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Eric Green: Okay. Well thank you, Rudy, and let me just
jump right in. I'll start by reminding you, as Rudy did, that the open session of our
council meetings are being webcast live. In addition, and what is now our routine, the
open session of all council meetings are being videotaped and made available as an archive
on the Web, and that includes both the presentations themselves as well as all the various associated
documents. And for anyone new to our council meetings, I want to make you aware there's
an electronic resource associated with my director's report that many people help put
together. It's sort of analogous to a supplemental materials that are often associated with published
papers, and can be accessed at this convenient URL shown on the slide. And the slides that
I'm showing during my director's report are available electronically at this site, both
as a PDF file and also as the native PowerPoint file. And many of the slides are associated
with the specific documents or relevant websites that we want to point you towards. It's indicated
as a document number on the bottom right, and then references material that you can
then access at the website given here on the slide. In addition to the video archive that
I mentioned earlier, this webpage and all the link documents that are archived in NHGRI's
website, genome.gov, are done so as a permanent historic resource for future use.
Now, there are multiple other presentations during my ‑‑ during the open session of
this council meeting. My director's report is thus tailored around these presentations
so I'll not discuss in any detail the topics that others will be covering. When I'm done
with director's report, for starters, we'll have a presentation by Dr. Gary Gibbons, the
new and recently arrived director of the National Heart, Lung, and Blood Institute.
We'll then have three project updates from NHGRI staff members. Brad Ozenberger is going
to talk about The Cancer Genome Atlas. Simona Volpi is going to talk about the Genotype-Tissue
Expression GTEx Project. And Jane Peterson is going to talk about Human Heredity and
Health in Africa Project, H3Africa. NHGRI's Rongling Li will then present the Biennial
Report on the Inclusion of Women and Minorities in NHGRI-supported research. And we'll then
have a major update about our Centers of Excellence in Genomic Science, or CEGS Programs; specifically,
hearing from Jeff Schloss of NHGRI, followed by presentation from two CEGS grantees who
happen to be council members as well: David Kingsley and Deirdre Meldrum. And the last
topic in the open session is the annual review of the statement of understanding between
the council and NHGRI, which will be presented by Rudy Pozzati.
So for the rest of my director's report, I will cover the seven areas listed here together.
We have found that this provides a very nice framework for reviewing the relevant topics.
And let me start with some just general NHGRI updates.
Well, this council meeting marks the first since we implemented the new substantive reorganization
of NHGRI. In fact, it's really the most significant reorganization of the Institute since the
beginning of our enterprise. Implementation of this new organizational structure which
council has been hearing about for the better part of a year and which mostly affects our
Extramural Research Program, actually took place on October 1 of 2012 at the beginning
of the current fiscal year.
And shown here is a slide you've seen before, showing the institute's new seven-division
structure. In particular, note that four new divisions constituting the Extramural Research
Program. Significant amount of hard work went into many nuances involved in changing our
organizational structure, but I can report that, overall, the transition has been a very
smooth one.
Let me just pause for a minute and offer my sincere thanks and appreciation to the entire
staff of NHGRI's Extramural Research Program. In particular, for enduring some fairly significant
changes to their part of the Institute. I also want to thank our outstanding administrative
staff who did a tremendous amount of behind‑the‑scenes work to make such a major reorganization possible.
And lastly, congratulations to our new leadership team who are now in their new positions as
division directors and division deputy directors. In fact, you'll be hearing from most of these
individuals during this council meeting.
Finally, I have one announcement that I want to make, and that is, recall that I have appointed
permanent directors for all these divisions except for the Division of Genomics in Society.
And on an interim basis, NHGRI Deputy Director Mark Guyer is serving as the acting director
of that division. But I'm now ready to move forward in identifying a permanent director
for the Division of Genomics in Society, and, as a result, in the next few weeks, I will
launch a search to identify this division director. And once a few more details are
worked out, you can expect to receive an email from me and to see advertisements with information
about this important recruitment.
Another area of NHGRI updates relates to the year 2013, which will be a spectacular and
celebratory year for both the Institute and for the field of genomics. Recall that 2013
will mark the 60th anniversary of the famous publication of Watson and Crick reporting
the double‑helical structure of DNA, and even closer to our own hearts, 2013 will mark
the 10th anniversary of the completion of the Human Genome Project.
As you might expect, NHGRI has been particularly focused on appropriately commemorating the
Human Genome Project's 10th anniversary. So we brief you ‑‑ briefly update you about
several major components of our yearlong celebration. For starters, NHGRI will be hosting two sets
of talks at NIH in the coming months to celebrate the Human Genome Project's 10th anniversary.
The first of these will be given by three pairs of speakers listed on the left side
of this poster. Specifically, they'll be paired presentations by Bob Waterston and John Sulston
on Thursday of this week; Isaac Kohane and George Church in March; and Caryn Lerman and
Alexandra Shields in May.
Then, in April -- on April 25th, which is DNA Day 2013, NHGRI will hold a day-long special
symposium with participating speakers listed on the right side of this poster. As you might
imagine, we've lined up a real all‑star cast for this symposium including council
members David Kingsley and David Williams, as well as speakers such as Sarah Tishkoff,
Claire Fraser, Jeff Bodkin, Kevin Davies, Nancy ***, Ewan Birney, Levi Garraway, Dan
Roden, David Botstein, and someone named Francis Collins. So you can expect to see a remarkable
symposium on that day.
Rest assured that even if you can't come to Bethesda for any of these paired seminars
or for the April 25th symposium, you'll be able to watch all of these presentations after
the fact via video archive at that we're creating that will be available on genome.gov via our
Genome TV channel of YouTube.
And actually shown here is the dedicated we page with the easy to web URL, genome.gov\hgp10.
That has all the links to the various 2013 celebratory events, including videos of all
these presentations once they're available.
Now, of course, the centerpiece element of our yearlong 2013 celebration will be the
opening of a genome exhibition at the Smithsonian Natural Museum of Natural History. By way
of reminder, we announced at the May council meeting the establishment of a new collaboration
with the Smithsonian to develop a traveling exhibition on genomics. Our partnership with
the Smithsonian has been fabulously productive, and staff members from both institutions have
been feverishly working together on what is a very tight timeline. I can report that we
are currently at the 95 percent design phase. I literally have the 95 percent prints and
information on my desk; I'm reviewing it actively. And we are just a few weeks away from the
initial start of fabrication.
After many months of discussion, we have decided on a title for the exhibition, and I'm pleased
to announce that the "Genome: Unlocking Life's Code" exhibition will officially open on June
14th of this year. While it is resident at the Smithsonian Natural Museum and Natural
History for roughly one year, the exhibition will be located in Hall 23, immediately adjacent
to the hall that contains the Hope Diamond. Starting in late 2014, the exhibition will
travel around North America for four to five years. The organization responsible for traveling
the exhibition is in the process of contacting potential hosting museums and science centers,
and the NHGRI Education and Community Involvement Branch is busily planning local and national
programming associated with the exhibition, both for when it's here in the D.C. area and
then elsewhere when the exhibition tours.
Some of you might have seen the nice shout-out that Nature magazine provided about the Human
Genome Exhibition and their first issue in 2013, listing it as one of the hot tickets
for 2013 in science and art. Thank you very much, Nature.
And finally, I'm happy to report that we have arranged for the second day of our September
council meeting to be held at the Smithsonian Natural -- Museum of Natural History itself,
so as to provide all of you a chance to see exhibition. So more details to follow about
the September council meeting.
My discussion about the significance of the year 2013 as a good segue into the last NHGRI
update, one related to our historical archiving efforts. Over the past few years, I've come
to realize how many materials NHGRI has that are of historical significance, and yet these
various documents, and slides, and photographs, and videos, and other materials related to
the Human Genome Project, as well as those related to every other major initiative that
we have been involved with, from the HapMap project, to ENCODE, to 1,000 Genomes, and
so forth, is incredibly valuable for the history of science.
