point of -- you know,
we need to -- as you were just saying,
we need to actually build that into the initiative,
that it's an expectation that people should be pushing
to have theories tested and not just, you know,
performing the observation in isolation.
Mark, you look like you want to jump in on that.
Mark Schnitzer: Yeah, I think the neuroscience community
is very receptive to this.
In neuroscience, we have one of the most successful examples
of a theoretical contribution, namely the three of nerve
conduction from Hodgkin-Huxley, and this is something that
every bee-gee-tee student in neuroscience learns.
And then more recently in the 1980s,
there was a substantial influx of ideas from theoretical
physics as a neural network theory was developed and also
from theoretical engineering.
So I think the neuroscience community already recognizes
the importance of theory.
This was an important facet of the NIH Brain Report
that we wrote.
So I think that the ground has been laid for a very strong
theoretical contribution, and as Cory points out,
I think the close interactions between the theorists
and the experimentalists will be key.
Theory is going to have very important roles for prompting
new questions that experimentalists might not have
thought of on their own, but they can address with the state
of the art tools and technologies that are emerging.
And as also was stressed, we can't just acquire
large data sets.
We have to have conceptual advance that goes along with
that and theorists will have an integral role in helping
us understand and interpret the state of the art data
sets that we aim to acquire.
Paul Alivisatos: Very good.
Thank you.
So now we have a pair of questions that are a little
bit more focused in, but very important.
The first one is DARPA has made breakthroughs in human
computer interaction from remote control of cursors
and computers to prosthetics.
How will the BRAIN Initiative leverage that research?
So perhaps either of you has a feeling for that question.
Cornelia Bargmann: I'm actually looking at a person in the room
who was involved in exactly that work, John Donaghy.
Paul Alivisatos: (laughs)
Cornelia Bargmann: And I would -- you know,
I think that the -- there -- the -- one of the advantages
of the BRAIN Initiative as it's developed has been that
different groups have started to emphasize -- have started out
with an emphasis on what they do well, that DARPA, for example,
has already started funding initiatives,
including initiatives based on deep brain stimulation
as Daria was telling you about, initiatives based on trying
to do memory restoration, that really plays off of their
particular strength and interest in the more device-oriented part
of solving real life brain problems and -- but, you know,
Mark Schnitzer: You know, I think one of the things that,
many of those things have been built on a foundation of science
that was done at a basic science level so one of them
does not replace each other.
They really complement each other.
Paul Alivisatos: Indeed.
as a community, we're appreciating more and more is
that diseases that might have seemed disparate in fact have
some common elements and by building a platform of knowledge
and a platform of technology through the Brain Initiative we
can try to make advances across diverse areas or areas that
initially seemed diverse.
And so by pushing forward our basic knowledge but also our
basic technological capabilities there will be future
opportunities for specific projects to develop very
exciting technologies that will bring forth technologies that
may even impact human health that we never would have thought
possible without the groundwork that the Brain Initiative lays.
Paul Alivisatos: So, this next question I think is very
connected because, you know, the previous one was
human computer interaction: how do we exploit it?
This one is related but I think it takes us to an interesting
place because it also deals with certain aspects of the
interventions that are involved potentially in this.
How do you think the Brain Initiative should work to
advance understanding of the human brain non-invasively
at the system level?
Female Speaker: So that is an absolutely key transition that
has to happen between animal and human neuroscience and I would
say that one of the areas of the new NIH grants actually that
I found most appealing when looking at the new funding
opportunities is the number of people who are thinking
of completely new ways of interacting with human brains
non-invasively, of using methods like Pet and MRI in a mobile
platform instead of shutting you inside a box,
of trying to think of completely new ways of interacting with
brain modulation through magnetic fields or through
focused ultrasound and I think that, again,
this is an area where the physical sciences can combine
with what is being learned in biology to advance things.
Which of these things will work?
Who knows?
But if 20 percent of them work, if just a couple of them work
they could really change what we can do in terms of examining
the human brain in natural conditions at speed.
Mark Schnitzer: I would bring two points in this context.
I think that there are possibilities for new physical
imaging and perturbation modalities that have only
just begun to be considered.
There's a history in physics and technology of effects that once
seemed esoteric eventually finding their way into standard
fare and so new modalities that might be based on effects such
as magneto optics and other fairly nuanced physical effects
offer some interesting promise and as Cori said only a subset
of these will eventually pan out but, obviously,
creative thinking regarding new physical effects,
new ways of interrogating the human brain non-invasively
will be very important.
Secondly, this is a key area where I think that coordination
between researchers looking at animal brains and researchers
working in the clinic with human brains can really
pay some dividends.
