Eric Green: Well good morning everyone.
Let me start out by -of course- thanking all of you for coming to Bethesda, in some cases
travelling from far away and spending a day with us to really help us think through strategically
where we should be in this important area that we're going to be discussing, based on
experience so far with the CSER program, but really as the title implies, really thinking
about it beyond, what's next, and that's at a critical time for us to sort of get that
kind of feedback.
So as always, we appreciate people giving their time to help us think through the best
use of our resources, especially in exciting areas like this where there are many things
to do, and we need to figure out exactly the best way to do them.
It is an interesting week actually, and besides this workshop taking place this week, there
were two other things greatly on my mind.
One not so great, and in terms of the potential of what it would do to some of us and the
other I think is worth pointing out.
It's, you know, it was obviously of great concern to many of us that we might potentially
be facing another shutdown this week.
The good news that seems to be coming out of the news is that we may have averted a
shutdown because of some political maneuvering that's gone on, so hopefully we will stay
open this week after Thursday.
I would just -- people have already asked me about this, all we've really done is dodged
a bullet for now.
This -- from what I understand, what's going to happen is we will be on a continuing resolution
until December or so, and probably face the same circumstance again at that time, but
maybe -- maybe more rational heads will come into play and we'll actually get a budget
at some point.
But at least it seems we're going to be open beyond Thursday.
But Thursday, actually moving to a more positive thought, Thursday actually I think is a very
significant day for all of us and for all of the people involved in genomics.
If you're not keeping track of this, Thursday will be October 1, 2015, which will be precisely
the 25th anniversary since the launch of the human genome project.
And on the one hand, it is just an odometer moment, and it really is, it's 25 -- you know,
it's just the launch, 25 years -- on the other hand, I -- maybe it's -- maybe my advancing
age or something, I can't help but so sort of think back as somebody who got involved
in the genome project on day one and basically decided to dedicate my career to this new
field, what was then a new field.
And I've just got to say that if 25 years ago you would've come up to me and said that,
you know, within 25 years, you're going to be having major meetings to figure out exactly
how genome sequencing is going to become part of the mainstream of clinical medicine, I
would have said not a chance in 25 years, I said maybe 40 or 50.
I don't know how the rest of you feel, and various of you got involved in genomics at
various stages, but I just find it sort of breathtaking to think that we've gone in 25
years from just saying we're going to sequence the human genome, not really knowing how we
were going to actually do that, but just saying we were going to do it, to actually now operationalizing
this in a fashion that allows us to actually use this as part of medicine.
I just think that is phenomenal.
So I'm taking the odometer moment fairly seriously, because I just think it's a tribute to the
community of scientists that have made genomics such a robust discipline.
And bring us to meetings like this where we really are thinking about truly impactful
things that could come out of genomic advances with respect to how we practice medicine.
So I think in some ways the 25th anniversary is very inspirational for this workshop, and
what we're trying to accomplish today, which is why I wanted to sort of point it out to
you.
Okay, so besides those three things happening this week, let's talk about the third one,
which is today's meeting.
What I was asked to do is to just briefly orient you to what really we're asking in
terms of for the discussion where we want this to go.
I sort of thought there's three things going on in NHGRI that sort of all come together,
you're going to -- and I'm going to introduce two of them, and Teri Manolio's going to introduce
the third.
You know, one is everything we do in our extramural and intramural program, but in particularly
our extramural program is framed around our strategic plan that we published back in 2011.
So that has to be considered the origins of this program, the CSER program, were within
our genome sequencing program, which is now in the midst of a renewal and has some important
contextual things to think about with respect to the CSER program, and so I want to review
that briefly.
And then everything we're talking about here relates to genomic medicine and our growing
genomic medicine portfolio.
And so that's what Teri Manolio's going to describe.
And really where our discussion today is right in the middle of this Venn diagram, by the
intersection -- at least from a historical point of view, of these three major areas.
So let me start with the strategic plan, which we think actually is still pretty darn good,
even though it's four years old.
It introduced, as all of you I'm sure are quite familiar, this notion of organizing
our thinking around genomics and other programs that NHGRI does is to these five really overlapping
domains of activities, progressing on the left side for more basic pursuits to the right
side of far more clinical pursuits and everything in between.
The thing that for the institute that was significant in this strategic plan compared
to previous ones was the overt reference to genomic medicine as sort of an important goal
of where the institute is heading, in addition to everything it's been doing traditionally.
And in particular these two areas were ones that were we were sort of moving towards expanding
our portfolio beyond more basic genomics and inclusion of the use of genomics to understand
disease, but now embracing clinical applications as well.
So that's the context of our strategic plan.
When it came time to consider how we were going start to operationalize genome sequencing
and think about clinical applications, the obvious home for it at that time was within
our very well-known genome sequencing program, which I think from the beginning of the institute,
and really from the beginning of the genome project in some ways just represents the cutting
edge of genomic analysis.