Well, needless to say, I've also come to realize that we need to get better organized at archiving
these precious resources in a more professional way for science historians to be able to access
and utilize them in the future. So towards that end, we have now hired a professional
archivist and historian, Chris Donohue. Rudy introduced you few minutes ago. And Chris
is working to develop an overall historical archiving plan for NHGRI. Eventually, we aim
to make these materials publicly available.
Meanwhile, I can tell you there's an increasing interest in better documenting the history
of the Human Genome Project in particular, and we're in discussions with other organizations
that are very interested in moving that historical compiling of information forward, in particular,
Cold Spring Harbor Laboratory and the Welcome Trust. And so we've been interacting with
them, and I suspect we'll have more to say about various collaborative efforts about
Human Genome Project history capturing at future council meetings.
So let me move on to some general NIH updates. Well, shortly after the last council meeting,
Chris Austin, someone very familiar to NHGRI, was named the new director of the National
Center for Advancing Translational Sciences, or NCATS. Chris came to NIH from Merck. He
founded and then directed the NIH Chemical Genomic Center, and then later the NIH Therapeutics
of Rare and Neglected Diseases, or TRND program, and was later appointed the Scientific Director
of the NIH Center for Translational Therapeutics. Residing initially -- all that residing initially
within NHGRI, and then later got moved to NCATS. Well, congratulations to our good friend
and colleague, Chris Austin, for this new appointment as director of NCATS.
Richard Nakamura was recently appointed the new director of the Center for Scientific
Review, CSR. Richard Haven, serving as the acting director of CSR since September of
2011. Prior to that, Richard had a distinguished 32‑year career at the National Institute
of Mental Health, NIMH, where he served as its deputy director and later, as its scientific
director.
Well, after considerable study and discussion, NIH has decided not to merge with the National
Institute on Drug Abuse, NIDA, and the National Institute on Alcohol Abuse and Alcoholism,
NIAAA. Instead of a structural reorganization, NIH, will pursue functional integration of
relevant programs from each institute. In doing so, NIDA and NIAA will retain their
institutional identities while strengthening their ongoing efforts to work more closely
with each other and with other institutes and centers, working in the areas of addictions,
substance use and abuse, and related topics.
Last September, NIH joined Faster Cures in hosting a three‑day Celebration of Science
in the D.C. area. The events on one of those days were actually held on the NIH campus
and featured compelling presentations from scientists, patients, caregivers, on topics
such as ***/AIDS, precision medicine, protein-folding neuroscience, and rehabilitation medicine.
There are also discussions with policy makers and industry leaders on the health and economic
benefits of biomedical research. For those interested, videos of the various Celebration
of Science events are available at the links provided in Document 7.
The NIH director, Francis Collins, clearly has some spare time on his hands. He started
his own blog to highlight new discoveries in biology and medicine that are game changers,
noteworthy, or, quote, "just plain cool." Francis has actually been pretty good about
blogging, hosting new materials seven time ‑‑ several times per week, so if you miss
him or you feel so inclined, please feel free to reach out and blog with the NIH director.
The report from the working group on the use of chimpanzees in NIH-supporter research has
been submitted to NIH. Recommendations in the report pertain to chimpanzee housing,
currently awarded projects, size and placement of NIH chimpanzee populations, and a review
process for future research. The report recommends retirement and transfer of the majority of
NIH chimpanzees to sanctuaries at the end of some research projects. Public comment
pertaining to the report is now open through March 23rd, and NIH plans to announce a decision
on the recommendations in late March of this year.
And I will now make a seamless transition from chimpanzees to the federal government's
appropriation process, but don't read anything into the artful choreography, okay?
All right. I just made the transition. Although, we are several months into fiscal year 2013,
we still do not know what NIH's or NHGRI's budget will be this year. I am sure that you
have, like me, been following the recent Congressional debates on government spending and appreciate
the continued budgetary uncertainty under which the government is operating. Here is
what we know at this point. We are currently operating under a continuing resolution which
allows the federal government to continue to operate in the absence of assigning a budget
from Congress. Now this will expire on March 27th. What happens after this date has yet
to be decided by Congress. Congress could pass regular appropriations, legislation to
establish the final budgets for the year, but this is likely unlikely. A more likely
scenario is that Congress will pass a new continuing resolution with a new expiration
date.
The other major factor in the federal budget at the moment is the looming threat of sequestration.
As a brief reminder, sequestration is an across-the-board cut of 2013 budgets mandated by the Budget
Control Act of 2011. In simple terms, what the Budget Control Act means for us is that
there will be major cut to NHGRI's fiscal year 2013 budget unless Congress acts. Originally,
the deadline for Congress to act was January 2nd. However, the American Taxpayer Relief
Act passed on January 1st, 2013, and in doing so, the immediate threat of an 8.2 percent
cut to the NIH budget was averted. We now find ourselves in a new situation: if Congress
doesn't act by March 1st, that on March 27th, there will be a new sequester. This time,
it is being estimated that the reduction in the fiscal year 2013 NIH budget will be less
than the originally projected 8.2 percent.
So, for now, I can tell you that NIH will not further ramp down spending in anticipation
of a sequester. We will continue to operate cautiously pursuant to the law, as well as
general and NIH-specific policies for operating under a continuing resolution until a final
fiscal year 2013 budget is determined.
Moving on, in June of 2012, three working groups of the advisory committee to the NIH
director delivered their reports and recommendations after roughly a year of deliberations. NIH
is now moving forward in implementing most of these recommendations, and I want to now
briefly update you about each of these areas and each of these working groups.
So starting with the Diversity in Biomedical Research Workforce working group: This group
analyzed the NIH Intramural and Extramural research communities retention of underrepresented
minorities, persons with disabilities, and persons from disadvantaged backgrounds in
the biomedical research workforce. The working group proposed strategies to implement their
recommendations on improving diversity in the biomedical workforce, and NIH plans to
implement these recommendations. They include establishing the NIH Building Infrastructure
Leading to Diversity, or BUILD program, and the NIH Research Mentoring Network. Both programs
are intended to strengthen mentoring and career preparation. Each program will create a coordinating
and evaluation center to monitor outcomes and enhance fairness in the peer review process
through pilot interventions.
The Biomedical Research Workforce Working Group focused on developing a model for sustainable
and diverse U.S. biomedical research workforce able to inform decisions about training the
optimal number of people for the appropriate types of positions to advance science and
promote health. This workforce working group proposed several implementation strategies
and these are being implemented by NIH. These include elements aiming to establish a grant
program to encourage innovative approaches to biomedical training in institutions receiving
NIH funds; to improve training for graduate students and post docs; and to create an NIH
functional unit to assess the biomedical research workforce in an ongoing way. The timing and
details for all of these implementation steps are currently being worked out.
The third of the three working groups on data and informatics, also referred to as the Big
Data Working Group, is the one that NHGRI has been the most involved with. In fact,
council member Joe Mesrof [spelled phonetically] served on this working group, and a number
of us at NHGRI have been heavily involved in these discussions, so I thought I would
spend a few extra minutes providing additional details about this working group.
Now the report of this working group shown here is really quite good. And the recommendations
in this report fall into two broad categories related to administrative and on‑campus
NIH data on the one hand, and then scientific and biomedical data, more broadly, on the
other hand. There is now an implementation plan being pursued to deal with the challenges
of administrative data and on‑campus NIH data bundled into an initiative called Infrastructure
Plus, which aims to create an adaptive IT environment at NIH to sustain world-class
biomedical research. I can tell you, NHGRI is only indirectly involved in this effort,
and so I will not discuss this further.
For some scientific big data, NIH is acting on the recommendations of the working group
by implementing a three‑prong plan, all of which NHGRI is extensively involved with.