So, for example, there are certain signals that we can
record non-invasively in the human brain and in animals we
could record those same signals but also look at the underlying
cellular basis for these signals and get a deeper mechanistic
understanding of what might be causing the signals that we can
record non-invasively in the clinic and that also will deepen
our understanding of what we can measure in the clinic
and, hopefully, point us toward new diagnostics
and new therapeutics.
Paul Alivisatos: Okay, Professor Bargmann
and Professor Schnitzer.
I want to thank you very much for helping this panel to start
the discussion about the science and technology side
and we're now going to switch over to your colleagues.
(applause)
So while our two new panelists are coming up I'll start
just by saying that the Brain Initiative, of course,
really is -- it's exciting science and it's going to be
also I think really wonderful, beautiful science.
But the work itself is really, it's really ultimately geared
toward helping people in society and we really are going to need
to organize ourselves carefully to make sure that we do end
up having the kinds of impacts that we're looking for,
that we all hope for.
We know that there are instances really of traumatic brain injury
and posttraumatic stress disorder, to just name two,
that are really, really devastating in our society and
that are really affecting huge numbers of people and their
families and so, in this panel, we're really going to be
exploring these aspects of the impacts on our society and we're
very, very fortunate to have a wonderful panel here.
We have Jeff Manley who's Chief of Neurosurgery at San Francisco
General Hospital and Professor of Neurosurgery at the
University of California San Francisco and Kerry Ressler
who's Professor of Psychiatry and Behavioral Sciences
at the Yerkes Research Center
at Emory University and Co-Director
of the Grady Trauma Project.
Now Professor Manley, you're a trauma neurosurgeon.
You have clinical interests in brain injury,
spinal cord injury, neuro-critical care.
Your work is on the front line of clinical research
at SF General and at UCSF.
You have remarkably wide-ranging interests when I looked up what
you were working on, even though we're practically neighbors
living both in East Bay and all that, you know.
Scaps exist (laughs) so but your work reflects an astonishing
range of research interests all the way from really molecular
aspects of brain injury to the clinical care
of head trauma patients.
So please give us your initial thoughts on this.
Professor Manley: Sure.
Well, I'm honored to have been invited today to speak
on behalf of my co-investigators and really
the TBI community at large.
Traumatic brain injury and concussion are really no longer
the silent epidemic that we referred to 10 years ago.
Traumatic brain injury's now known as the signature injury
of the wars in Iraq and Afghanistan.
There is growing awareness of concussions in a variety of
sports and we now know that it's really more than just an event.
It's really a process that, in some individuals,
can lead to lifelong disability.
However, military and sports TBI are really only the tip
of the iceberg with traumatic brain injury.
Traumatic brain injury happens all around us.
There's at least 2.5 million people in the community every
year that sustain a traumatic brain injury and go to a
hospital to seek help for this and there's probably at least
another two to 3,000,000 folks that are never even seen
by the medical community.
So we really do have an epidemic of traumatic brain injury
and this has been with us forever.
It's just now we're becoming progressively aware of this.
We have millions of people that are permanently
disabled from traumatic brain injury.
The cost estimates are in excess of 70 billion dollars a year.
Unfortunately, what we know about traumatic brain injury
is probably 40 to 50 years behind what we know about
things such as cancer and cardiovascular disease.
TBI is one of the most complex injuries in the most complex
organ in the body.
We just heard about all of these very complicated integrated
circuits and so on and then we lay upon this a very,
very complex injury and it's no wonder that this is a very,
very challenging problem and this problem is so complex that
not one investigator, one institution or one company
or one agency is going to solve this problem.
We really need everybody coming together to work together,
which I think is what is so exciting about this room is
we see all of the stakeholders sitting here today that
could really come together to try to solve this problem.
Our recent -- and I liked your quote there.
I used to be a theorist and now I'm a stamp collector...
(laughter)
But I have really cool tools these days.
Paul Alivisatos: Stamps are beautiful.
Professor Manley: So, you know, our recent efforts with track
TBI and the new TED initiative I think demonstrate the potential
of these robust private/public partnerships to be able
to address this in a multidisciplinary fashion.
When I look back over the last year in our work with companies
such as General Electric and philanthropic organizations such
as One Mind I see people coming together across multiple
disciplines really with funding from both the NIH and from
the DOD to be able to address this problem and I think
we're starting to make a little bit of progress.
So as we've just heard from Corey and others there are lots
of very, very exciting things going on in the Brain
Initiative: how groups of neurons speak to one another,
how they work in large, complex circuits and how we can start
to manipulate this, whether it's through devices
or whether we can do this with opto genetics.
