Francis Collins: Thank you.
Oh, and for a kind introduction, and thank you especially for the hard work that's gone
into organizing this exceptional meeting.
Speaking for NIH and all the folks who are here, we're really welcoming this opportunity
to hear from the community about where we need to go next with this very exciting area
of science, which is just bursting with opportunity and potential for understanding aspects of
human health that had been outside of our reach until recently and are now coming forward
in a way that all of us are truly excited about.
And as Owen has said, we are at a critical juncture here where the Microbiome Project,
having lived for a while in the Common Fund, is now moving out into lots of other territories,
lots of institutes involved, and it is a great moment to hear from all of you about where
those opportunities are most compelling.
We, at NIH, live, unfortunately, in challenging times when it comes to resources, with things
like the sequester having put us in a historically difficult position as far as being able to
support all the science we would like to.
All the more reason why we have to think carefully about how to set priorities, and getting input
from the scientists in this room on this topic is a great example of the kind of thing that
we're trying to do more and more of.
So Owen, thank you and your team of organizers for making this possible.
Believe me, NIH is listening, participating, delighted this is happening.
My task, I think, is to basically set very briefly a little bit of the historical context
here, and then I'm going to pass off to Eric Green who can tell you where we are right
now in terms of the things that NIH has supported in this Human Microbiome Project, and then
that will sort of make it possible for all those speakers who follow over the next couple
of days to go forward from that with exciting new ideas.
And that's exactly what I think the intention is of the meeting.
My title here I thought about a bit, and you could basically blame me for being a little
hyperbolic here with all of these superlatives: supercharging, and superorganism, and not
to mention the attempt at alliteration here.
But it is a superorganism we're talking about in terms of the interactions between hosts
and microbes, and the way in which we would like to see that move forward is to move that
science in ever more powerful directions to understand how that works, how disruptions
in that superorganism result in health and disease, and what we could do about it.
So very briefly in terms of the background, this certainly fits the mission of the NIH
quite powerfully and compellingly.
You may know NIH has this twofold mission of fundamental knowledge about the nature
and behavior of living systems, but also the application of that knowledge to extend healthy
life, and reduce illness and disability.
Microbiome fits smack in the middle of this longstanding mission of the largest supporter
of biomedical research in the world, the National Institutes of Health.
Going back to sort of the historical side of this, you could say that Microbiome was
a very natural fit for NIH, going back to our very original origins.
Many people aren't aware NIH was actually established a little over 125 years ago as
a hygienic lab testing samples for infectious disease in a small laboratory, not here in
Bethesda at that point, but on Staten Island.
And over the course of time, of course, NIH playing roles in many other ways that feed
into what we're going to talk about as far as the microbiome, including, as you can see,
the photograph here of Nuremberg, the Genome Project of course fitting in here.
And interestingly, wondering where this genomic return to microbiology comes from, and where
the term microbiome first arose, it seems that it came forward in this article by Joshua
Lederberg and Alexa McCray -- Alexis at the National Library of Medicine, where the formulation
of words that began in -ome was put forward in a rather categorical and somewhat tongue-in-cheek
way.
But Lederberg very much, as you can imagine, having won the Nobel Prize for his own work
in microbiology, was attracted to the term microbiome "to signify the ecological community
of commensal, symbiotic, and pathogenic microorganisms" -- pretty good definition -- "that literally
share our body space and have all been ignored as determinants of health and disease."
And here again the term superorganism: "We should think of each host and its parasites
as a superorganism with respective genomes yoked into a chimera of sorts."
Well said, Josh.
Of course, the ability to be able to sample the microbiome as we are now talking about
depended very much upon the ability to be able to collect nucleic acid information on
organisms, many of which are not directly culturable.
And so I'm sure much of today's conversation will relate to the fact that that has become
within reach because of this curve -- as you can see, and everybody who studies genomics
is fond of showing curves like this -- dropping the cost of a human genome from $100 million
back in 2001 to now, as current estimates, exactly $5,671 or thereabouts.
