Eric Green: Thank you, Francis, for that terrific opening
talk.
I'm Eric Green, director of the National Human Genome Research Institute.
And I want -- as a co-host to this meeting, I want to thank all of you for coming as well,
and join the others in saying what I think a spectacular opportunity this is to gather
all of you.
And thank you so much for traveling far distances, in some cases, to join us for the next two
days.
What I was asked to do was to describe the National Human Genome Research Institute's
portfolio in genomic medicine.
Now, by way of history, recognize that we are one of the 27 institutes and centers that
make up the National Institutes of Health, and we were created by the U.S. Congress just
before the beginning of the Human Genome Project to lead NIH's efforts in the Human Genome
Project.
And for many years, that was the major focus, of course, of what our institute did.
But about 11 years ago, when the Human Genome Project ended, of course we reoriented our
mission, in many ways, to take on the spectacular opportunities afforded by having sequenced
the human genome, and in many ways now focus on advancing human health through genomics
research.
What I want to tell you about in particular is the more genomic medicine oriented aspects
of our portfolio.
And one of the things we have done in particular of the last couple of years is make sure we
have a very clear definition of what we mean by "genomic medicine."
In fact, we went through a formal process, both internal to the institute and involving
some of our advisors, to make sure we all agreed upon what we meant when we said "genomic
medicine."
And this is the definition we settled on: "an emerging medical discipline that involves
using genomic information about an individual as part of their clinical care, for example,
for diagnostic or therapeutic decision-making, and other implications of that clinical use."
And there are several things to point out about this definition.
First of all, it's purposefully narrow, and we wanted to make it that so it wasn't all
things to bring under the umbrella of genomic medicine.
And by "genomic" we mean direct information about nucleic acids, DNA or RNA.
And while we recognize downstream products are important, they're just outside this immediate
view that we have, and downstream products such as proteomics, metabolomics, and so forth.
We keep this strictly focused on analyzing and information about nucleic acids.
And finally, we really, metaphorically, view this as a key destination for attaining out
mission for improving health through genomics research.
This is where we are heading and very much where the institute is focused on as a journey
that began with the completion of the Human Genome Project and aims to realize genomic
medicine broadly defined.
But as Francis alluded to is absolutely the case, there's going to be many, many steps
involved in this.
We can see some of these steps, and some of them we haven't even anticipated yet.
But our institute is focused on trying to travel this journey, figure out what the barriers
are, and do research that would allow us to make this progression in a productive way.
So what has the institute done?
Well, literally the day the genome project ended, as was very much part of the culture
of genomics, we published a strategic vision of what was needed starting the day the genome
project ended.
That was in 2003.
And while that was a very effective strategic view at the time, it certainly didn't even
last the decade.
And in -- or it didn't last a full decade, and we found ourselves in need of a new strategic
vision a couple of years ago, and so indeed, in 2011, we published one.
And the key distinguishing feature of this strategic vision was an absolute clear articulation
of the clinical application of genomics, which I don't think we were quite prepared to do
in 2003.
But by 2011, we felt the phrase "genomic medicine" and the reality of genomic medicine was in
close enough view that it was time to be more descriptive of what we thought was going to
be needed in terms of a research agenda to get us to the point of practicing genomic
medicine.
And what we finally settled in on as part of the strategic planning process was a recognition
that there was as series of progressive domains of research activities that were very logical
and that were very effective in leading us down this path towards realizing genomic medicine.
Let me just briefly introduce you to these five domains.
Some are quite familiar to us because we had been involved in them for a long time, such
as understanding the structure of genomes.
And then going on in efforts like ENCODE, understanding the biology of genomes.
But probably a little more new to our institute was a clear articulation of research objectives
related to human disease, recognizing that doing genomics research to understand the
biology of disease was a critically next important next step.
And then moving on and looking at genomic research to advance the science of medicine,
but also recognizing that we needed to demonstrate that this was going to truly improve the effectiveness
of health care.
So these five domains became, if you will, a research framework for almost everything
that I think the institute is doing now.
And the centerpiece of our strategic plan we published in 2011 was this figure, it was
Figure 2, which depicted these five domains of research activity over different time intervals,
and these density plots simply represent, in a graphically fashion, different stages
of -- different sets of accomplishments and when they occurred and where they occur relative
to these five different domains, including predicting into the future.