But before telling you about these new plans, I really want to stress a point made by the
working group in their report. The current biomedical big data problems that all of us
face are not limited to genomic data. Admittedly, genomics can be considered a poster child
for the big data problems, but there are many other data types, such as those shown here,
that currently are or will increasingly be contributing to the broader challenges in
biomedical research related to big data. So in implementing the recommendations of the
Data and Informatics Working Group, NIH aims to tackle the problem across all these data
types and others. So just because NHGRI is being asked to play a major role in leading
the implementation of the new programs, it does not mean that the solutions are going
to be limited to genomic data.
So in tackling the big data problem, Francis Collins recently announced the implementation
of the following three things. First, he has established a new NIH leadership position
called the associate director for Data Science, an individual who will report to the NIH director
and who will, in essence, be the NIH's programmatic leader in data science, broadly defined. On
an interim basis, he asked me to be the acting associate director for Data Science, but I
can tell you, at the same time, I'm also co‑chairing the search committee that aims to recruit
a world‑class data scientist in the position so that someone other than me can be doing
this. And that search, I can tell you, will commence in the coming weeks, and I'm sure
I'll be in contact with some of you to help identify suitable candidates and encourage
them to apply.
Second, Francis has created a new internal NIH governing or oversight body for things
related to data science and big data called the Scientific Data Council. It's an internal
group, but this group will be chaired by the associate director for Data Science. They'll
have a number of important responsibilities, including overseeing all aspects of the third
element of this program, and that's a new trans-NIH initiative called Big Data to Knowledge,
or BD2K.
Now, BD2K is a major trans‑NIH initiative that aims to address an NIH imperative and
a key road block in biomedical research related to big data and data science. It is designed
to be extremely ambitious. It's aimed to be transformational, catalytic, and synergistic,
and I really would regard its overarching goal is something along the lines of, by the
end of this decade, to enable a quantum leap in the ability of the biomedical research
enterprise to maximize the value of the growing volume and complexity of biomedical big data.
Few other details, BD2K is initially being organized for seven years through fiscal year
2020. Active planning for BD2K will take place throughout the this fiscal year with a launching
of some of the initial elements starting in fiscal year 2014, which is only eight months
away at this point. At a time when budgets are tight, the collective NIH leadership was
able to identify both common fund monies and institute and center funds to allow the initiative
to grow to just over $100 million by fiscal year 2016. Mark Guyer is leading a trans‑NIH
group of program directors involved in implementing BD2K, and we expect that NHGRI will end up
leading some of the elements of the program, and as such, will likely be bringing BD2K
components to this council for your input.
So for that reason, let me just very briefly list for you the four major programmatic areas
of BD2K, with the promise that at future council meetings, we will for certain be telling you
about each of these important areas in greater detail. And they are as follows. There'll
be four components to this. One, revolving around facilitating broad use of biomedical
big data. A second, for developing and disseminating analysis methods and software for biomedical
big data. One focused on enhancing training for biomedical big data. And then one for
establishing centers of excellence for biomedical big data. And again, I'm just putting these
out as teasers. We will be coming back and discussing these in detail, I'm quite sure,
in future council meetings.
So, those were the three working group reports for the advisory committee, the NIH director.
So moving on, last week, it was announced that Subra Suresh, the director of the U.S.
National Science Foundation, will be leaving the agency in July to take up the post of
president of Carnegie Mellon University. He joined the NSF in October of 2010, coming
from the Massachusetts Institute of Technology where he was Dean of Engineering.
And that is the end of my NIH updates, so let me move on to general genomics updates.
Starting on a sad note, the genomics community, and all of us at NHGRI, were shocked and saddened
to learn of the sudden death of our good friend and colleague, David ***, last month. David
was truly a Renaissance scientist. He was a geneticist, a pediatrician, a technology
pioneer, and an entrepreneur. His contributions to genetics and genomics were many, and were
remarkable. He was formally professor of Genetics in Pediatrics at Stanford University and founder
of Perlegen Sciences. In 2008, he joined Pfizer to shepherd development at that company's
efforts in genomic medicine. Of particular relevance to NHGRI, he served on the program
advisory committee of the Human Genome Project in the early 1990s and was a major participant
of the Human Genome Project.
Another good friend and loyal supporter of NHGRI and NIH, Senator Arlen Specter, passed
away this past October at age 82 from complications of cancer. The former Senator from Pennsylvania
was a tireless proponent of NIH and its mission, and together with Senator Tom Harkin, Specter
led an effort to double the NIH budget from 1998 to 2003, and he later helped secure $10
billion in stimulus funding for NIH within the 2009 Recovery Act. He was also a proponent
of Human Embryonic Stem Cell Research and helped to create the Cures Acceleration Network.
A well‑known figure within the genomics community, Lee Hood, has been awarded the
National Medal of Science. This medal is the highest honor bestowed by the U.S. government
to scientists, engineers, and inventors. These accomplishments include the development of
various automated technologies, including the first automated fluorescent-based DNA
sequencer that enabled the mapping and sequencing in the human genome, and, in many ways, revolutionized
the field of genomics. Congratulations, Lee.
The 62nd Annual Meeting of the American Society of Human Genetics convened in San Francisco
in early November. At the meeting, there were major awards given that are of particular
relevance for NHGRI. Francis Collins received the 2012 Victor A. McKusick Leadership Award,
which recognizes individuals whose professional achievements have fostered and enriched the
development of human genetics. And Jay Shendure, an NHGRI grantee, was awarded the 2012 Curt
Stern Award which recognizing outstanding scientific achievements occurring in the last
decade.
Another NHGRI grantee, Stephen Quake, was recently awarded the 2013 Nakasone Award for
his work developing technologies in biophysics, biological automation, genome analysis, and
personalized medicine. This award is given by the Human Frontier Science Program Organization.
Another good friend of NHGRI and former chair of our Intramural Research Program's Board
of Scientific Counselors, Hal Dietz, was awarded the 2012 Taubman Prize for Excellence in Translational
Medical Science. Hal's productive career study in Marfan, Loeys-Dietz, and other connective
tissue syndromes has led to a clinical trial using the blood pressure drug Losartan for
treating Marfan syndrome patients at risk for aortic aneurism.
Speaking of our Intramural Research Program, one of our intramural branch chiefs, Elaine
Ostrander, recently received a 2013 Genetics Society of America Medal. This award recognizes
elegant and highly meaningful contributions to genetics within the previous 15 years of
their career. In addition to her work on human prostate and breast cancer, Elaine is known
throughout the scientific community as one of the world's foremost authorities on canine
genomics.
Another Genetics Society of America award, the 2013 Edward Novitski prize, was recently
given to Jonathan Pritchard, an NHGRI grantee. This award recognizes an extraordinary level
of creativity and intellectual ingenuity in solving a significant problem in genetics
research.
The Institute of Medicine recently announced their newly elected members. New members of
particular significance for NHGRI include Lynda Chin, a major participant of TCGA; Dan
Kastner, the Institute's Scientific Director; and Steve Quake, who I just mentioned a few
slides ago. And the same holds true for recently elected fellows of AAAS, with the individuals
listed here, having notable ties to NHGRI: Michael Brent, Susan Celniker, Joe Ecker on
our council, Steve Henikoff, Kathy Hudson, Lynn Jorde, Rob Knight, Charles Lee, Elaine
Ostrander who I just mentioned, Reed Pyeritz, Dan Roden, Jane Silverthorne, and John Stam.
So congratulations to all of them.
Now, after a lengthy search, the New York Genome Center has appointed physician scientist
Bob Darnell as its first president and scientific director. Bob is an outstanding researcher
and member of the Howard Hughes Medical Institute, and his expertise is in molecular biology,
internal medicine, and neurology. I've known Bob for a very long time. He was an MD/Ph.D.
student at Washington University, just a few years older than me. Actually, just a couple
years older than me in the program; actually was ‑‑ did his Ph.D. in one of the two
labs I did my Ph.D. on. And I've ‑‑ we've remained friends ever since. I think this
is a terrific addition, and I've already had one conversation with him, and I'm sure we'll
be hearing more from the New York Genome Center in the coming weeks and months.
