Well, good morning, everyone. Let me remind you that the open session, as Rudy said, of this council meeting is being webcast live and is now our routine. The open session of all of our council meetings are videotaped and also made available as a permanent archive on the web. And that includes videos of all the presentations and also various associated documents. And specifically for my director's report for anyone new to our council meeting, including people coming in remotely, I want to make you aware that there's an electronic resource associated with my director's report as analogous to a supplemental materials often associated with published papers. And you can access it at the convenient URL shown on the slide. And the slides that I'm actually showing in this director's report are also available electronically, both as a PDF and also as a PowerPoint file. And for slides that are associated with the specific documents or also pointing to relevant websites, there is a document number indicated on the bottom right of the slide, which then references the materials that you can access on this website. In addition to the video archive I mentioned earlier, this web page itself and all linked documents will be permanently archived on NHGRI's website, genome.gov, as a permanent historic archive. There'll be multiple other presentations during the open session of this council meeting. And my director's report is going to be tailored around those presentations, and I won't be going into any detail those topics that others are going to cover. Following my director's report will have a presentation by Richard Nakamura, who is the recently appointed director of the NIH Center for Scientific Review. Later today, Council Member Bob Nussbaum will present the recent recommendations issued by the American College of Medical Genetics and Genomics, ACMG, regarding the reporting of incidental findings. And we will then hear reports from two recent NHGRI meetings. Council Member Pamela Sankar will discuss the first meeting of the Genomics and Society Working Group, and Betty Graham will discuss a recent workshop about NHGRI's training and career development programs. We will then have one program update and one concept clearance from NHGRI staff members. Adam Felsenfeld will give an update about the genome sequencing program with an emphasis on a strategic proposal for that program that's called Disease 2020. And Lisa Brooks will then present a concept clearance currently entitled interpreting variants and non-coding regions of the genome. For the rest of my director's report, I'll cover the seven areas that are listed here. These areas I found to provide a very good framework for reviewing the relevant topics. And we will start with some general NHGRI updates. Believing that it's always nice to start a meeting with a feel-good topic, April 14th, 2003 marked the 10th anniversary of the completion of the Human Genome Project. This milestone was met with some excellent press coverage, including an interview with yours truly in the New York Times, but also other coverage, including stories in the Huffington Post, the Milwaukee Journal Sentinel, NBC News Online, Health Day, and the San Francisco Chronicle. The 10th anniversary of the Human Genome Project did not go unnoticed by Congress on DNA Day, April 25th, Congresswoman Louise Slaughter of New York and Congressman Michael Burgess of Texas to gather with some of their house colleagues, introduced House Resolution 180, recognizing the 10th anniversary of the completion of the Human Genome Project, and the resolution praised the sequence of the Human Genome as one of the most significant scientific accomplishments of the past 100 years, and recognized the ongoing public education efforts in genomics. As you may recall, to commemorate the 10th anniversary of the Human Genome Project, NHGRI held a series of paired seminars beginning in February and also a day-long symposium last month. The last of the pair seminars was held on March 6th, which featured Carolyn Lehrman and Alexandra Shields, and a pair of talks together entitled Translating Pharmacogenetics Research to Practice, the case example of smoking cessation. Then on April 25th, DNA Day 2013, NHGRI held a day-long symposium on the NIH campus with participating speakers listed on the right side of this poster. On the all-star cast included council members David Kingsley and David Williams, as well as Sarah Tishkoff, Claire Frazier, Jeff Botkin, Kevin Davies, Nancy Cox, Ewan Burney, Levi Garroway, Dan Roden, David Botstein, and Frances Collins. It really was a truly outstanding day. And for those of you who were not there in person, all of these events, both the all-day symposium and also the paired seminars I told you about earlier, were all videotaped and are now all available on the Genome TV channel of YouTube, one designated specifically for all these celebratory talks. And of course, the really novel component of our year-long 2013 celebration of genomics will be the exhibition that we are co-developing with our good friends and colleagues at the Smithsonian National Museum of Natural History. After much anticipation and an extraordinary amount of work, the 2,900-square-foot exhibition entitled Genome Unlocking Life's