So, these first two domains would largely be regarded as more basic science-oriented
activities, understanding genomes both structurally and functionally, and these three domains
bring us more into, if you will, applied genomics, either looking specifically at disease, processes,
or more clinical application in the fourth and the fifth domain.
And this starts to focus in much more on what we mean by genomic medicine.
But let me clarify further, because we certainly find in discussions that sometimes people
will lump all three of those in and call them genomic medicine.
What we mean by this domain three is discovery research, establishing genotype-phenotype
associations for human diseases.
I list several such examples that one would easily consider to fall under this middle
domain, domain three, of discovery research.
The fourth domain puts us more to the clinical realm in terms of doing clinical validation
studies to assess the outcomes from using genomic information for clinical care and
digging deeper to do research to demonstrate that truly there is validation associated
with the use of genomic information in this way.
And then domain five is really clinical implementation, truly developing processes for using genomic
information for clinical care.
Interestingly, we don't regard domain three as genomic medicine, even though, at the moment,
it is the probably the largest single block of funding we are doing is in disease-oriented
work using genomics.
But this is not what we mean by genomic medicine.
What we truly mean by genomic medicine are domains four and five.
So this is absolutely much more in clinical validation and the clinical implementation
stages of this five-domain progression.
So with that in mind, let me give you examples.
I'm going to give you six major areas of NHGRI programs in genomic medicine; mostly you're
going to hear about this from other speakers.
As Francis alluded to, some sort of cutting edge, leading edge, or lowest-hanging fruit,
if you will, in terms of opportunities in genomic medicine are clearly in the cancer
genomics realm.
Many activities we have going on in this, including some of the pilot projects you're
going to hear about later, but also we, coming out of The Cancer Genome Atlas, a joint venture
between our institute and the National Cancer Institute, are new discussions between those
two institutes about new opportunities one can envision in the future for doing more
really, truly clinical applications of genomics for cancer care.
So it's clearly an area we are involved in.
Another low-hanging fruit, if you will, cutting edge, relates to pharmacogenomics, one that
I think many, many investigators around the world actually are certainly pursuing.
And coming up later this morning you're going to hear from Dan Roden, who's both going to
tell you about the eMERGE network, but also a component of the eMERGE network that now
is -- represents NHGRI's investment in pharmacogenomics research.
A third area of programs for our institute I regard as I call them "test drive programs":
taking out genomics in the clinic as a test drive, if you will.
And you're going to hear from others about two such test drive programs.
Lucia Hindorff is going to tell you about our Clinical Sequencing Exploratory Research,
or CSER program, and Geoff Ginsburg is going to tell you about a brand new effort called
Implementing Genomics in Practice, or the IGNITE Consortium.
We're also very interested in opportunities such as in the newborn period, and we have
a new program on newborn genomic analysis.
In particular you're going to hear from Anastasia Wise, who's going to tell you about a new
program we have in partnership with another institute at NIH, the National Institute of
Child Health and Development, and our Newborn Sequencing Program.
Two other -- the last two areas relate -- the first one relate to what I would call clinical
genomic information systems, and here's something we hear from many people, from many of our
grantees and many of the people when I travel around and talk to people, the recognition
that there is this onslaught of information about genomic variants and as they relate
to disease.
And these are pouring into the clinic in principle and eventually when find their way into electronic
medical records.
Practicing health care professionals are overwhelmed by that incoming data and information about
publications.
We need to develop better knowledge bases, better processes for establishing those knowledge
bases that will simply allow practicing health care professionals to know what it means when
they encounter a genomic variant in a patient.
And so just out of the gates is new initiative called ClinGen, or Clinical Genome Resource,
that we are creating.
We're not going to have a talk about this because it's something you clearly will want
to be hearing about and be monitoring.
It's our investment in this important clinical information arena with respect to genomic
variations and genomic information.
And finally, our last area relates to sort of the ultra-rare genetic disease diagnostics,
and here you need to look no further than the literature to recognize the remarkable
number of review articles that are now appearing where clinical sequencing is truly being done
as part of diagnostics, especially for ultra-rare genetic diseases.