Stanford University recently announced a launching of a new Genomics Research Center: The Stanford
Center for Computational, Evolutionary, and Human Genomics. Council Member Carlos Bustamante
is co‑director, along with Mark Feldman. The Center's focus will be at using expertise
and methods for sorting through, integrating, and analyzing large scale datasets.
The Office for Human Research Protections, OHRP, recently appointed four new members
of the Secretary's Advisory Committee on Human Research Protections. Two of those individuals
are well-known to NHGRI: Jeff Bodkin, who's actually the chair designate; and former council
member, but now ad-hoc council member today, Pilar Ossorio. And the other two members are
Thomas Eisenberg [spelled phonetically] and Owen Garrett [spelled phonetically].
In some breaking news announced just last week, Joe McInerney will soon become the new
executive vice president of the American Society of Human Genetics. Joe was the director of
the National Coalition for Health Professional Education in genetics, or NCHPEG, for 10 years,
until 2010. He's also been active in NHGRI's ELSI Program over the years. Joe has a master's
degree in genetic counseling; has been a public proponent for the teaching of evolution for
many years. We look forward to working with Joe when he assumes his new leadership position
with ASHG.
Well, last month, Gynrek et al published a paper in science describing a method to deduce
surnames and then identify individuals in the well‑studied CEPH population, using
data about short tandem repeats on the Y chromosome in various publicly accessible Internet resources.
Note that the identification of study subjects was possible without having a matching DNA
sample and with access only to publicly accessible datasets. Well, the authors contacted NHGRI
and NIGMS about their findings prior to publication so that we could explore possible options
to mitigate the privacy vulnerabilities and the research data. As a precaution, age information
for the CEPH participants, which previously was available through the public pages within
NIGMS's cell line repository at the Coriell Institute and played a role in the participant
identification, was moved out of open access. The PI for the CEPH study and IRB officials
of the University of Utah were contacted to alert them to the new findings in advance
of publication. NHGRI also discussed the matter with one of our genealogy ‑‑ one of the
genealogy resources used in the work that was used to identify the surnames.
Well, to highlight the broader policy context of the reported work, NHGRI staff and Judith
Greenberg, who's the NIGMS acting director, co‑authored and accompanied policy form
in the same issue of science. That paper calls on the research committee to engage in a renewed
and open discussion about how to balance protection of research participants with the societal
benefits of broad data sharing, especially in the context of the increasing opportunities
to connect research and non-research information in the public domain.
The American College of Medical Genetics and Genomics released a position statement last
November calling for the public disclosure of clinical variant data that laboratories
collate from genetic testing. The statement describes the College's concerns about how
gene patent monopolies are allowing some laboratories to develop proprietary databases that facilitate
the interpretation of individual variants. In the statement, they explained that ACMG
believes that monopolistic practices that limit a given genetic test to a single laboratory
are inconsistent with their policy goals of broadly accessible and affordable genetic
test.
Meanwhile, the lawsuit over Myriad's BRCA1 patents and possibly gene patents all together
maybe heading towards a final resolution in 2013 with a recent announcement by the U.S.
Supreme Court that they will hear the case later this year. As you may recall, the case
began in 2009 when several pathology societies, as well as several clinical pathologists and
breast cancer patients, challenged the U.S. Patent and Trademark office, Myriad Genetics,
and the directors of the University of Utah Research Foundation over the patent ability
of Myriad's BRCA1- and BRCA2-related patents. Previously, a federal district court ruled
in favor of the plaintiffs, finding that Myriad's claims to the BRCA1 genes were not patent-eligible.
But this decision was reversed by the Court of Appeals for the Federal Circuit. The case
was appealed to the Supreme Court. In March of 2012, the Supreme Court asked the Court
of Appeals to reconsider the case in light of another long-running biomedical patent
dispute between Prometheus and Mayo Laboratories, but the Court of Appeals came to the same
conclusion as before. The Supreme Court recently announced that they will hear the case this
coming year, specifically in the question of whether or not human genes are patentable
subject matter. The Supreme Court's ruling in this case will set a binding precedent
for the lower courts.
In other legal battles, you may also recall that just over two years ago, NIH was blocked
from funding any human embryonic stem cell research as a result of a court case brought
by Drs. James Sherley and Theresa Deisher against Secretary Sebelius, DHHS, and NIH.
The injunction against allowing NIH to fund embryonic stem cell research was lifted by
the Appeals Court, and Judge Royce Lamberth found in favor of the NIH in July 2011. In
late August of 2012, the Court of Appeals considered the case and also ruled in favor
of NIH. Now I'm pleased to report that on January 7th, the Supreme Court announced that
they would not consider a final appeal from these two doctors bringing finality to this
case, and, thus, this case to a close.
Well, in addition to federal laws, individual states pass laws that affect genomics research
or have implications for genomic medicine. Some years ago, NHGRI created a database for
tracking legislation at the state level on policy topics such as genetic discrimination
by employers or health insurance providers. Over the years, the list of topics tracked
has been expanded to include issues such as privacy, informed consent and most recently,
the use of residual newborn screening specimens. We've now updated the database to include
all new statutes and bills from the last 2 years and added a table giving an up‑to‑date
snapshot about the number of states with laws on each topics. And this database is accessible
at our website, genome.gov.
Last month, the Department of Health and Human Services issued a final rule implementing
Section 105 of the Genetic Information Non‑Discrimination Act, or GINA. This final rule amends the privacy
rule of the Health Insurance Portability Accountability Act, or HIPAA, to clarify that genetic information
is health information. It also prohibits the use or disclosure of genetic information for
underwriting purposes. Consistent with existing HIPAA regulations, the final rule covers a
variety of health insurance types, both public and private, including group health plans,
insurers of health -- issuers of health insurance, Medicare supplemental policies, as well as
military and veterans health care programs. The final rule becomes effective in March,
and NHGRI continues to monitor genome-related issues through contact with the agencies responsible
for its implementation.
As you may recall, the Presidential Commission for the Study of Bioethical Issues has been
considering bioethics issues raised by advances in human genome sequencing. The commission
released its fourth report, "Privacy and Progress in Whole Genome Sequencing" in October, gathering
its information through a request for information, a survey of federal agencies, and a series
of public meetings. In its report, that commission provided 12 recommendations to ensure privacy
and security of whole genome sequencing data and information. The recommendations are intended
to support privacy protections across three identified facets of responsibility: the conduct
of genomic data users, the security of the systems employed to manage genomic data, and
the policy frameworks established to oversee access to a new sub-genomic information. The
majority of the report's recommendations are directed towards research and clinical activities,
but there is some discussion relevant to direct consumer companies and other private sector
entities. Upon reviews of the report, we believe that NIH and NHGRI policies are consistent
with commission's recommendations. The most recent meeting of the commission in January
-- they announced that they'll be taking up the issue of incidental findings in biomedical
research in a future report.
The European Science Foundation, a non‑governmental organization fostering scientific collaboration
across Europe, recently issued a new report on personalized medicine entitled, "Personalized
Medicine for the European Citizen." It observes that Europe needs to, quote, "Gain a clear
understanding of what is needed to fulfill the promise of personalized medicine and begin
to lay the foundations now that will allow us to benefit in the future." The report examines
the key issues affecting the development and implementation of personalized medicine and
provides a large number of recommendations for maximizing its potential. A meeting was
held in Brussels at the end of January to discuss the report and how its recommendations
can be implemented.
The Department of Energy's Joint Genome Institute held a Strategic Planning Workshop last spring,
and then more recently published this report. The major themes of the workshop of the report
included continued and increasing large-scale genome sequencing, functional and structural
annotation, improved bioinformatics methods, capacity to synthesize DNA, automation of
biological experiments, and organization of scientific communities.