However, I think that we have to look at our field
and is the clinical realm ready for this?
So, you're right.
I have a broad training background.
I'm a product of a medical scientist training program
having done a basic PhD in neuroscience and going
on and training as a neurosurgeon and so, you know,
my role is to really try to stand in the middle of this and
when I stand in the middle and I look at what's happening from
the basic science aspect and then I see what's happening
in the clinical realm we've got a lot of work
to do in the clinical realm to really get ready for this.
So, for example, today in traumatic brain injury we take
this complicated injury in this complicated organ and we use a
classification system that was developed 40 years ago and we
call traumatic brain injury mild, moderate or severe, okay.
Can you imagine us trying to come up with a treatment for
cancer calling that mild, moderate and severe?
Not a chance, right?
So there's a reason why we're not making a lot of progress.
Concussion: we have 42 definitions of concussion.
That means that nobody knows.
We've got to have more objective tools.
We've got to have the kind of things that are coming out of
the Brain Initiative, whether it's an imaging technique or
it's some sort of non-invasive brain function monitor to be
able to objectively get past all of these symptoms to really try
to come up with an objective way of looking at that.
So, as we look forward, I really think one of the solutions,
as was really advocated by the National Academy of Sciences
a couple of years ago, is a precision medicine approach.
What do I mean by a precision medicine approach?
We need to embrace the complexity of TBI and we need to
understand that there are things happening at the genetic level.
There's proteomic change.
There's changes in the imaging.
There's changes in the clinical features and, importantly,
we can't just use a simple disability measure to look
at traumatic brain injury.
We have to look at things like memory and learning and borrow
from the basic science community and translate that to where
we're really comparing apples to apples as we try to move what's
happening from the rodents and the other types of animal models
into human biology.
I really think that in order to do this and to build these
multi-scale models -- we've heard this before --
it's going to really require a lot of technology.
The idea of being able to integrate gene with a voxel
image with an outcome measure doesn't currently exist and I am
sure that there are companies that are in the room today that
have the kind of technology that have been used in other areas
that can be repurposed to help us to achieve this goal.
I think the brain injuries and neuroscience
in general really is the final frontier of medicine.
We can make progress but this is going to require
concerted effort.
This isn't just a one or two-year grant proposal.
This isn't a five-year grant proposal.
We are going to need continued and sustained funding.
This is a big problem and nobody wants to hear this.
We're not going to solve this next year.
This is something that we've got to get behind and have
a multi-year sustained commitment in order
to be able to make a difference.
I do believe that with vision, sustained commitment from
multiple partners in a multidisciplinary fashion and,
most importantly, a word that we've heard already and I'll
say it again: collaboration, collaboration, collaboration,
we can make a difference for our citizens,
our soldiers and our athletes with traumatic brain injury.
Think you.
Paul Alivisatos: Thank you.
Now I do want to ask that if you have questions -- there were a
lot of ideas there, signal please to the folks with the
cards and start writing them down now so we can be ready
momentarily for starting to get them to come in.
Professor Ressler, you have focused on the molecular
and cellular mechanisms of fear learning and the process
of extinction of fear in mouse models to improve our
understanding of and advance treatments for fear-based
disorders such as PTSD and traumatic brain injury.
We'd love to hear from you.
Professor Ressler: Thanks so much, Paul it's really
an honor to be here.
The World Health Organization has reported that mental
illnesses are the leading causes of disability worldwide
at a cost of tens of billions in the US
and trillions worldwide.
Among both our military and our at risk civilian populations
PTSD is among the most prevalent and debilitating of the anxiety
and fear disorders.
About seven to eight percent of the population will
develop PTSD at some point and that's much higher
in the traumatized risk population.
Over five million adults have PTSD during any given year.
Yet, this is only a small portion of those who have gone
through significant trauma on the battlefield,
as well as in our inner cities and other high-risk areas.
Furthermore, women are twice as likely to develop PTSD with
about 10 percent developing it at some point in their lifetime.
The symptoms of PTSD most notably develop in the early
aftermath of a trauma: the weeks to months following the trauma.
They can last for years to decades to a lifetime.
They include overwhelming fear, intrusive memories,
avoidance of trauma reminders, hyper-arousal among others,
including one of the most common causes of depression.
These symptoms can be overwhelming to the victims.
They're often referred to as an emotional black hole
that you can't escape from: these memories.
Those with severe PTSD often generalize these symptoms.
They can have difficulty holding jobs, keeping relationships.
They can become paranoid and have erratic behavior all from
this underlying, extreme fear based on past memories.