If you sort of go through time, what our genome sequencing program has been affiliated with,
it has matured, starting with its origins in the genome project, moving to comparative
genomics and then genomic variation, such as Thousand Genomes, a program that is wrapping
up after being highly successful.
Most recently looking at cancer genomics and then at the far right end is in its most -- also
in its most recent iteration, addressing rare and common diseases, and as part of the CSER
program, clinical care.
So this has sort of been the progression over time.
In its most recent iteration, the genome sequencing program, which is -- and its phase will end
at the end of this year- consisted of four components.
The largest component associated with the three very large centers under a program that
was -- has been entitled “Large-Scale Genome Sequencing Analysis Centers.”
All of you are quite familiar with their work, but I would say the major focus of what they've
been doing in the last four years has been refining the implementation of next generation
sequencing platforms, strategically figuring out how to use prodigious amount of sequence
data that could be generated for a study in human disease.
Heavy emphasis on cancer with things like the cancer genome atlas, and also starting
to address big projects of common diseases such as Alzheimer's disease, Diabetes, and
so forth.
When we renewed the program back in 2012, we dedicated a separate program just looking
at rare diseases, and launched our centers for Mendelian Genomics, a highly successful
program that is now in the midst of being renewed.
We also had a component that tried to develop computational tools for the common researcher
if you will, basically trying to refine very sophisticated tools that specialists could
use and make them available to a broader audience of researchers.
An IC Tools program, again, a successful program that actually in many ways I think set the
stage for other similar initiatives, even at the NIH level such as the “Big Data to
Knowledge Program” or BD2K program.
And in fact those sorts of, we are not continuing IC Tools the way it is, but rather it's going
to sort of merge and synergize in a broader way with other activities going on, both at
the institute and at the NIH holistically.
And then of course the fourth component was the CSER program, which all of you are quite
familiar with and we're here to discuss.
Now follow -- and where I would sort of regard the CSER program, merging it now with the
concept of our strategic plan is firmly right there in the fourth domain of the five domain
progression, advancing the science of medicine.
That's really what it is, and to test mode, in fact, I often refer to this program as
a “test drive program”.
We were test-driving genome sequencing in the clinic and learning for the first time
what we needed to know to make this a more robust approach.
I sometimes refer to sort of “sticking our toe in the water” in terms of clinical sequencing.
This really was some of the first application NHGRI was supporting for clinical applications
of genome sequencing.
But then when it came time to renew our sequencing program, which we're in the midst of doing
now, for funding that will begin mostly next year, and then beyond.
We made a number of strategic decisions.
One was decision was to basically have the CSER program bought out formally from this,
having been successfully incubated within the Genome Sequencing program, and rather
seen it much more -- a natural home with the Genomic Medicine program, and also there is
some issues about funding years and so forth.
So it essentially has butted out from that.
The Genome Sequencing program as it is currently now going to be renewed will consist of no
longer just large scale centers, but rather the centers that are being -- they will be
large, but they're being renamed with a focus on common disease, so Centers for Common Disease
Genomics.
As I told you, the renewal of our centers for Mendelian Genomics, again, two programs,
one on common diseases, one on rare diseases.
The introduction of a new coordinating center to provide overarching coordination across
this -- these two other programs.
And then -- and these are all by the way programs we'll be announcing and funding that actually
just -- the decisions were brought to our council a week ago, and in the coming weeks,
we will be announcing exactly what the funding is going to look like in a public form.
And then two other components that are in the midst of going through the maturation
towards applications and review and funding, one related to setting up some centers to
just look at analysis and also a program to try to look at human and non-human primate
genome sequences at very high quality.
And there will be other components as well that will be coming down the pipe.
But this is the main components of what will be our renewed genome-sequencing program.
So that's what I wanted to describe to you, how the strategic plan brought us to where
we wanted to look at clinical applications, how it was incubated into fashion through
our genome sequencing program in the last reiteration, and how this now fits very nicely
into the genomic medicine portfolio that Teri is about to tell you about.
But the last thing I was asked to just briefly summarize really doesn't fit on this slide
per se because it's not just NHGRI, and all these things are just about our institute,
but rather there is sort of another dimension that I think is relevant, and it will probably
come up for discussion today.
Not that it is exactly what CSER does by any stretch of the imagination, but is certainly
going to be something of big potential influence, and we will be learning a lot from, and we
want to be thinking about at NHGRI level, how our programs would synergize with a larger
government program, not even just NIH, around precision medicine.
And a lot of attention has been paid to this since the announcement by President Obama
in the State of the Union Address on January 20, and then his formal announcement on January
30 of his desire to launch a U.S. precision medicine initiative.
I assume most of you have looked at the one thing in the scientific literature describing
the initiative that Collins and Varmus [spelled phonetically] co-authored on January 30 in
the New England Journal of Medicine.
More specifically the initiative has two major components, one around cancer genomics, which
the Cancer Institute is basically running with and run around the construction of a
U.S. national cohort.