Back over to the U.K. The U.K.'s Natural Health Service, NHS, recently announced an initiative
that aims to sequence the genomes of as many as 100,000 cancer patients. The U.K. government
has earmarked £100 million pounds to stimulate DNA sequencing for cancer and rare inherited
diseases, to train genetic scientists and health care workers to harness genomic sequencing
technologies, and to build the NHS data infrastructure for this. They hope to solidify their plans
for this by April of 2014.
NHGRI continues to feature a Genome Advance of the Month, on our website, genome.gov.
Publications that were featured since the last council meeting describe whole genome
sequencing used to track an infectious agent's transmission path; ENCODE's efforts to decipher
functional elements in the human genome; genes and weight: the potential of genomics to improve
our diet ‑‑ our diets; and single cell genome sequencing.
A number of genomics stories appeared in the news in recent months. For starters, ENCODE
was named as one of the runner‑ups of science's Top 10 Breakthroughs in 2012. And earlier
this year, the Wall Street Journal published a piece highlighting six medical innovations
soon to transform the treatment of disease. Three of the six innovations featured genetics
and genomics. Specifically, number two was the use of genome sequencing for routine medical
check-ups. Number three, was pharmacogenomics for cancer treatment. And number six was gene
therapy.
Similarly impressive for genomics, making both me and NHGRI incredibly proud, was Time
magazine's list of the Top 10 Medical Breakthroughs in 2012. Not one, not two, not three, not
four, but five of the Top 10 Breakthroughs on the list had genomics and NHGRI's fingerprints
all over them. Number eight was about decoding childhood tumors and the efforts of the Pediatric
Cancer Genome Project being carried out by St. Jude's and Washington University. Number
seven was about speeding DNA-based diagnostics for newborns using next-gen genome sequencing
methods. Number six was about TCGA's breast cancer studies. Number two, was about NIH's
Human Microbiome Project. And number one was about NHGRI's very own ENCODE projects and
its impressive set of publications last year. Pretty impressive: five out of 10 last year.
And finally, genomics in the news, there have been a number of organisms whose genome sequences
have been reported since the last council meeting, and these stories were also covered
in the news at various levels. They included barley, camel, chickpea, cone jelly, fly catcher,
goat, oyster and its 28,000 genes, panda, the pig, watermelon, and wheat. And then,
of course, there was that disturbing story that got considerable media attention about
sequencing Sasquatch's genome. But NHGRI does not officially endorse that claim, pending
further verification.
[laughter]
So, moving on to NHGRI's Extramural Research Program. The large-scale genome sequencing
and analysis centers are undertaking numerous projects, mostly related to complex disease
and cancer. In the most recent grant year, the three centers produced over 300 terabytes
of sequence, the equivalent of approximately 3,000 high coverage whole human genome sequences
or 41,000 whole exome sequences. At the centers, there are over 120 ongoing projects focused
on cancer, complex disease, rare diseases, and comparative sequencing. Meanwhile, these
groups together had over 20 papers either published or impressed this past quarter alone.
And into the some of the more specific projects. For the 1,000 Genomes Project, the Phase 1
paper was published in Nature late last year. And 1,000 Genomes consortium meeting was held
prior to the 2012 ASAG annual meeting to discuss the last phase of the project and future plans.
And then 1,000 Genomes Tutorial was held at the ASAG meeting itself with over 200 attendees.
There were many, many presentations and posters that were also featured, 1,000 Genomes data
at the ASAG meeting.
Phrase 3 sequencing--
Intercom Speaker: Please pardon the interruption. Your conference
contains less than three participants at this time. If you would like to continue, press
*1 now, or the conference will be terminated.
Male Speaker: Should we kill that?
Male Speaker: Yes.
Eric Green: Phase 3 sequencing, which will involve more
than 2,500 samples, will be complete by March of this year, and to discuss analyses, the
Phase 3 Data Analysis Group meeting will be held in May prior to the Cold Spring Harbor
Biology of Genomes meeting.
Moving on to The Cancer Genome Atlas. The Cancer Genome Atlas held a series of meetings
in November, starting with the second annual two‑day public scientific symposium that
was filled to its 500 person capacity. TCGA continues to generate and release results
at a rapid pace with findings coming not only from the TCGA network, but increasingly from
a large community of TCGA data users. The symposium was a great forum for shaking these
findings and for the user community to interact with TCGA investigators. Presentations from
this symposium are available as a video archive on genome.gov via our Genome TV channel of
YouTube.
At the end of the meeting, or end of that week, there was a joint NCI/NHGRI Strategic
Planning meeting to begin prioritizing areas of research that will follow and leverage
TCGA and similar large cancer genomics efforts. Participants in this meeting included Hal
Varmus, TCGA staff from both NCI and NHGRI, acting directors of NCI Center for Cancer
Genomics, TCGA PIs, and members of this council, the NCI board, and various ad-hoc experts.
The meeting produced a draft list of highest priorities goals, which still need some discussion.
One conclusion was that NCI and NHGRI need to continue to work together to push innovation
and research in cancer genomics beyond TCGA, and NCI and NHGRI staff are now working to
plan the next generation of initiatives.
Now Brad Ozenberger will be given a larger TCGA update later in this council meeting,
but I wanted to briefly note a few TCGA highlights. Since the last council meeting, a major TCGA
paper on breast cancer was published in "Nature," and TCGA currently has three additional papers
submitted and under review on renal clear cell carcinoma and endometrial carcinoma,
and on acute myeloid leukemia.
This Kaplan-Meier survival graph is a small teaser of some of the important results coming
out of the TCGA projects. It shows survival of individuals with endometrial tumors of
four different molecular types based on specific genomic hallmarks. Unexpectedly, those containing
mutations in the POLE gene, seen in the blue line, are completely progression-free. Ten
percent of the endometrial tumors have a POLE mutation, and in this TCGA study, all of those
patients remain disease-free for years following surgery. So POLE thus seems to be an important
new genetic marker for oncologists to consider in therapeutic decisions.
Our three centers for Mendelian Genomics have had a productive year one in terms of disease
gene discovery. Specifically, over 6,000 whole exome sequences have been generated for studying
over a 150 rare inherited diseases. This has resulted in the discovery of the genes from
more than 20 diseases, and roughly a dozen manuscripts have been published or accepted
for publication already.
In terms of outreach and coordination, these centers are expected to disseminate methodologies
and genomic data, and coordinate with the rare Disease Gene Discovery Project Worldwide.
List of phenotypes are being studied by the centers of publicly posted and updated quarterly.
Genomic data are released publicly at multiple levels, from the list of candidate genes and
disease genes to the sequence data via ‑‑ either via open access or via controlled access at
dbGaP.
The International Rare Diseases Research Consortium aims to deliver by 2020 diagnostic tests for
most rare diseases and 200 new therapies for rare diseases. Jeff Schloss now represents
NHGRI on the executive committee. Our centers mainly organized and participate in the diagnostic
and sequencing scientific committee of this new consortium. And among the center's activities
was the organization of a well-received session on Mendelian Genomics at the 2012 ASAG annual
meeting.
Moving on to the next component of our genome sequencing program, the Clinical Sequencing
Exploratory Research Program, or CSER, had a productive first year. All CSER projects
are now recruiting patients, with several already starting to return results to participants.
CSER working groups are currently preparing manuscripts on a range of topics, including
those focused on variant action ability and sequencing standards for clinical use.
As you may have noticed, our new capabilities to understand our genetic future has entered
the popular press. Time Magazine featured an article in December on the difficult decisions
associated with having access to one's own genomic data and some of the tough decisions
beginning to confront patients, parents, and doctors. And this article featured four of
the six funded CSER groups.
As a priority area for NHGRI, the CSER RFA was reissued and applications were reviewed
in January. Again, we had a large number of meritorious applications showing the substantial
activity already underway or being initiated in this area. An RFA for a Coordination Center
which will support the CSER program and the return of results consortium was also issued,
and this center will be important for the integration of CSER efforts with related NHGRI
programs and dissemination of best practices.