It's a severe problem in our veterans who have given their
life for our country and it is an under recognized,
near epidemic proportions in our inner cities where violence,
drugs and fear are the rule.
At a time where there's so much promise in our nation and
the world it's shameful that a disorder of fear prevents
progress for so many.
But science offers hope.
PTSD offers an ideal opportunity to study environmental and
biological factors that result in the development
of pathological trauma responses because we know
when it starts.
It's the only psychiatric disorder where we can say
we know when it starts.
It starts at the time of the trauma.
It may be amenable to interventions initiated
shortly after the trauma to prevent its development.
New, rationally designed treatments that derive from
basic neuroscience and preclinical animal and human
studies are currently under investigation worldwide.
Remarkably, the same brain regions, the amygdala,
the hippocampus, the insula, to name a few,
are involved in fear processing from mice all the way to humans.
Therefore, PTSD and other fear disorders may be among the most
tractable targets in psychiatry because we understand a lot
of the circuitry already.
We are now beginning to functionally dissect,
using the kind of tools that have been talked about: opto
genetics, engineered dreads and others to dissect specific cell
pathways within sub-regions of the amygdala that can
specifically turn on the fear reflex or turn off the fear
reflex in a rational, designed way.
They can regulate this fight or flight response.
Further understanding of the molecular/cellular and circuit
mechanisms underlying fear will have huge implications for the
millions of people suffering from PTSD and other fear
and anxiety disorders but we need your help.
The Framingham Heart Study, started in the 1940s,
marked a watershed event in utilizing large,
cross-sectional, collaborative and perspective research
to identify risk factors for cardiovascular disease,
changing the prevalence treatment and prevention
strategies for heart attacks, strokes and related illnesses
in the meantime.
It is time that we do the same thing for mental health.
As a beginning, several ongoing initiatives between the NIH
and the military, including the Army Stars Project,
Strong Star and others are beginning to provide some
similar large scientific cohorts for mental disorders.
But the field needs support from private partnerships as well
since this cannot be done by the government alone.
For example, the Human Genome Project led to the more recent
Psychiatric Genomics Consortium which has led to huge success
with very large collaborations of hundreds of thousands
of samples leading to new discoveries in schizophrenia
and autism which are leading to understanding at a molecular
level of entirely new approaches to these
very debilitating disorders.
We need to do the same for other disorders of the brain.
Up to forty percent of PTSD, much of the difference between
risk versus resilience after a trauma,
is genetically determined.
Consortia are under way to uncover the genomic
architecture of PTSD through similar
large-scale collaborative studies.
By identifying its genetic pathways and integrating that
knowledge with the neuro circuits that we're starting
to understand related to fear, we can make great progress.
Every day promising advances are being translated from basic
science to the clinic, including methods to interfere with fear
development after a trauma and prevent PTSD from forming
initially, as well as techniques to augment therapy by
normalizing the fearful emotional memories.
Invasive treatments that affect disrupted emotional circuits
such as trans-cranial magnetic stimulation and deep brain
stimulation are borrowed from neurosurgical interventions
and attempt to regulate the known brain target
discovered from neuroscience.
Other approaches include drugs that are given at the time of
specific learning events to enhance or disrupt the motion
of learning with talk therapy derived from neuroscience
of learning, memory and brain plasticity.
Neuroimaging shows us the common brain regions are targeted
with both biological treatments and emotional learning.
By understanding the roles of specific molecules and cells,
circuits and pathways underlying fear and emotion,
we'll be able to target both the prevention of PTSD at the early
hours on the battlefield or in the emergency department,
as well is to utilize new, targeted and powerful approaches
to treatment and recovery.
But to do this the field needs your help and we need a greater
understanding of the brain.
Thanks.
Paul Alivisatos: Thank you very much.
So I think I detect a common theme there which is that,
in both areas, you have already taken steps of using some
of the most recent advances in the, you know,
molecular science and in science that's taking place at the level
of neurons and so on: that you've been integrating that
already into your programs.
And I think that's very exciting and I'm wondering how you
think that's going to work going forward.
We talked earlier a little bit with the previous group about
the ways to bring people together and that there might
be ways to do that at different scales: small scales
and larger scales, education of individuals and so on.
You mentioned the Human Genome Project, Kerry,
which I think is a fascinating case.
I mean, there, obviously, things happened at a large-scale.
(inaudible) is here from, you know,
one of the people who helped to guide us to that initiative
and I know that our lab played an important role
in it at one time.
But my impression is that that project,
although people were very interested in the implications
from the very beginning, it took a while for that to kind of --
and so the question is can we make it happen a little bit
faster this time by integration early?
