The White House Conference on the BRAIN Initiative


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, 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. Mark Schnitzer: You know, I
think one of the things that, 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)

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