Code will open at the National Museum of Natural History in June. Also planned is a significant amount of associated programming and outreach in terms of genomics literacy and education programs. And the exhibition will be resident in Washington, D.C. for just over one year, until about September of 2014, and then it will tour North America for an additional four to five years. So just for fun, shown here is a bird's eye preview of the exhibition, which will be located in hall 23 on the second floor of the museum, immediately adjacent to the Hope Diamond. The exhibition will consist of five major thematic areas that are all shown here. Each of the areas will contain engaging interactives and interesting stories that will highlight various aspects of the thematic topic. The exhibition will include stories about our health, cancer, genetic testing, personalized medicine, comparative genomics, ancestry, and the ethical, legal, and social implications of genomics. And with seven million people visiting the National Museum of Natural History each year, of which over four million visit the Hope Diamond immediately next door, we anticipate that a very large number of individuals will benefit from this incredibly creative and instructive exposure to genomics, and we look forward to every council member coming and visiting the exhibition multiple times, and perhaps seeing it in your city when it travels close to you. Well, to compliment the physical exhibition, NHGRI and the National Museum of Natural History and the Smithsonian Associates have partnered to develop a series of educational programs for the public, lectures, symposia, discussion panels, and gatherings that'll be offered from September 2013 through July of 2014. A few themes that'll be covered in this series are listed here, and as you can see, they'll be covering a range of interesting topics, and we look forward to engaging public on these and other important issues. The first of these public programs will be held on September 12th in partnership with the National Museum of Natural History and the National African American History and Culture Museum. This event will explore the role of genomics and ancestry in understanding health, culture, and history. A panel discussion will follow with members of the scientific community and the audience. Of note, NHGRI is providing funding to support an ASHG scientific roundtable on genetic inference and ancestry, which will be held September 10th and 11th, and speakers from that roundtable event will then participate in the public program on September 12th. Well, additional information on the other public programs will be forthcoming as details become available. Finally, NHGRI and the National Museum of Natural History are creating a website to promote, feature, and centralize materials related to the exhibition and other relevant public outreach efforts. The website will include a virtual tour of the exhibition, a dynamic timeline on the history of genomics, a calendar of ongoing programs and educators guide, and many other resources. It'll also offer insights into many of the exhibition's topics as well as information on basic genetics and genomics. With the URL of www.unlockinglivescode.org, the website will be updated regularly as the exhibition travels. And I should finally, I should point out that none of this, none of this, the exhibition, the website, or the associated program would not have been possible without the generous contributions of many companies, organizations, and individuals. I wanna give a special thanks to the foundation for NIH, which spearheaded those funding-raising efforts, and we're also terrific partners to work with on this project. You will see the full list of those contributors and partners when you visit the exhibition or the exhibition's website. Moving on, one of NHGRI's seven divisions, the Division of Management, is responsible for all aspects of administrative management at the Institute, and the director of that division is also known as the Institute's Executive Officer. Janice Mulaney, who had served for over five years in this position, recently left NHGRI to become the Executive Officer at the National Center for Advancing Translational Sciences, NCATS. Until a permanent Executive Officer and Director of the Division of Management is launched and completed, I've asked Allen Ralthas to serve in this role in an acting capacity. Allen has been at NHGRI for over 16 years and has served as the Institute's Deputy Director for three years. The other major personnel updates relate to important ongoing NHGRI recruitments. I recently launched the search to identify a director for the Division of Genomics and Society, one of the four divisions that constitutes the NHGRI Extramural Research Program. Recall that NHGRI Deputy Director, Mark Geyer, is currently serving as the Acting Director of this division. This position will be advertised through USA Jobs from May 22nd to June 4th. Second, we aim to expand the number of program directors responsible for the bioinformatics research activities in the Extramural Research Program. We will soon be advertising for two such program director positions. And in fact, I just got an email this morning to say that those ads will open up next