So, I wonder what your thoughts are on that?
What kind of practical things can we do to make
it happen more seamlessly?
Professor Manley: Sure, I think this is going to require
collaboration and team science.
We need to understand that we're looking at a human that's been
injured and we had previously been very -- we'd been
reductionist about this.
We had people that were doing MR imaging and we had people that
were looking at the genetics and what we've done with some
of these recent public/private partnerships that we've put
together is that we've brought together folks from the entire
spectrum, whether they were interested in the acute
phenomena, whether they were imagers,
whether they were outcomes specialists and we've all
come together to focus on the patient as the goal
in a multidisciplinary way and, more importantly,
some of the work that we're doing with some of our corporate
partners I think is very, very important because, ultimately,
at the end of the day, we need to commercialize what we're
doing to get this to the patient's bedside
as quickly as possible.
And so when I look at, say for example,
our collaboration with GE, the things that we're doing today
I think will get to Casper, Wyoming quicker than they will
at the research centers that are doing this because we're not
waiting to get an answer.
We're actually getting the answers together and by getting
these together they're being able to be disseminated
and distributed out into the public much quicker.
We want to accelerate research.
I take care of patients on the front line.
I have families asking me every day,
"will my kid be able to graduate from high school?"
"Will my husband ever go back to work?"
And I don't have those answers.
So I was joking earlier.
We are doing a Framingham style study of traumatic brain injury.
We're collecting the stamps and we're trying to understand
what this looks like.
All I want right now is to move past mild,
moderate and severe for concussion.
I want to be able to sit there and tell a family,
"here's the probability that you'll go back to work."
I think it starts with diagnosis and, from diagnosis,
then we'll get more targeted therapies and as we're working
with our folks and all the amazing things that are
happening in the Brain Initiative this will then
filter into the work that we're doing but it requires
a lot of communication and collaboration.
We don't need to wait.
Otherwise none of us will be here by the time we come up with
treatments for something that people need right now today.
Professor Ressler: Just two brief thoughts: one,
I think related to the points that were discussed earlier with
how and what sort of non-invasive tools can we use?
We're going to need biomarkers, whether they're blood-based
biomarkers or whether they're neural imaging biomarkers that
will give us intermediate diagnostic measures beyond our
clinical observations and then we need to find ways to build
on the enormous success of molecular genomics and human
genetics and how do we take the great engineering tools
of neuroscience currently and bring genomics and genetics
and epigenetics to that to understand how every neuron
is really its own factory, working with
this epigenetic system.
Paul Alivisatos: Thank you.
So here's a question from the audience and this one comes from
Amy Nutt from the "Washington Post."
In reference to recent
research out of Northwestern how far away are we from being able
to image brains of trauma victims immediately after
the event to determine who is liable for PTSD?
Professor Ressler: Well, PTSD -- if I thought TBI was going
to be -- I'm sure both are (inaudible)
Paul Alivisatos: People want to know.
Professor Ressler: So there are techniques that Jeff can say
more about than I can whether it's DTI or DKI and some other
methods that are very sensitive to white matter,
slight disruptions that we're looking at.
And as Jeff and I were talking about beforehand,
it's increasingly looked at with whether it's neuronal disruption
or inflammation or other sorts of measures: that physical
trauma and emotional trauma seem to do many similar things
on the brain.
So how quickly will we be able with a brain image?
I don't think at a structural imaging level
we will be able to.
It's possible that with functional imaging,
whether it's resting state, which is very easy to do
anywhere quickly or with other approaches as we understand more
the bio-informatics which are extraordinarily complex but
simply the resting state: what the brain is doing alone while
lying in a scanner has an enormous amount of information
that we've only begun to tap bio-informatically in the field
and back and that can tell us an awful lot.
So I think there's hope.
Paul Alivisatos: I guess also we're obliged a little bit
to come back to the question of Gary Marcus from earlier that
if we don't have a kind of theory for understanding how
these behaviors arise, then it's going to be difficult
to be very predictive about things: perhaps,
correlational and observational at first but, you know,
we'll evolve in that respect.
Here's a second question from the audience.
"What are examples of successes from recent advances in cellular
neurobiology that have already translated
to meaningful therapies?
What could we learn from these to apply to future advances,"
and the question is from Victor Krauthammer from the FDA.
You can understand why they would be wanting
to answer that question.
Professor Manley: Well, I wish we had a therapy.
Two Saturdays ago we announced the failed trial for
progesterone, which was based upon 17 years of work with 200
positive papers in a variety of pre-clinical models and, yet,
this didn't translate into the clinical arena.
