Eric Green: Well, thank you all, and it's a pleasure to
be here and to follow on Francis to really help set a context and a little more detail
for this remarkable three-day meeting.
I would point out immediately that the Human Microbiome Project is led by multiple institutes.
I think there's four of us -- four institutes in particular have a lead, but many other
institutes involved, and I'm speaking on behalf of what have could have been several different
institute directors who could easily represent this sort of an update, if you will, about
the state of the Human Microbiome Project at NIH.
So shown here are the locations of the six initiatives and the numerous researchers involved
in the first phase of the Human Microbiome Project called HMP1.
This includes clinical lab, sequencing centers, data analysis and coordination center, and
these groups together coordinated two types of cohort studies.
It also includes the computational tools in ELSI program.
These groups contributed tools and expertise in the design as well as the analysis of the
HMP1 data.
And also shown are technology development projects focused on new ways to analyze the
thousands of previously-uncultured microbial species that make up the human microbiome.
Now, HMP1 is a community resource project.
The goal of HMP1 was to survey the microbiome in humans through two kinds of analyses: first,
taxonomic analysis of microbial communities living in and on the human body; and two,
analysis of the collective genetic potential of these genomes through metagenomic analyses.
Now, the generated community resources included a catalogue of reference bacterial genomes
and a repository of their cultures, taxonomic and metagenomic data, and clinical and phenotypic
data from the cohort studies.
Nucleic acid extracts from the healthy cohort study are also available, and future resources
may include genome sequences of the individuals, the human subjects, participating in these
cohort studies, as well as cell lines that derive from these individuals.
In total, there were six initiatives in HMP1.
All of the 400-plus member consortium interacted through a data analysis -- a data analysis
and coordination center.
The survey on HMP1 was conducted in two kinds of cohort studies: first, shown here, a study
of 300 healthy adult men and women; and then second, a group of 11 demonstration projects
which set out to evaluate the microbiomes associated with particular diseases.
And many people contributed to the development of this extraordinary research consortium
who interacted around the central activities of sample collection, and ultimately, data
analysis, and doing it in a highly choreographed way illustrated on this particular graphic.
Now, the HMP healthy cohorts study is the most extensive analysis of the microbiome
in healthy adults conducted anywhere in the world to date.
Five major body sites were studied in HMP1: nasal and oral cavities; the skin; gastrointestinal
tract; and the female urogenital tract.
An extensive list of inclusion and exclusion criteria, along with clinical verification
that the subjects were free of disease at all body sites, set the bar for collecting
the least disturbed microbiomes possible from the subjects.
Also, no other study even today has simultaneously sampled and analyzed the microbiomes of multiple
regions of the human body.
Now, as shown here on this graphic, each region of the body was home to a unique community
of microorganisms.
Upon reflection, this probably isn't terribly surprising when you consider the different
environmental conditions, whether it's oxygen level, pH, et cetera, and, in particular,
nutrients such as organic acids, proteins, and so forth that would be found at each of
these sites that would promote the growth of different microbes capable of taking advantage
of the unique habitat.
And surprisingly, perhaps, the composition of the microbiomes of these healthy adults
did not cluster by typical human factors we think that are important such as gender, age,
weight, ethnicity, and race.
Now compared to other metagenomics projects, HMP1 generated the world's largest sequenced
data set.
The graph shown here plots the total number of terabases of DNA sequenced deposited in
public repositories since the practice of shotgun sequencing for metagenomics projects
began in 2006.
Now there are three sources of microbiome data plotted on this graph reflecting data
from -- for human, animals, and the environment, in red, black, and green respectively.
Note that HMP1 generated about seven terabases of whole genome shotgun sequence data that's
not shown here, but after removal of the human sequence, 3.5 terabases, which is what's reflected
here, of microbial metagenomic sequence data is left, considerably larger than any other
project to date.
Now analysis of the HMP1 metagenomic data suggests that in the United States, each individual
may support something on the order of 1,000 species of bacteria, but there may be a global
pool of upwards of 10,000 microbial species shared among healthy adults.
These 10,000 microbial species may contribute to a global pool of something on the order
of 8 million unique microbial genes comprising the total genetic potential of the microbiome
in humans.
Well, needless to say, and as Francis started to highlight, analysis of the rich data set
from the healthy cohorts study involved extensive work by HMP consortium members whose efforts
culminated in many papers, but, in particular, in this set of key papers in 2012.
Two HMP flagship papers were published in Nature in June of 2012, just a little over
a year ago, and a set of 20-plus companion papers, reports from individual projects,
that comprised different data sets, as well as on the development of computational methods
underlying analysis approaches, were simultaneously published in PLoS in an HMP collection of
papers that's highlighted here.
Well, HMP was established to serve as a catalyst for the human microbiome field more broadly,
and it's made a major impact on the field in numerous ways.
One measure of this impact comes from -- in terms of the numbers of HMP1 publications
and their citation frequency.