week. And so important, if you know people, please point them our way. And finally, two of our divisions, the Division of Genomic Medicine of the Extramural Research Program and also the Division of Policy, Communications and Education are actively looking to recruit physicians or other senior healthcare professionals to serve various roles in their respective divisions. Well, now some information about each of these recruitments is available as document five, but as I just mentioned, one of the links won't become available until next year, next week. But meanwhile, if you have any idea of prospective candidates for any of these positions or questions about any of these important recruitments, please feel free to email me directly. Okay, moving on to general NIH updates. John Lorch has been selected to be the next director of the National Institute of General Medical Sciences, NIGMS. He comes to the NIH from Johns Hopkins University School of Medicine where he is professor in the Department of Biophysics and Biophysical Chemistry. His research group developed a fully reconstituted yeast translation initiation system and user to dissect the molecular mechanisms of each stage of the process. John will assume the NIGMS directorship in August. In the meantime, I could tell you I'm meeting with him regularly to discuss the many topics of mutual interest to our institutes. I fully expect those discussions will lead to some important and productive new interactions. And I also expect that we will have John come to make a presentation to this council probably in early 2014. Last month, President Obama announced the brain research through Advancing Innovative Neurotechnologies or otherwise known as the Brain Initiative. Brain is part of a new presidential focus aimed at revolutionary understanding of the human brain. The Brain Initiative is now associated with a hundred million dollars in the president's proposed fiscal year 2014 budget. 40 million dollars will come from the NIH to develop new tools, training and opportunities and other resources. An additional 50 million will come from DARPA for understanding the dynamic functions of the brain and demonstrating breakthrough applications. And 20 million dollars will come from NSF for supporting research that spans physical, biological, social and behavioral sciences. NIH has established a high-level working group co-chaired by Corey Bergman of Rockefeller University and William Newsom of Stanford University to define the scientific goals for NIH's investment and to develop a multi-year scientific plan for achieving these goals, including timetables, milestones and cost estimates. The past few months have brought steady progress on the big data and data science front at the NIH level. Recall that last June, a working group of the advisory committee to the NIH director, which included two members of this council, made a series of recommendations for NIH to tackle the big data problem faced by the biomedical research community. There are three major elements in those recommendations. First, a new leadership position reporting directly to the NIH director has been created called the Associate Director for Data Science. This person will be NIH's strategic and programmatic leader in data science broadly defined. On an interim basis, I am serving as the acting associate director for data science. Second, Francis Collins has convened a scientific data council, which is a high-level internal NIH group that will now oversee and coordinate NIH data science activities. This group is now meeting regularly and has significant responsibilities for overseeing trans-NIH data science initiatives and for long-term strategic planning in this area. And finally, and in a highly overlapping conceptually with the other two elements, the new Big Data to Knowledge Initiative, or BD2K, is reaching a mature stage in terms of planning. Let me now provide you more details about the first and the third of these three elements. Well, in addition to serving as the acting associate director for data science, I'm also co-chairing the search committee to identify the first permanent associate director for data science, shown here is the advertisement associated with that search. Last week was actually the initial cutoff date for applications and those received to date will be evaluated by the search committee shortly. However, the search will remain open until the position is filled. So if you know of potential candidates, please send them my way or send me their names and I will contact them directly. It's a very important search for NIH and for the broad field of computational biology, bioinformatics data science, et cetera. And so the search committee is working very hard to find the most outstanding candidates possible. The flagship component of NIH's big data efforts is BD2K, which is a trans-NIH effort designed to be transformational, catalytic, and synergistic. BD2K's overarching goal is by the end of the decade enable a quantum leap in the ability of the biomedical research enterprise to maximize the value of the growing volume and complexity of biomedical data. It's a huge task. But there's strong support for it across the NIH, including an agreed-upon plan that ramps up to over $100 million of