And, of course, the technology to do that has advanced, and that's why this has become
possible for machines that look like this, some of which, of course, are still producing
lots of data, to things that are more microscaled, in this case, an Ion Torrent, but there's
lots of other competing technologies, and this has not anywhere near exhausted its potential
for reducing costs and increasing throughput.
And that has been such a phenomenal, wonderful ride to be on in the microbiome, and it's,
of course, in lots of other applications as well.
So how did microbiome become, at NIH, a project called the HMP, and how did it find its way
into support through what was at one point called the Roadmap, and then became the Common
Fund?
I asked Jane Peterson, who was engaged in the early days of this, to do a little walk
through memory lane and remind me of sort of how this all got started, and she reminded
me of a Valentine's Day evening meeting at NIH, all of three hours, which a number of
the people in the room were present for, where this idea of organizing an effort to focus
on metagenomics, which ultimately, I think, we decided to prefer the term the Microbiome
Project, might be a very timely thing to do, bring together investigators and sequencing
capabilities, and make this an effort which crosses institutes, and therefore fit quite
nicely into what was, at that point, called the Roadmap, an effort that Elias Zerhouni
had put together, and shortly after that became formalized because of congressional authorization
into the Common Fund.
All of that, I think, timely because here, in 2006, it was beginning to become clear
there was real potential here to apply the kind of DNA sequencing efforts that were becoming
more and more achievable to do this kind of metagenomic analysis.
So the argument, then, that this would fit nicely into the Roadmap, and ultimately the
Common Fund, was a pretty convincing one because the whole point of those kinds of means of
support at NIH were to support projects as you see here that should be truly transforming,
that would require participation of NIH as a whole -- no single institute or outside
entity would be likely to do this on their own -- to place the outcomes in the public
domain -- and again, I'm glad to hear in Owen's description that's something we have to keep
pushing as this moves into other sources of support -- and need a development, an incubator
space, to jumpstart the field because, at that point, it wasn't clear that the microbiome
was going to move forward as swiftly as it might without that kind of incubator opportunity.
And so this, then, was endorsed, brought forward fairly quickly as a Common Fund Project.
Lots of people worked hard on the effort to make that a reality.
I particularly, again, want to mention Jane Peterson and Pam McGinnis, both of whom put
a huge amount of effort into trying to organize this component of what the Common Fund was
going to support, and put together ideas about exactly what might happen, held various workshops,
collected ideas from experts and interested parties of all sorts, and then proposed a
massive -- [laughs], my standards of 2007 probably rather trivial by today -- a massive
microbial sequence project.
And then articles got written about what this might look like.
This is a bunch of things from 2007, just as the effort was getting underway.
A logo appeared, various diagrams about exactly how many more of them there are than of us,
which are part of all of our opening slides now when we talk about this, got generated,
and we were off to the races.
And, of course, this was not just a U.S. area of interest.
The European interest had actually been there at least as early as the United States, and
so it was important to put together as much as possible the international efforts through
this International Microbiome Consortium with members and research programs that you see
listed here, and certainly going forward, we want to be sure to take full advantage
of all of those connections and collaborations.
Well, then I'm going to leave to Eric to describe a lot of what actually got done scientifically
as a result of all this, but, as you know, in the course of just a few years, it was
possible to produce really quite a remarkable foundation of data about the structure, function,
and diversity of a healthy human microbiome framework for research, and increasingly focus
on specific disease areas where the microbiome seems to be playing a role, many of which
are going to be discussed in much greater detail at this really important milestone
meeting.
And out of that, I think it'd be fair to say, increasingly, institutes that had been participating,
because everybody at NIH is involved in some way in a Common Fund project as either a participant
or a cheerleader, became increasingly clear that the way this direction was going would
require institutes to actually embrace within their own portfolio some of the clinical applications.
And I want to just show you how that has come about because I think you'll be pleased to
see the way in which the institutes are embracing this.