The last component of our genome sequencing program, the genome sequencing informatics
tools, or GS-IT program, aims to democratize access to sequence analysis for a broad community
of users outside of large centers. This program provides researcher-friendly sequence analysis
tools from the combined efforts of six projects which cover a wide range of sequence analysis
tasks. Together, the projects form the iSeq Tools Network. An iSeq Tools Portal grant
supplement has been funded to build a program-wide interface to help users seeking tools to analyze
their sequence data. And the portal will use innovative visual strategies and best design
practices to simplify sequence analysis and enable users to develop their own analysis
workflows with GS-IT tools.
Moving on, then, in terms of our DNA Sequencing Technology Development Program, two commercial
vendors released instruments last year. By later this year, these are anticipated to
be able to produce high quality sequences for a whole human genome, perhaps within a
day, as new kits and flow cells are released. New grants were awarded as part of our revolutionary
sequencing technology program. Approaches include solid state nanopores, hybrid between
nanopore with a specific biosystem system, faster electronic measurements for nanopores,
novel electronic detection of sequencing by synthesis and sequencing by hybridization
in microfluidic format.
Our program's annual grantee meeting will be held in San Diego later this spring, and
this will occur back-to-back with a public meeting on new sequencing technologies on
May 1st and 2nd.
Moving on to ENCODE. A tutorial workshop was held at the 2012 ASAG Annual Meeting that
provided information about both the ENCODE project and also the Common Fund Epigenomics
Program. The focus of the tutorial was how to use data from these resources to understand
the role of genetic variation in human disease. The tutorial was attended by about 200 people,
and presentations from that workshop are also available on our Genome TV channel of YouTube.
ENCODE began its third phase last September and grant awards have been made to seven production
centers, a data analysis center, a data coordination center, and some six computational analysis
groups, and all this was in addition to the eleven technology development groups funded
earlier. An organizational meeting for the ENCODE production PIs was held in December
of 2012 to coordinate data production to establish new working groups. And ENCODE is planning
a consortium meeting in May of 2013. The data production centers, data analysis and coordination
centers, computational analysis groups, and technology development groups will present
updates on their projects. We'll begin to develop coordinated analysis plans and finalize
consortium goals and policies.
Among the important ENCODE data being ‑‑ data analyses being pursued, there are some cross-species
papers that are being planned with manuscripts likely to be submitted early this spring.
modENCODE is conducting comparisons of fly, worm, and human data. One main paper will
examine chromatin; the second will examine the transcription factor binding; and a third
paper will compare the transcriptomes of these organisms. Mouse ENCODE is working on a single
paper comparing functional genomic elements in mouse and humans.
The annual CEGS grantee meeting was held this past October at the University of North Carolina.
Nine centers shared their latest results through talks, posters, and lots of good conversation.
The CEGS program solicitation expired this past year. These have a three-year lifespan,
and later today we will discuss renewing this program. In preparation for that discussion,
you'll hear about the results of two CEGS projects that are ending from two of our council
members. And then in the closed session, we'll be considering a new set of applications for
possible funding.
You may recall that NHGRI has been sponsoring a serious of genomic medicine symposia involving
and inviting representatives of the academic medical centers and integrated health systems
currently engaged in or hoping to become engaged in the active application of genomic medicine
to clinical practice. This is a key activity led by council's genomic medicine working
group. A manuscript describing an implementation road map for bringing genomic medicine to
the clinic was accepted for publication and genetics in medicine and is now available
through Nature's Advance Online Publication service.
The limitation [spelled phonetically] road map is based on the outcomes of the Genomic
Medicine One Consortium, the first meeting of its kind, which took place in June of 2011.
Meanwhile, as one of its informal roles, council's Genomic Medicine Working Group has started
to compile high profile accomplishments in genomic medicine that illustrate the utility
of genomics for clinical care. And we're cataloging these on the Genomic Medicine Working Group
webpage on genome.gov as a resource.
So just give you some examples, in June, Jay Shendure's group at University of Washington
used whole genome sequencing of DNA isolated from internal plasma to sequence the genome
of an unborn fetus, demonstrating the ability to do non‑invasive genetic screening of
a child before birth. Here at the NIH, Julie Segre's group used genome sequencing group
to track an outbreak of an antibiotic-resistant strain of Klebsiella pneumoniae at the NIH
Clinical Center, allowing them to gain insights into its modes of transmission. Steven Kingsmore's
group at Children's Mercy Hospital of Kansas City created a system that could produce whole
genome sequencing results for diagnosing genetic diseases in NICU patients in just 50 hours.
And in October, investigators at Harvard show that early stage colorectal cancer patients
with mutations in the PIK3CA gene could live longer by taking aspirin after their diagnosis.
The Genetic Medicine Working Group held its fourth genomic medicine meeting two weeks
ago in Dallas. The main goals of the meeting were to work with professional societies to
identify ongoing efforts and current needs in physician education in genomics and understanding
the processes of guideline development in the use of genomics in promoting collaborations
among the societies in physician education and in guideline development.
Representatives from 10 professional societies across a range of disciplines, as well as
representatives from two regulatory bodies, specifically the Accreditation Council for
Graduate Medical Education and the Accreditation Council for Continuing Medical Education,
attended this meeting, and the meeting was extremely productive. The major outcomes emerging
from the media including consensus to convene a professional society's coordinating committee.
And we're working for bring this group together in the next month, and among other activities,
the coordinating committee would collect currently approaches and develop and disseminate societies
best practices for pharmacogenomics, directed consumer testing, genome sequencing, and incidental
findings. And videos of the meeting will be available shortly on genome.gov. And meanwhile,
the Genomic Medicine V meeting is scheduled to take place in late May in Bethesda.
One of the outcomes of one of the earlier genomic medicine meetings was the realization
that we needed to better understand the issues surrounding health care reimbursement as it
relates to clinical genomics advances. And an example of a good collaboration between
different parts of NHGRI, staff from the Division of Policy Communication Education took the
lead in organizing a workshop focusing on reimbursement models to promote evidence generation
and innovation for genomic tests. This meeting took place at NIH in October, and, importantly,
was held in partnership with the Center for Medical Technology Policy, or CMTP. In attendance
were members of the Genomic Medicine Working Group and representatives from several stakeholder
communities, including government, payers, manufacturers of genetic diagnostic tests,
and academia.
The attendees discussed the concern that a lack of evidence of clinical utility leads
to genomic-based tests not being covered by health insurance. And the groups discussed
ways in which the problem can be overcome by coupling the coverage of tests with ongoing
research as to their utility. The meeting identified a number of action items including
the analysis of the legal and policy issues affecting data sharing between stakeholders,
such as a payers and test developers, and research on physician practices related to
the ordering of tests. In a summary, the meeting can be accessed on genome.gov, and both NHGRI
and CMTP staff are now working to pursue action items coming out of that meeting.
Well, because genome sequencing is increasingly being used to diagnose and develop potential
treatments for human disease, we sponsored a workshop immediately after our September
council meeting to address the challenges involved in determining whether a variant
is causal in a specific disease. The goal of the workshop was to develop guidelines
for assessing the evidence implicating sequence variants or genes as causal in a specific
disease. In effort by NHGRI's communication group to provide live video of as many NHGRI
workshops as is feasible, the workshop was the first to be streamed online, and the archive
is also available on genome.gov. And a consensus manuscript coming out of the workshop is in
preparation and hopefully will be published out later this year.
Moving on to the eMERGE Network. A key goal of the eMERGE Network in its current phase
is to explore the best avenues to incorporate genetic variants into electronic medical records
for use in clinical care among diverse populations. The eMERGE Network has had a significant impact
on the scientific community, and one of indicators is the number of the publications coming out
of the program. So far, eMERGE has published 23 papers as a network and 64 papers have
come out of individual studies. And highlighted in this slide, demonstrating sort of how advances
in genomic studies of clinical disease and traits benefit from the linkage of electronic
medical records to biorepository samples.