funding per year within a few years and then goes through fiscal year 2020. NHGRI's deputy director, Mark Geyer, is leading the planning efforts for BD2K with the working group he directs having about 125 NIH staff members. And those individuals come from 24 institute centers and several other offices. Well, planning for BD2K will take place throughout this fiscal year with the launching of some of the initial elements starting in fiscal year 2014. And we expect that NHGRI will end up leading some of the elements of the program and as such will likely be bringing specific BD2K components to this council for your input. Let me just briefly remind you of the four programmatic areas of BD2K. Area one is facilitating broad use of biomedical big data. This covers policies that encourage data sharing and also ways to make shared data easier to find and use. Area two is developing and disseminating analysis methods and software for biomedical big data. This involves developing software, making software easier to find and making it easier to use, especially software for analyzing large data sets. Area three is enhancing training for biomedical big data. This covers both improvements in the existing educational framework and training for existing scientists. And area four, establishing centers of excellence for biomedical big data. These centers will address major biologically-driven big data problems. In summary, extensive planning for BD2K is well underway. In terms of a timeline, there will be a series of BD2K planning workshops beginning this summer and initiative funding will start in fiscal year 14. This program has a unique funding model with funds coming from both the NIH Common Fund and also from all institutes and centers with the Institute Center support increasing each year and then with Common Fund support going away completely by around 2020. While we're all gratified that despite tight budgets, the collective NIH leadership has identified both Common Fund monies and Institute Center monies that will allow the initiative to grow from 27 million in fiscal 2014 to 99 million by fiscal year 2016. And while those available funds for the next three fiscal years shown in green on this slide are less than those originally requested due to the obvious overall budget constraints, these amounts are still sufficient for initiating a strong program and we're very grateful that we're able to launch this on schedule. Turning then to the broader set of budgetary issues and constraints. When we last met in February, the federal government was at that time being funded by a continuing resolution through the end of March. Congress has now passed a year long continuing resolution that would keep the NIH operating for the rest of fiscal year 2013 at fiscal year 2012 levels. However, the other significant development was the much talked about sequester that was implemented because Congress failed to act before the March deadline. Therefore, as required by the Budget Control Act of 2011, our budget was reduced by 5.1% due to the sequester. Because of all the complexities of the sequester combined with the continuing resolution, there was then an additional 0.7% cut to the NIH budget. So the overall reduction is actually 5.8% relative to fiscal year 2012. So at the end of the day, NHRI's final fiscal year 2013 budget is lowered by about 5.8% compared to last year for a total of $483 million. This is obviously an incredibly challenging time for us as we now move forward in implementing such a 5.8% reduction. With respect to our extramural research program, last week we posted our 2013 funding policy on our website. One important element of that policy is a 4.5% reduction to non-competing awards consistent with the NIH-wide policy. And meanwhile, competing awards are being examined on a case-by-case basis. Well, needless to say, we find ourselves in one of the most unusual and unfortunate budgetary circumstances in a long, long time. Things are particularly bad this year, but this comes at the end of a multi-year trend of decreasing budgets. For example, relative to our specific budgets and other economic metrics, the purchasing power with our research dollars has dropped something like 20% over the last decade. Well, rather than standing by and watching the political gladiators battle for higher NIH budgets, some of us at NHGRI continue to explore creative options for funding our important genomics research. Some ideas that have bubbled up from the rank and file include raising funds by NHGRI car washes, or possibly NHGRI bake sales. I mean, Mark Geyer makes a really mean homentation. I'm sure we can make a lot of money off that. But I would say that I, however, think that desperate times call for desperate moves by desperate institute directors. I am one of those. I think to raise money to fund our genomics research, we need to move beyond high school-type fundraising activities like car washes and bake sales and use the power of the web and YouTube. So along those lines, I note that my directors reported every council meeting is videotaped and featured on Genome TV channel of YouTube, and many, many, many people watch these videos. I also note that my laptop gets prominent viewing during those videos, giving great exposure to