This diagram, for those of you who don't know the ins and outs of NIH, just shows you the
27 institutes and centers at NIH that make up the way in which our budget is allocated,
and the way in which decisions are made about research priorities for the most part.
The Common Fund is the exception, but only represents a little less than 2 percent of
the budget.
The rest, the 98 percent, is out here in these institutes.
Before 2008, you can see a few of these institutes, particularly NIGMS, for instance, and NIAID,
and a few others here, NIDCR, and invested in this, but many of the others not at that
point, now five years ago, engaged in microbiome research support.
Over the course of the next few years, those numbers begin to grow, and now, in 2013, you
can see a very substantial fraction of the institutes are in fact engaged in supporting
this, recognizing the time has come to take the foundational information produced by the
Common Fund-supported enterprise, and begin to see how that plays out in health and disease.
And that should be seen as good news.
If you try to factor that then into funding support, this graph shows you for '10, '11,
and '12 what has happened both in terms of the number of grants and contracts, which
is in orange and the green, which is the extramural funding, which as you can see for FY '12 had
climbed up to about $180 million, and the expectation is because the scientific opportunity
is so compelling, that that number, provided that we don't get further hammered by additional
budgetary distress, ought to continue to grow.
So I hope you'll see that as a sign of encouragement that we have begun to move into this phase
of broad NIH interest and support for the areas that are represented at this meeting,
and that, therefore, it's a very timely moment to have the input from this kind of a group
about how that's going and where it needs to go.
Just have to mention that, of course, one of the aspects of this that feeds into another
program that NIH is now putting some significant resources is, of course, the very large production
of data that comes out of this kind of analysis, particularly when it involves metagenomics
and requires, therefore, some sophisticated analysis to know what's going on.
And we have recently, in a group that I asked to look at our abilities to handle big data,
gotten the message that we have a lot of work to do here.
As a result of that, NIH, in a number of initiatives, including one called BD2K, Big Data to Knowledge,
which was just announced this week, focused on trying to build additional Centers of Excellence
in computational approaches because, clearly, we're going to need that.
And the microbiome is just one example, along with a variety of other approaches: what's
going on in cancer genomics, the new brain initiative that's going to generate huge amounts
of data from neuroscience, and so on.
I also have basically decided we need a key person that covers this issue across all of
NIH, and so we've established a new position called the Associate Director for Data Science.
Very nice that the acronym there is ADDS.
Isn't that cute?
And Eric Green, who's going to speak in a minute, is the acting ADDS, and we're in the
process of searching for a permanent person to take on that very important role.
And that's going to be very relevant, I think, to where microbiome needs to go because the
data needs are going to be both interesting and pretty challenging.
Well, I think it's fair to say that the things we have already learned, in terms of health
and disease with the ability now to be able to sample the microbiome, certainly in the
GI tract but also in other areas like skin, have told us already surprising things that
would not have been predicted a few years ago about exactly how this superorganism works,
and how things can go awry, and I suspect much more is still to come.
You have the feeling that we've just begun to scratch the surface, and there's a lot
of complexity here, but it's beginning to look as if the fog is lifting, and we're able
to see some of the principles and some of the conclusions that might even become, before
long, actionable, and we'll hear about some of those at this meeting in fact.
So I just wanted to, in a few moments there, kind of set the stage of how we got to this
point, particularly to express to all of you how much NIH is excited about this area of
science, how it is one of those areas that we think has really arrived at the moment
where it particularly was in need of nurturing as a foundational effort, and is now bursting
with potential that all of the institutes at NIH are interested in taking part in.
So congratulations again to the organizers of this effort.
We will look forward to seeing what comes out of this, glad that there will be a report
that can be all be absorbed, glad that you're webcasting this so the people not in the room
can also hear the presentations, and that will stimulate, I'm sure, a lot of their thinking.
So many thanks to all of you.
Have a great meeting.
It's a pleasure to be here.
[applause]
Owen White: Thank you, Dr. Collins, for setting the tone
and staying on time.
I appreciate that.
Our next speaker is Dr. Eric Green.
I think he's already been introduced, so come on up.