So I think that what we should recognize from that,
and I'm looking forward to the opportunity of working with
the FDA with this new TBI In Points development initiative
which is really trying to take us, you know, again,
we're talking about how to work with companies.
We also need to be working with the FDA to understand this: that
the kind of tools we've used to stratify patients for
clinical trials and the way that we've look at the outcome:
we have to throw away.
This was our 32nd or 33rd failed trial.
This is just not going to work anymore and we've got
to do a better job.
So what I would say to our FDA colleagues is that we need
to look -- you know, this is a very complicated problem.
Back to the question of the "Washington Post,"
everybody's looking for that one tool but there's
not one tool.
If I had chest pain this afternoon and I then
go to a local hospital here is it because of what I ate
for lunch or is it because I'm stressed out because
I'm in front of all these people?
You know, they're not going to just say, "well,
your chest pain is mild, moderate or severe."
They're going to run a bunch of different tests.
So this idea that one imaging tool or that one biomarker or
that one EEG is going to help us to sort of stratify these
patients: it doesn't work with the heart and the heart
is admittedly a much more simple organ than the brain.
I think this idea of sort of the one-shot -- so we've got
to basically -- I hate to say this but we have to just stop.
We have to blow the whole thing up and go back to square one
and say, "okay, what do we know, what do we don't know?"
We don't know a lot but where are we going to start and we
need to look back to our basic science community and look at
things like memory and learning tests and look at behavioral
assays and really try to replicate and translate this
to get us across what is this huge valley of death
in things like traumatic brain injury and many
of the mental health diseases that we try to study.
Professor Ressler: I would -- I'm hopeful that PTSD is more
hopeful than TBI at this point and I think that's because
I think PTSD at large is many, many things and one thing we're
clearly understanding and one thing I like to say
to my students is about half of the genes in the genome
are relatively specific to the brain and, yet, we have,
in mental health, maybe about eight clusters of disorders,
as opposed to literally hundreds to thousands
of medical disorders.
Clearly, we're lumping things together that are discreet
disorders in the genomic realm.
That said, I think there's components of PTSD that really
do offer low hanging fruit.
I think psychiatry and mental health disorders are going
to be a very broad range of things.
Some things are going to be like cancer and it's going to take
decades or centuries to get them all but I think there may
be some things that are solvable and from path love
to Eric Kandel we've studied, as a civilization,
learning and memory for over 100 years and a lot of progress has
been made and neural plasticity and learning and memory
have been some of the areas of the most progress
in the last 20 years.
And there are a number of study drugs that are now being
looked at in humans and have had a number of small,
positive trials that were based in mouse and rat studies,
specifically understanding of things like
MDA receptor regulation.
There's new things based on BD and F regulation: other sorts
of channels involved in the learning and memory plasticity
process and a lot of epigenetic regulators that are also being
looked at that really do offer hope and they may not solve the
broad PTSD that is chronic and has become depression and has
become substance abuse and multiple things but we do think
that an animal model of fear learning is a good model
of human fear learning and there certain components
of this that are quite tractable I think.
Paul Alivisatos: Very interesting, okay.
I'm going to take just a flyer for a moment here and describe
something that I think relates to this indirectly so bear
with me momentarily.
But last Friday I was with a group of other scientists
from around California.
We visited the folks at IBM: Demen Ramota is sitting here
and at that group there was some astonishing work
in the synapse project where they built circuits
that are neuromorphic.
They don't really look like brains exactly (laughs) but
they're inspired by brains and for those of you who haven't had
a chance to see that work, published recently
in "Science Magazine," that group has taken this
neuromorphic computing and machine learning
idea and they've been able to perform
some image recognition computations with better than
consuming power that's only maybe one 1000th or less of what
would be consumed if we had a conventional computer doing
it and also with some very high speed and accuracy
and so it's fascinating.
But one thing that just made me think of what you're talking
about is, of course, their circuits will sometimes
have broken pieces...
(laughter)
And pieces will kind of break in the middle and they have these
algorithms that will kind of learn to take advantage
of the parallelism and go around and, essentially,
create plasticity in an artificial system
and it seems like, from those kinds of experiences,
maybe we could learn things about -- we know that, you know,
the brain can do similar kinds of things and we'd like to
understand how that really works and so it just feels like that's
an area where, you know, we really need to have some new
discovery and perhaps you have some thoughts on that.
Professor Manley: Yeah, well, and again,
I think we heard Corey talking about perturbation of a system.
Well, when you injure your brain you perturb the system and
imagine the power of looking at the Connectome of an injured
brain versus the Connectome Project that's going on now:
very, very powerful.
I think that there actually are a lot of opportunities.