For those of you who aren't familiar with us or want to learn more, there is a lot of
stuff that has happened over the last six or eight months, about five or six workshops.
Lots of documents written, lots of video has been recorded from these workshops, lots of
summaries and all of this is I think very nicely catalogued on this landing page at
NIH about the initiative.
I would strongly urge you to continue to look here; this is where all information will be
put forth.
Of particular interest I think for NHGRI I think certainly for the discussion today is
going to be this notion that there hopefully will be the assembly of a U.S. national research
cohort of upwards of a million people or probably more, where there'll be a lot of integration
of medical data, genomic data, and various other physiological and social data providing
a resource for probably some unprecedented studies of scope and scale, and how that might
influence what we should be doing as an institute in thinking about genomic applications of
-- into medicine, I think is certainly worthwhile -- worth our consideration.
It is significant that on September 17, so really just not even a couple weeks ago, under
that was the release of a working group report shown on the left accompanied by a lot of
-- like a press release and a lot of press attention showed on the right, where a working
group of the advisory committee to the NIH director that deliberated for about six months
put together a very detailed report of what this cohort program should look like, and
I would send you, again, to the landing page to look at that report and to see what exactly
that -- one imagines this is going to look like, and there's a lot of implementation
activities going on now, both at NIH and actually other parts of the federal government that
to try to make this thing a reality, beginning potentially in fiscal ‘16, because this
will involve new money.
It requires congress giving new money for this; hopefully that will be forthcoming at
some point, and we are assuming it will be there, and therefore are planning accordingly.
So again, I think this is worth keeping in mind as the discussion goes on as well.
So what we are asking for this program review meeting as we call it, to look critically
at what the CSER program has done, and in particular looking forward, the and beyond
part is to really go through these objectives.
These are listed at the top of your agenda, I don't need to read them, but I really would
tell you to routinely throughout the day look at them, because this is the focus of what
we're trying to get at.
And in particular, I would emphasize -- they're all important, but number three is the thing
that's going to lead to action for us, is to really think about organizationally if
we're going to have a follow on program.
Organizationally, what should it look like?
We have a little bit of a clean slate, we're hitting the reset button, we could do it a
lot of different ways, and I'm going to be asking very hard questions of staff about
exactly if we do something, how should it be structured, especially in the 2016 context,
which is very different than where we were in a 2012 context.
I assure you we are listening to you, this is not just a for-show.
I have no idea what the recommendations or what the discussion's going to be today, I
have no idea what the synthesis is going to look like.
We really are here to listen.
Not only are we going to listen to all of you, and we absolutely will be listening to
all of you.
You know, I would also point out that we have a heavy dose of our advisors here, and I was
just actually -- I was given the list of both recent former members of our council, current
members of our council, even incoming members of our council who start officially in -- at
the February meeting coming up.
Just so you know who they are, Eric Boerwinkle, Carlos Bustamante , who I think's going to
be on the phone line, Kardin [spelled phonetically], Rex Chisholm, Jim Evans, Gail Henderson, Chanita
Hughes Halbert, Amy McGuire [spelled phonetically], Howard McCloud [spelled phonetically], Rob
Bob [spelled phonetically], Nussbaum Ohno-Machado, and Dan Roden.
So you can see we stack the deck heavily by our advisors, past, current, and future, because
we know this is very important, and it will be things that will be clearly discussed at
our upcoming council meeting and will be deliberated by council.
I will also tell you that we're not alone; it's not just NHGRI.
The CSER program has been affiliated, like many of our programs, with collaborative partnerships
with other institutes and centers at NIH, and we have at least a half dozen represented
here throughout the day, and we will be talking to them and looking to them for partnerships
coming out of this, because there's a lot of things that will be discussed and they'll
be very interested in.
And finally the broader community is listening in, that's why we're spending the extra resources
to videocast this live, and to video archive it, because we will ultimately be interested
to hear what the community has to say as well.
We really do want broader input even beyond the people in this room.
So that's what I wanted to do to set the context.
I think I've done this successfully on time, if I know the schedule.
Although if there's any immediate questions, I'm also told that there's a little bit of
time for questions.
So thank you.
Lucia Hindorff: We do have a couple minutes for questions
if there are any for Eric.
Eric Green: We're good?
Oh, and I guess the last thing I should say, I do have to apologize.
I said this is an incredibly valuable meeting, it really is, and unfortunately, headquarters
of an NIH wide meeting got scheduled on top of this that I have to go to in the middle
part of the day.
So I'll be for a while, I have to disappear for the middle part of the day to go to campus
for a meeting, but I will be back here during the last session, especially the summary wrap
up session.
So, with that, I will turn it back over to Lisa.
Lucia Hindorff: Great.
Thank you, Eric.
And now I'd like to introduce Teri Manolio, the director of the division of genomic medicine
at NHGRI to talk to us about NHGRI's genomic medicine portfolio.
Teri?
[end of transcript]