And so shown here is a graph of the total number of HMP1-funded publications in PubMed
each year, and that's the blue line, and the average number of times each paper has been
cited, and that's the red bars, with the citation frequency calculated from Google Scholar data.
The rate of publishing HMP1 papers has increased at an impressive rate, as you can see, with
a grand total now being about 350 as of May of this year.
And as you can also see from the red bars, in particular HMP1 publications are clearly
being well-cited.
Another measure of success one might say is the impact of HMP1 program in terms of the
remarkable amount of media attention that the field is receiving through the efforts
of this consortium, both the lay media but also the scientific media.
Now many types of media have shown interest in HMP1 including print, radio, TV, both interviews
as well as documentary-length pieces.
This is just data that has come in to the NHGRI, the institute I direct.
Our communication office alone received a total of 70 media inquiries about HMP1 from
2007 to 2012 as shown here, with blue being domestic inquiries and red being foreign inquiries.
The number of media inquiries steadily increased with time and peaked over 30 in 2012, the
year the HMP1 flagship papers came out, and many were multiple inquiries from these sources
showing sustained interest from media outlets in the field of microbiome research in general.
But, of course, let me emphasize, this does -- this only reflects what came into our communications
office at one NIH institute.
Needless to say, I'm quite certain these numbers would be higher if we were able to tally all
the media inquiries coming in at the other individual institutes that are involved in
microbiome research as well, and those also involved in HMP1.
Well, recall that HMP1 focused on mapping the human microbiome, but a question immediately
arose from these analyses.
If there's a global pool of 8 million microbial genes in the human microbiome, what are those
genes and those gene products doing?
And certainly an analysis of the biological activity of all 8 million genes would be a
nearly impossible undertaking.
We would need to measure the gene expression and proteins coded from all of these genes,
and figure out what they're doing.
And trying to understand all of the metabolic intermediates and byproducts in human metabolism
hasn't been completely done yet.
How can we possibly do this when in orders of magnitude more metabolites produced by
the microbiome?
Well, these questions are what gave rise to HMP2 which will take place from 2013 to 2015.
And HMP2, which is a Common Fund -- a continuation of a Common Fund effort is focused on a more
manageable objective: generate a dataset of microbiome and relevant host genomic and biological
properties from a well-characterized cohort of a specific microbiome-associated disease;
produce those data as a community resource; and then ensure that the datasets can be queried
by the larger research community.
Though by no means complete, this program will create the first such resource of multiple
properties of the microbiome in the context of a known disease.
This resource will help the scientific community wrangle with the almost overwhelming numbers
of features of the microbiome into a manageable subset of features in order to be able to
evaluate which properties or combinations of properties appear to be the most informative
for deciphering the role of the microbiome in human health and disease.
Well, HMP1 will start this fiscal year, and we plan to support two awards for a total
investment of the NIH Common Fund of $5 million per year, and, of course, this is in addition
to whatever will be going on in microbiome research at the individual institutes, and
you can see from Francis's presentation, the number of institutes indeed funding microbiome
research is growing at a steady pace.
And finally, and just to close, for more information about HMP1, including historical information
and HMP2 as it begins to get traction, as well as all of their resources, publications,
and news, is always going to be available on the NIH Common webpage dedicated to the
Human Microbiome Project, the URL given here.
So let me just close by saying that on behalf of the collective NIH leadership, I want to
congratulate those of you who've participated in HMP1.
All of those researchers and their remarkable accomplishments and contributions to the field
really catapulting the field forward, as Francis alluded to as well.
And we really look forward to similar successes for HMP2.
These efforts truly have catalyzed the field of microbiome research in a very productive
way, and all of you should be very gratified to know that your contributions have been
very important for those advances.
So thank you very much for your time, and with that as a context, I think it's very
exciting to now start to hear the science in greater detail in subsequent talks.
Thank you.
[applause]
Owen White: Okay.
We're going to thank our two speakers one more time.
[applause]
And now it's time to begin our next -- our first session.
So Melody [spelled phonetically] --
Female Speaker: Hi.
It's my privilege to introduce our keynote speaker today, Dr. David Relman, a physician
scientist who's a professor of medicine and of microbiology and immunology at Stanford
University.
He studies the indigenous microbiota in human and marine mammals.
He's provided insight into the oral, gut, and female reproductive tract microbiota.
Basically, he's a -- one of the pioneers in the field to which this meeting is devoted.
He's also pursued studies on pathogen discovery, host-pathogen interactions, and mechanisms
of diseases and conditions such as dengue fever, fevers of unknown origin, and pre-term
birth.
He has served on numerous panels, committees related to microbial threats and biosecurity.
He's the recipient of numerous awards, such as an NIH Directors Pioneer Award and the
Infectious Diseases Society of America's Squibb Award, just to mention a few.
He's a member of the National Academy of Sciences, and he's served as the president of the Infectious
Diseases Society of America 2012 to 2013.
And last but not least, anecdotally, his good citizenship extends to the community in which
he lives.
He's the chief medical officer for the Haight-Ashbury Medical Centers.
So please join me in welcoming Dr. David Relman.
[applause]