the viable label Antisoni. Now, why should Sony benefit from that exposure? Why not have NHGRI benefit by selling advertisement space on my laptop? So my solution is as follows. To do this, okay? Rent advertisement space on my laptop looks great and have people phone in to be able to get that space for the next director's report. Don't you think that'll solve it? Okay, all right. Had to inject a little bit of humor to otherwise gloomy budgetary forecast. So I will move on now. So fiscal year 2014. Well, now the fiscal year 2013 budget has been finalized to focus moves to fiscal year 2014. Accordingly, on April 10th, President Obama sent his proposed fiscal year 2014 budget to Congress for their consideration. It includes $31.3 billion budget for NIH and $517 million budget for NHGRI. Well, Congress is now starting to examine the proposed budget through appropriations committee hearings. Last month, Secretary Sebelius testified before the House and the Senate appropriation subcommittees charged with drafting the budget for the Department of Health and Human Services. And last week, Francis Collins and a subset of Institute directors testified before the same Senate subcommittee. To be really candid, at this point, it is too early to predict whether the appropriations bills emerging from the House and Senate will match the President's request. I'll keep you posted. I think it is very difficult to know right now where we are heading with this fiscal year's appropriations. One positive development to report that relates to the U.S. Congress occurred two weeks ago when a bipartisan delegation from the U.S. House of Representatives visited the NIH. House Majority Leader Eric Cantor led the delegation and he was joined by eight other members from both sides of the aisle, including two physicians, one veterinarian, a nurse and a clinical psychologist. I was able to join Francis Collins and a few other Institute and Senate directors in meeting with the delegation. For many of the members, it was their first visit to the NIH campus. So Francis gave an overview of NIH before opening up the discussion. The members raised a number of important issues, including the effects of sequestration on research funding and the appropriate level of indirect costs, as one set of questions. The meeting was actually very cordial. The delegation unanimously expressed great support for NIH. I'd point out that the House members speaking in the photo on the bottom right is Congressman Andy Harris of Maryland, who's the only member of the Congress who has ever had an NIH grant. Dr. Harris is an anesthesiologist who was previously a physician scientist at Johns Hopkins University and is very interested in what's going on at NIH and we had a very good set of discussions with him and many meetings have and will continue to take place with Dr. Harris. During the visit, members also visited Dr. Lou Stout's Cancer Genomics Laboratory, where they also heard about work going on as part of the TCGA program. One particular proposal within the President's fiscal year 2014 budget that has garnered a fair amount of attention is a plan to significantly restructure federal science, technology, engineering, and mathematics, commonly known as STEM, education programs. Over the past 10 years, a series of reports have expressed concern over the large number of federal STEM programs and recommended better coordination among agencies. The President's fiscal year 2014 budget responds to those reports by proposing a reorganization of federal STEM education program funding to promote strategic coordination and investment in education activities. Those activities are proposed to be focused through just three agencies going forward, the Department of Education, the National Science Foundation, and the Smithsonian Institution. As part of this realignment, nine federal agencies are scheduled to terminate 78 programs, including nine at NIH. The President's proposal will provide an additional $100 million to the Department of Education to improve K-12 instruction, another $25 million to the Smithsonian Institution to develop infrastructure to support K-12 instruction and engagement, and $51 million to the National Science Foundation to support STEM undergraduate education and development of a national strategy for fellowships. There will certainly be an extensive amount of discussion and debate about this proposal in the weeks and months to come, and we are certainly gonna follow that discussion. So let me move now on to some general genomics updates. Francis Frank Ruddle passed away in March. He was one of the first scientists to produce a transgenic mammal, a mouse. He was also one of the first researchers to map genes to specific chromosomes, laying some important groundwork for the Human Genome Project. François Jacob, a research partner of Jacques Manot, passed away in April. He shared the Nobel Prize in Physiology and Medicine for discovering that cells can switch on and off certain genetic information through regulatory genes. The new Breakthrough Prize in Life Sciences has been awarded to 11 scientists. This new prize is sponsored by Genotex Art Levinson, Google Sergey Brin, 23andMe's Anne Wojcicki, Facebook's Mark Zuckerberg and Priscilla Chen, and Yuri