And Francis introduced to you the Undiagnosed Diseases Program, and indeed this is a NIH-wide
program that is now going beyond just what's happening at the NIH as a program to a network
of centers around the country, and NHGRI is one of the lead institutes in helping lead
this, both with respect to what's going on at NIH and with respect to this network.
So just to add a few more details to what Francis mentioned, we're going to build upon
the successful experience with the Undiagnosed Diseases Program, which was just at NIH, to
now build a network of these centers around the country to improve the diagnosis and care
of patients with undiagnosed diseases, facilitate research into the etiology of undiagnosed
diseases, and create a highly-collaborative research community to identify best practices
for the diagnosis and management of undiagnosed disorders.
So, in summary, those are the six major areas of genomic medicine programs that NHGRI is
carrying out.
You know, historically, and even right now, the major emphasis of what we're doing is
very much in the arena of understanding how genomes are put together, particularly how
they're working, how genomes function, and this will continue to be a high priority for
the rest of this decade and beyond.
But as I alluded earlier, probably our biggest investment right now, if you follow the dollars,
is using genomics to understand the molecular basis of human disease.
The six areas I just introduced you to, the genomic medicine portfolio of the institute
is very much about the future.
It's not so much about advances that are going to happen this decade.
It's building a foundation for what we think are going to be spectacular advances in the
application of genomic medicine beyond 2020.
Finally, if you are interested in monitoring or following what's happening at the Institute,
just a few months ago I created a monthly email update that I send out to anybody interested,
and I guarantee you we will be chronicling our programs, both current and future ones,
in these monthly newsletters I send out.
If you are interested in receiving them, especially with -- I'm delighted to communicate to international
audiences, if you just go to the simple URL, genome.gov/director, and down there you will
find the link that will allow you to sign up for our listserv, and you would be able
to get these monthly updates from me if you're so interested.
Finally, I just want to say a couple words about the special thing that's going to happen
tomorrow morning for this group.
We thought it was too good of an opportunity to have you here in D.C., especially downtown,
and not be able to see something that NHGRI is particularly proud of.
It relates to what I was just talking about.
Part of the responsibility of seeing a genomic medicine research program grow with time is
the recognition that part of the success is going to require public engagement, public
education, and public literacy in genomics.
And one of several things we're doing, but certainly the flagship now, is a partnership
we developed with the Smithsonian Institution, in particular the National Museum of Natural
History, to create an exhibition at the National Museum of Natural History.
This came out of some discussions we had a couple of years ago, and then ended up in
the decision to create such an exhibition, and that exhibition just opened fairly recently
and really just down the street from here, and we thought it was just too good of an
opportunity, so we rearranged the scheduled and have all of you have breakfast there and
be able to tour the exhibition for an hour, hour and a half.
So you'll be entering that building tomorrow morning.
This exhibition just opened earlier this year.
It's at the National Museum of Natural History.
It's a fairly sizeable exhibition, as you'll see.
And it's in Hall 23; if you don't remember Hall 23, there's two ways to remember.
First of all, humans have 23 pairs of chromosomes.
That's one way.
[laughter]
But if you get lost, although we won't allow you to get lost because you're actually getting
into the museum before it even opens, but all you've got to do is find your way to the
Hope Diamond and take a left.
That's all you do to find that room.
Immediately adjacent to the Hope Diamond, the number one visited exhibition at this
museum.
You'll meet tomorrow the director of the museum, Kirk Johnson, and he will proudly tell you
it's the number one visited natural history museum in the world.
It's the number two visited museum in the world, second to only to the Louvre in Paris.
This will be resonant at this museum for one year, and you will see it tomorrow morning,
and then it's going to tour North America for four to five years.
So you will be there before the museum even opens, but we'll keep you just in Hall 23
because I don't want you wandering around, you'll get lost with a bunch of dinosaurs.
[laughter]
So, with that, and if you're interested in learning more about the exhibition, or read
about it or see a preview before you get there tomorrow morning, a simple website -- not
a simple website, a simple URL, unlockinglifescode.org, brings you to a spectacularly wonderful website
associated with the exhibition.
And so please look at that and tell your colleagues about it, especially those in your home country
who can't travel here to see it.
They can take a virtual tour of the exhibition at this website.
Thank you for your attention.
I look forward to spending the next two days with you.
[applause]