As you may recall, the Genomics and Randomized Trials NETwork, or GARNET, was started in
2009 to identify genetic variance associated with response to treatments in three randomized
clinical ‑‑ randomized controlled clinical trials as listed here. The program, which
was comprised of a series of genome‑wide association studies, held its final steering
committee meeting in December of 2012, and grants are in their last year of funding.
So far, GARNET is associated with 30 publications at various stages of maturation, and more
are expected as the program finishes its final analysis.
Finally, turning to NHGRI's ELSI Research Program, this past fall, NHGRI established
a Genomics and Society Working Group as a working group of this council. The mission
of this working group is to provide advice on short and long-term range planning and
priority setting for genomics in society activities at the Institute, with particular emphasis
on the ELSI Research Program. The first in-person meeting of the working group will be held
in April.
The new Centers of Excellence in ELSI Research, or CEER, specialized centers, P-50 in exploratory
research, P-20 applications were reviewed in November, and will be discussed later in
the closed session. Finally, the return of results -- the Return of Research Results
Consortium and the Clinical Sequencing Exploratory Research program will hold their second joint
meeting in May. This meeting will bring together investigators from the CSER program as well
as R01, R21, and other independent projects funded by the ELSI Research Program related
to return of results.
And those are the highlights from the extramural research program, so now, turning our attention
to the NIH Common Fund.
Starting with the Molecular Libraries Program, or MLP, which offers researchers access to
screening capacity needed to identify small molecules that can be optimized as chemical
probes to study the function of gene cells and biochemical pathways. Chemical probes
may also be used to validate new drug targets. Now, remember that MLP began in 2004 with
Common Fund support, and it'll be one of the first large programs to transition off of
Common Fund support when it ends in May of 2014.
Several strategies are being used to transition MLP initiatives off of Common Fund support.
One strategy is to have NIH institutes and centers support ongoing initiatives, for example,
NCATS is now funding the NIH Chemical Genomic Center, NCGC, which was originally an MLP
production center. Initiatives that have achieved their objectives, like the pilot-scale libraries
initiative, will be closed out, and private sector support will be sought for some MLP
initiatives, like the molecular imaging and contrast agent database.
Other MLP resources remain important so other sources will support for their maintenance
have been identified. For example, the Small Molecule Repository is a compound bank containing
highly diverse compound structures ideal for screening in the search for chemical probes.
This repository has grown over the years to become a valuable resource, now containing
over 380,000 compounds. Plans are for this resource to be partially supported by NCATS.
NIH is also exploring ways to provide compounds to investigators at cost to help support the
repository.
MLP data-sharing policies call for the deposition of all assay and chemical structure data,
both positive and negative results in the PubChem database, and this database will be
maintained by NCBI after the program ends. NCATS is managing and hosting the MLP assay
guidance manual and high-throughput screening assay guidance criteria. Reports on the chemical
probes discovered by MLP are available on the NCBI bookshelf. These probe reports are
also listed as citations in PubMed. And MLP is developing a bioassay research database
that will provide expanded biological queries of chemical biology data. Plans are for NCATS
to maintain the database after Common Fund support ends.
Moving on to another major Common Fund project, the Human Microbiome Project. Recall that
the initial HMP effort is in its last year of funding. The Common Fund is proceeding
with a smaller next phase for HMP, known as HMP2, with the aim of deciphering the role
of the microbiome in human health through the integration of several microbiome multi-omic
[spelled phonetically] datasets obtained from human donors.
Applications for HMP2 were received in response to an RFA for HMP2. The Common Fund will provide
$5 million per year for three years for a total of $15 million dollars, and funding
will commence this fiscal year. A trans-NIH Microbiome Working Group is now in place and
has 64 members from 16 institutes and centers. This group will track and coordinate microbiome-related
funding opportunities across the NIH. These efforts will help prospective applicants identify
relevant funding opportunities and program staff in different institutes and centers.
And HMP will hold a major meeting in 2013 entitled "NIH Human Microbiome Science: Vision
for the Future." This meeting has been organized to provide an overview of cutting-edge work
in NIH-supported microbiome research, and to identify the obstacles to and opportunities
for progress in the emerging area -- in this emerging area of biomedical research.
Moving on to Knockout Mouse Phenotyping Project, KOMP2, the most significant event for KOMP2
since the September council meeting was the approval of a request to the Common Fund for
supplemental funds to support embryo phenotyping. There is significant interest in the community
about the identification and characterization of knockouts that are embryonic lethal. Because
this work is expensive, KOMP2 could only afford to confirm embryonic lethality by examining
embryos at embryonic day 12.5. This does not provide much granularity at this -- in this
broad class of mutations. For example, we cannot distinguish early pre-implantation
lethals from placental failures, or identify cardiac malformations or spina bifida.
So emerging high-resolution imaging technologies, like microcomputer tomography and optical
projection tomography, allow detailed examination of the embryos as early as embryonic day 8.5.
In a position paper summarizing a community meeting held in 2012 is now submitted, but
this manuscript describes the opportunities and rationale for such an effort, and this
served as the basis for a request we made to the Common Fund for additional resources,
and the Common Fund has now approved a supplement of $9.6 million over the next three years
to generate these data, and to store and disseminate these imaging datasets.
Moving on to the Genotype and Tissue Expression, or GTEx project, which aims to build human
gene expression and regulation in multiple tissues. The goal is to build valuable insights
into the mechanisms of gene regulation, and, in the future, its disease related perturbations.
Following its successful pilot, GTEx is about to begin its scale up phase with a goal of
studying 900 donors. Genotype data will be obtained on all donors, and RNA-seq analysis
will be performed on roughly 20,000 samples. The donors will eventually have their genomes
sequenced, and a pilot exome sequencing effort will begin soon.
A GTEx eQTL Browser and Data Portal are now live in an RFA, designed to enhance GTEx with
additional molecular assays, is currently open, with a receipt date of March 28th. And
you'll hear more about this and the rest of the GTEx program in an update later today.
Moving on to LINCS, the 2nd Annual LINCS Consortium Meeting was held this past November, and at
this meeting, the external scientific panel noted that LINCS has made good progress in
data generation and technology development and expressed excitement about data access
via the Cloud, and some of the inercative [spelled phonetically] visualizations that
are in beta release.
The major recommendations for the future included that LINCS explore reproducibility and variability
across replicates, and formally consider a role for the community in selecting new experimental
states. The redesigned lincsproject.org website, also launched in November, this website will
act as a central portal through which users can access LINC data and LINCS tools. And
then in March, this coming March, a LINCS data forum will be held in Boston; attendees
are invited to participate in discussions about the curation and management of large
datasets. Methods for integrating data from diverse sources, that's imaging data, biochemical,
gene expression data, as well as genomic data. And the role of standards for data annotation
and accessibility. Approaches to query browse and perform integrative data analyses with
LINCS and other data will also be showcased at this forum.
H3Africa, which provides funding directly to African institutions to support genomic
research, celebrate its official launch at its inaugural meeting in Addis Ababa, Ethiopia
this past October. The meeting included grantees delivering presentations on their proposed
research, and a press event to publicly announce their initial awards. The next two days were
devoted to a discussion of policies that will guide the consortium, and it also resulted
in the convening of an H3Africa Steering Committee composed of principal investigators and funders,
and also the creation of 10 working groups for the consortia. The next H3Africa Consortium
meeting will be held in Accra, Ghana, in May, back-to-back with the 2013 African Society
of Human Genetics meeting. And you'll be hearing more about H3Africa later today as well.
Last Common Fund update. Recall that the NIH Undiagnosed Diseases Program, or UDP, started
as an effort within the NIH intramural program, that has now transitioned to Common Fund support.