When brain injured patients come to us and they can't speak and,
yet, a year later they speak that's plasticity and repair
happening right in front of you.
And so with some of these emerging techniques with,
for example, resting state FMRI and some of these structure
function ways of looking at the brain I think we're going
to get a tremendous insight.
I don't mean to come off by saying that, you know,
we're really lost here.
I think the first step to getting someplace is to realize
that you've got an issue, to address it and to move forward.
I think that there are many, many things.
I mean, just some of the MR work that we're seeing
that's identifying patients that were, you know,
currently we use CT scans when you come into
an emergency department.
I think within the next couple of years the work that
we're doing now: we'll have you looking at MRIs.
That's going to be an immediate advance and help for people that
have traumatic brain injuries.
So I think there's a lot of opportunities but, again,
as I said earlier, we really have to do this working
together as a collaborative group and I'm very,
very encouraged with the spirit of collaboration that
I've seen here and with some of these emerging,
multidisciplinary sort of big team science efforts.
Professor Ressler: And I just hit on that too because I think
it's a beautiful way of saying it that most of our treatments
that we currently, empirically found probably aren't getting
at the underlying pathology and in the same way,
whether it's the brain simulation or whether it's
enhancing plasticity, there are lots of ways -- you can fix
something without understanding the pathology just like we had
pacemakers that were very useful long before we understood
mechanisms of arrhythmia and I think there's something
to be learned from that.
Paul Alivisatos: Thank you for that very much.
Well, I think I can say, on behalf of all the folks here,
how thankful we are to have you working on these critical
issues that affect so many people: you know,
the traumatic brain injury and posttraumatic stress disorder
and those are two very critical examples but, as we all know,
there are many examples where, you know,
the illnesses associated with the brain are so debilitating
for people in society and we all are going to try and work harder
together to make some progress on this so thank you very much.
(applause)
Meredith Drosback: Thanks once again to all of our panelists.
I think they have given us a lot to think about.
Our next speaker is Tom Khalil.
Tom Khalil is the Deputy Director for Technology and
Innovation for the White House Office of Science and Technology
Policy and Senior Advisor for Science Technology and
Innovation for the National Economic Council.
In this role, Tom serves as the senior White House staffer
charged with coordinating the government's technology
and innovation agenda.
He's been deeply involved with the Brain Initiative since its
inception and is going to share with us some details of the
private sector commitments that have been announced today.
Please welcome Tom Khalil.
(applause)
Tom Khalil: Thank you.
Good afternoon and, at the risk of sounding like
I'm at the Oscars, I have a lot of people that
I would like to thank.
(laughter)
Tom Khalil: I want to start off by acknowledging a number
of the people who worked really hard to make this event
possible and, particularly, Robbie Barbero.
Robbie and his wife had a baby boy at three AM on Sunday
and he's working all the way up to that point to make this
possible: really cute kid but I also want to thank Noemie Levi
with the Domestic Policy Council and Meredith who's been doing
a spectacular job as MC, Phil Larson, Kristin Lee, Fay Jenks,
Randy Paris with the Office of Science and Technology Policy
and also Phil Rubin who's being leading the broader White House
neuroscience initiative.
So please join me in giving them a hand.
(applause)
Tom Khalil: Well, as you know, when President Obama launched
the Brain Initiative in April of last year as one of his
administration grand challenges he issued a call to action
to encourage companies, foundations,
private research institutions, universities,
patient advocacy organizations to join with him in supporting
the goals of this effort and this is really important
because, as a number of the previous speakers have noted,
we're going to be much more likely to achieve the ambitious
goals of this initiative if we have a broad coalition
of individuals and organizations, both inside
and outside the federal government, that are
providing their ideas, their financial support
and their expertise.
And the administration has really been delighted with
the thoughtful response to this call to action that
we're announcing today.
We've had a number of commitments from companies that
have the potential to bring new tools and technologies
to neuroscience of the types that the previous speakers
were talking about.
So members of the National Photonics Initiative,
including Acumentra, Adulant, Applied Scientific
Instrumentation, Coherent, Hamamatsu, Inscopix,
Spectro Physics and ThorLab will be investing at least
30 million dollars in existing and new R&D to help
achieve the goals of the Brain Initiative and bringing
the expertise in technologies, such as imaging optics,
laser sources, automated scanning technologies
and high-resolution cameras.
GE today is launching a new brain health initiative that's
going to build on and help coordinate their activities
across not only their corporate venture capital
but their important work on open innovation,
corporate R&D and their healthcare lines of business.
Google engineers are already building tools
and infrastructure necessary to analyze
petabyte scale datasets.