Milner, the founder of mail.ru group. The first set of winners include some very familiar names to NHGRI, including David Botstein, Tisha DeLang, Eric Lander, Charles Sawyer, and Bert Mogelstein. Congratulations to all of them. And recently, a number of individuals with ties to NHGRI were elected to the National Academy of Sciences. That list includes Jeff Bucca, Marcus Feldman, Nehal George, Mary Lindstrom, Norbert Paramount, Steven Quake, Lou Stout, who I mentioned earlier, Hunt Willard, and Fred Winston. And the same holds true for some recently elected fellows of the American Academy of Arts and Sciences, AAAS, that list includes David Allschuler, Marty Blazer, Eugene Coonan, John Liss, Jim Lufsky, and Jonathan Pritchard. And finally, a number of individuals with ties to NHGRI were recently selected as new investigators in the Howard Hughes Medical Institute. That list includes Joanne He, Vamsi Mutha, Aviv Ragev, and David Reich. Moving on, the lawsuit over myriad genetics BRCA1 gene patents, and possibly gene patents all together, is heading towards a final resolution. The case began in 2009, when several pathology societies, clinical pathologists, and breast cancer patients challenged the US Patent and Trademark Office, Myriad Genetics Incorporated, and the directors of the University of Utah Research Foundation, over Myriad's BRCA1 and BRCA2 related patents. After working its way through the lower courts, the US Supreme Court heard arguments in the case on April 15. I was actually fortunate enough to attend those arguments as a guest of the US Solicitor General, whom I had helped to brief in preparation for his argument, shown here is the line of individuals that morning. I took this picture, waiting in front of the Supreme Court, some of which had lined up the night before to be able to get in to hear the arguments. And then here is a photo of me, along with Francis Collins, Eric Lander, Bob Cook-Degan, and some of Bob's students at Duke, some of them were the ones camping out for the Supreme Court. On the steps of the Supreme Court after the hearing, I would sum up. My reaction to being there for this important event in five words, it was interesting, it was amazing, it was historic, but it was also surreal, and it was incredibly frustrating, especially with respect to how quickly it all happened, like about an hour and 10 minutes, and that was it. That made it frustrating, I thought. The court is expected to issue their ruling by the end of June. It's difficult to speculate on how they will rule, but most analysts are suggesting the court will agree with the US government position, finding that isolated but otherwise unmodified human genes should not be patent eligible, but allowing CD&A patent claims to remain. I've asked council member, R.D. Rye, who's not here today, but was that there at the Supreme Court in person? I've asked her to discuss the court's decision since they'll come out this summer at our September council meeting, so we'll have a discussion about that at September council meeting. As more of the Affordable Care Act is being implemented, we are keeping an eye on what it means for the implementation of genomic medicine. Recently, a joint FAQ was issued by the Department of Labor, the Department of Health and Human Services, and the Department of the Treasury, claiming or clarifying that BRCA testing is covered by the Affordable Care Act. Under the Act, certain healthcare plans are required to cover for no charge preventative services that are recommended by the US Preventative Services Task Force. However, there was a question as to whether that task force recommendations for BRCA testing covered the testing itself or only the Genetic Counseling Services. The agencies have now clarified that the recommendation covers both BRCA testing and Genetic Counseling, if appropriate for a woman as determined by her healthcare provider. Associated with this, the US Preventative Services Task Force is now working to update its BRCA testing recommendations and recently issued an updated draft for public comment. Late in February, the American College of Medical Genetics and Genomics, ACMG, and the American Academy of Pediatrics, AAP, released a joint policy statement on the issues related to genetic testing and screening in children. This statement represents an update of the previous policy recommendations by ACMG and AAP from 1995 and 2001 respectively. This new statement emphasizes that decisions about testing and screening should be made with the interest of the child paramount. It expresses strong support for newborn screening but opposes routine carrier testing that would not provide health benefits in childhood and similarly recommends deferring predictive genetic testing for adult onset conditions. The recommendations were published in the Journal of Pediatrics with a more detailed discussion and a complimentary paper in the Journal of Genetics and Medicine. A few weeks after issuing the joint statement with the AAP, the American College of Medical Genetics and Genomics, ACMG, published recommendations for reporting incidental findings that arise from clinical exome and genome sequencing, building on their 2012 points to consider in the clinical application of genomic sequencing. Among the