The planned expansion into a national UDP network will leverage the experience and resources
of the intramural program's UDP to initiate similar endeavors at five to seven extramural
centers across the country. An RFA for a Coordinating Center will serve as a resource to assist
in the creation, support, intersite communication and management of the new network, was issued
in November of 2012, and applications were received at the beginning of February, and
we anticipate funding a coordinating center later this year.
A program announcement was issued at the beginning of January to support gene function studies
in collaboration with the UDP. These studies will investigate the underlying genetics,
biochemistry, and pathophysiology of newly-diagnosed diseases identified within the UDP. Applications
for this program announcement are due later this month, and we anticipate issuing other
funding opportunities for gene function studies as the program evolves.
So, moving on now to our newly-created division of policy, communication, and education, just
a few updates here. Since December of 2011, NHGRI has collaborated with Suburban Hospital
in Bethesda and the Johns Hopkins University School of Medicine to hold a monthly seminar
covering topics in genomic medicine as part of Suburban Hospital's grand rounds. The series
is intended to educate healthcare professionals about the increasing role of genomics in clinical
care. The lecture series has been very well-received, and Suburban Hospital has asked us to extend
this series twice. Lectures have covered the intersection of genomics and breast cancer,
cardiovascular disease, Parkinson's disease, and auto-inflammatory diseases among others,
and the next phase of the series is being organized and will focus on genomics and oncology.
Each of the lectures has been attended by 80 to 100 practicing physicians, mostly internists
and medical sub-specialists, but in addition, and in order to reach a larger audience, all
of the talks are being videotaped and made available on the Genome TV channel of YouTube.
For over a decade, NHGRI's online talking glossary of genetic terms has been a favorite
tool on the genome.gov website for teachers and students. It features over 30 NHGRI experts
explaining roughly 250 genetic terms in lay language and in a conversational style. A
year ago, we released one of NHGRI's first mobile apps, in this case, for use of the
talking glossary on the iPhone. That app has been downloaded more than 10,000 times for
the Apple iStore. So, in January of this year, partly in response to input from teachers
and students, we released an iPad version of the talking glossary app. The iPad app
contains all the same features as the online version including 3-D animations and full
color illustrations, and both apps are available free at the Apple app store.
NHGRI's Jean Jenkins and NCI's Kathy Calzone spearheaded the publication of a 2013 Genomics
Special Issue of the Journal of Nursing Scholarship, which was released online on February 1st.
The articles are all now available. I actually co-authored the editorial "Relevance of Genomics
to Healthcare and Nursing Practice," which accompanied the 11 articles about genomics
of common health conditions. The paper closing the special issue, "A Blueprint for Genomics
Nursing Science" resulted from a joint effort with the National Institute of Nursing Research
and provides recommendation for nursing research in this area.
And finally, webinars with insights from authors involved with the special issue will be coming
soon and made available, again, on our GenomeTV channel on YouTube.
And last, but certainly not least, I always like to say a few things about accomplishments
of our intramural research program, and, as always, there were many, many recent highlights
from our intramural program since the last council meeting. Just to give you a flavor,
I'll list a few.
Bill Gahl's long-standing efforts in studying the lysosomal storage disorder, nephropathic
cystinosis, resulted in the FDA approval of the use of cysteamine, which dissolves painful
and damaging cystine crystals in patients' eyes. Daphne Bell had an impressive paper
published in Nature Genetics, where she described driver mutations in six newly-identified genes
that play a role in serous endometrial cancer, one of the most lethal forms of uterine cancer.
Andy Baxevanis's group sequenced and analyzed the genome of cone jelly recently published
in BMC Biology. KJ Myung's group reported in the Journal of Cell Biology how deficient
ATAD-5 results in stalled DNA replication to a buildup of proteins and replication factories,
a defect associated with cancer in mice. And Dan Kastner and collaborators report in Nature
Genetics the results of a GWAS analysis of Behcet's disease, which pointed to four important
regions in the genome known to play a role in immune function.
We're at the end, finally. I do want to give a personal thanks, first of all, to all the
various NHGRI staff. You should realize there's probably 40 -- or probably 50 to 60 people
involved in pulling together the hundred slides I just went through and all the information
associated with them, and needless to say, without a group effort across the Institute,
I could never give such a detailed director's report at each council meeting. And then,
of course, a special thanks to Kris Wetterstrand, who serves as the ringleader in coordinating
material development and directly provides to me the final PowerPoint product for refinement.
And thanks to Larry Thompson, Judy Wyatt, and the NHR web team for making my director's
report available as an electronic resource.
But before I turn this open to council, I do want to point out one other important historic
event happened since the last council meeting, and I don't know if people realize what today
is, one council member may know what today is, because today is the day that pitchers
and catchers report to spring training in baseball. We pay attention to these things,
especially diehard Cardinal fans. I have to point out, because we all care about greatness
at this council, the sad passing of "Stan the Man" Musial. As a diehard Cardinal fan,
I'm sure Rick Wilson shares the same view; it's a sad day for St. Louis when Stan the
Man passed away. This is shown here: Last year, he got the medal of freedom, the highest
honor given by the President of the United States, he got the medal of freedom before
he passed away. So, in any case, just wanted to point that out to commemorate the opening
of spring training of professional baseball.
Male Speaker: Tomorrow's a big day.
Eric Green: And tomorrow's a big day.
Male Speaker: Darwin's birthday.
Eric Green: And tomorrow's Darwin's birthday, and I didn't
have a slide for that because I figured I'd better not go over a 101 slides. Who did he
pitch for? Wait, how many MVP's did he get?
[laughter]
So, with that, I will close. Thank you for your attention. Happy to take questions. Jo.
Joanne Baughman: Yeah, I just wanted to clarify something,
that the British 100,000 genomes is about germ line sequencing, correct?
Eric Green: It might also be tumors.
Joanne Baughman: Well, that's what I was going to ask, is it
possible that they'll be, for the cancer patients' tumors bank, that could then also be?
Eric Green: So, I don't know the answer, I'm looking if
anybody in the back, any of my staff know any details. From the discussions I've had
with people, including the discussion Mark Iron [spelled phonetically] -- actually met
with Mark Walpark [spelled phonetically] recently when he was over here giving a talk at NIH,
I think they're in very early days of deciding. I mean, they're not even planning to release
a plan for this until 2014.
Joanne Baughman: I see.
Eric Green: So I think anything we hear are bits and pieces,
I don't know if I would take any of them as etched in stone. Bob.
Robert Nussbaum: Eric, I wonder if you could comment on whether
NHGRI has any official or quasi-official connection to the Million Bet [spelled phonetically]
Project and having input into that program.
Eric Green: I'm looking to Teri Manolio in case she wants
to step to a microphone; she doesn't have to. I can tell you that we have had, and maybe
Laura Rodriguez as well, because I know I've been involved in at least two, possibly three
meetings that when they've come and talked to us, and I've gone and attended at least
one of their meetings, and it's been mostly just discussion at this point. I think the
details -- I don't think that it's reached a point in details for us to figure out how
we might participate because I'm not sure -- it's not entirely clear to me exactly when
they're ready to go forward on some of the things that we might be involved with
Teri Manolio: And I might just comment that they are -- their
investigators are working with us in a merge to come to multiple merge meetings, and so
we have a collaboration established there. At the higher levels of the VA, it's a bit
more challenging as you might imagine in bureaucracy being what it is. Data sharing is a real problem
for the Veterans Administration, and without that, we really can't go forward in anything
formal.
Eric Green: That said, Bob, I mean, I think we've been
pretty good about inviting them to participate in things that we think would be relevant
to somehow try to make sure we stay connected to their efforts as they develop.
Robert Nussbaum: I'm on their Genome Medicine Advisory Board,
as is Cynthia Morton, and so if you'd like to have some input through those channels,
let me know.
Eric Green: Thank you. It is helpful for us to know, I
was not aware of that, but it's good to have that connection through our council, then.
Any other questions? Any other questions?
[end of transcript]