That's quadrillions of bytes of information.
I'm sure next time we get together we'll be talking about
exobytes but these are data sets that are going to be generated
by the Brain Initiative and they're already working with
the Allen Institute, HHMI and several academic partners.
Glaxo Smith Kline is providing up to five million dollars
in new funding for the research community to develop innovative,
peripheral neural technologies which could help develop
treatments for chronic diseases such as asthma,
hypertension and arthritis.
Inscopix is doubling the number of grants that they are going
to award to researchers to help them image and interpret
large-scale neural activity.
Carl Zeiss Microscopy and UC Berkeley are teaming
up to invest 12 million dollars in the development of neural
technologies including the Berkeley Brain Microscopy
Innovation Center and there are number of other universities
that are making investments that are aligned with
the Brain Initiative as well.
So the University of Pittsburgh is announcing 65 million dollars
in funding for the University of Pittsburg Brain Institute.
Carnegie Mellon University will be providing 40 million over
the next five years for its Brain Hub Initiative with
support for new faculty positions, graduate
and post-doctoral fellowships and seed funding for research.
The entire University of Texas system is rallying behind this.
They've organized a multi-campus neuroscience council in response
to the Brain Initiative and have already committed 20 million
dollars for equipment, faculty recruitment and access
to its cutting edge supercomputer.
The University of Utah is committing 10 million dollars
to launch an interdisciplinary neuroscience initiative.
Boston University is launching multiple research centers
in areas such as neural imaging, systems neuroscience
and neural technologies and several foundations
are making investments that are also going to advance
the goals of the Brain Initiative.
Earlier this year the Simons Foundation announced
a 62 million dollar Simons collaboration on the global
brain which seeks to uncover patterns of neural activity
that produce cognition.
The Children's Neurobiological Solutions Foundation
is expanding their pediatric brain mapping project with
a goal of doubling the number of children that are
participating in the project from 5000 to 10,000.
The Brain and Behavior Research Foundation is increasing its
support for the most promising young scientists involved
in neurobiological research and we also have a number
of organizations that are interested in fostering
the technological innovation that is needed to achieve
the goals of the Brain Initiative.
The basic and fundamental research is great but
if we want to actually see these new tools we're going
to have to see the emergence of regional clusters.
The Pacific Northwest Neuroscience Neighborhood
will work to promote a vibrant neurotechnology cluster
in Oregon and Washington State.
The neurotechnology Architecting Network is committing to mentor
and train innovators who will design, prototype, assess,
and distribute at least a dozen technologies for
mapping and recording neural circuits.
This network aims to create a distributive neurotechnology
valley that will disseminate these tools,
both to advance fundamental understanding and to advance
clinical applications and, in addition to all these
new commitments, I want to acknowledge that three
organizations that supported the Brain Initiative from
the very beginning have made remarkable progress since
the President's announcement in April of 2013.
Consistent with its 2013 commitment to invest 60 million
dollars a year in projects and partnerships related
to the Brain Initiative in 2014 the Allen Institute
completed the Allen Mouse Brain Conductivity Atlas
and helped establish an annual conference for
large-scale brain initiatives with a Keystone Symposia.
The Howard Hughes Medical Institute invested more than 70
million dollars to support the goals of the Brain Initiative
during the last year with a focus on developing new imaging
technologies and understanding how information
is stored and processed in neural networks.
The Cobley Foundation, which played a very important role
in the early discussions about the Brain Initiative,
plans to endow two new neuroscience institutes
by the end of 2015.
Working with GE, HHMI and the Allen Institute,
the Cobley Foundation has also been supporting Neurodata
Without Borders which is getting the research community together
to work on important things like metadata standards.
So this is really, in a short period of time,
an exciting set of commitments.
So please join me in congratulating the individuals
and organizations that made them happen.
(applause)
Finally, I want to note that I hope that this is just
the beginning and that the Brain Initiative will continue
to serve as a catalyst for investments by companies,
foundations and philanthropists, private research institutions,
universities, patient groups, professional societies and
regions and Paul, I think, gave us a really important challenge
which is it's great to occasionally pull all of you
together and to see this, you know, really exciting,
multidisciplinary, multi-sector group of people but one
important question that Paul has given us is how do we sustain
these things and what is the right, you know,
level of organization from the small team to some
of the complex systems engineering projects that
Mark was talking about.
So food for thought and we're now going to have a great panel
where you'll learn the remarkable progress that
the science agencies that have been leading
the Brain Initiative have been able to pull off since
the President unveiled this in April of 2013.
So, again, thanks for coming and thanks for the remarkable
progress that you have all made in such a short period of time.
(applause)