authors of the recommendations are a pair of council members, Amy McGuire, Bob Nussbaum, Les Beesecker, Chief of the Genetic Disease Research Branch and NHGRI's Intramural Research Program was co-chair of the working group that developed these recommendations. And you'll be hearing more about these recommendations from council member Bob Nussbaum later in the open session. In other professional society news, the American Medical Association, AMA, published a white paper on personalized medicine in February. The paper recognizes how genomics will influence the practice of medicine and highlights the need for important policy questions to be addressed in order for genomic medicine to be realized. Paper also expresses the position of the AMA on a range of policy issues, including the call to strengthen privacy and protections against genetic discrimination. It also affirms AMA's strong support for the NIH genetic testing registry. A new journal titled Molecular Genetics and Genomic Medicine was launched last fall, with the first issue released last month. Max Munka, Chief of the Medical Genetics Branch and NHGRI's Intramural Research Program is the new journal's founding editor. Molecular Genetics and Genomic Medicine is one of Wiley's open access journals and will publish research in all areas of human, medical, and molecular genetics and genomics. NHGRI continues to feature Genome Advance the month on our website, genome.gov, publications that were featured since the last council meeting described encoding information in DNA, DNA editing in human cells, using the Cas9 nuclease and engineering zinc fingers to target cells. Turning to my regular genomics in the news section, in case you missed it, I want to point out the value of genomics as receiving recognition at the highest levels. In his 2013 State of the Union address, President Obama directly referred to the economic impact of the Human Genome Project in support of continued federal biomedical research investments, citing the 2011 Battelle report that provided evidence for a 140 to one return on investment from the Human Genome Project. As an aside, I understand that Battelle will be updating their economic impact report this year with figures for 2012 and 2013. The anticipated release for that new report is in June. Also in the news, the application of genomic technologies for prenatal DNA sequencing was named as one of the top 10 breakthrough technologies of 2013 by MIT Technology Review. And as always, there have been a number of genomes, sequence that have garnered recent press attention. These include reports about the platyfish, the ah lemur, the sea lamprey, sila canth, zebrafish, the Chinese softshell turtle, and the green sea turtle. There continues to be some mutterings about the sequencing of the Sasquash genome, although none of this has yet to be substantiated. I just mentioned it for those interested. Okay, moving on then to NHGRI's extramural research program and starting with the flagship component of our genome sequencing program, that being the large-scale genome sequencing analysis centers who are involved in undertaking a number of projects mostly related to complex disease and cancer. In the most recent quarter, the three centers produced over 100 terabases of sequence. The equivalent of 1,000 high coverage whole human genome sequences are about 13,500 whole exome sequences. This pace puts them on track to increase production by 25% compared to last year. At the centers, there are over 200 ongoing projects focused on cancer, complex disease, rare diseases, and comparative sequencing. Meanwhile, these groups together have over 25 papers either publisher and press in the past quarter alone. Among the major efforts being pursued by our large centers is the 1,000 Genomes Project. Sequencing is now complete for the 1,000 Genomes Project, with data now having been generated for 26 different populations. These data reflect the following. For 2,683 samples, there'll be low coverage, 3X or higher, whole genome sequence. For 2,658 samples, there will be whole exome sequence. For 2,642 samples, there'll be both whole exome and low coverage whole genome sequence. And for 465 samples, there will be deep whole genome sequence generated by complete genomics, including about 150 children in trios with parents sequence by other parts of the project. 1,000 Genomes Analysis Meeting was held two weeks ago at the Cold Spring Harbor Laboratory Genome Biology Meeting during which plans were finalized for analyzing this last data set. And the next 1,000 Genomes Analysis Meeting will take place prior to the American Society of Human Genetics annual meeting in October. The Cancer Genome Atlas program continues to generate prodigious amounts of data and publish groundbreaking papers. TCGA investigators met in Seattle earlier this month to discuss the analysis of the over 8,000 samples from 26 types of cancer, with all the data being made available on the TCGA portal. The TCGA network has had three major papers that were recently published or now in press. On May 1, a description of the genomic and epigenomic landscape of acute myeloid leukemia work led by Tim Lay and council member Rick Wilson at Washington University was published in the New England Journal of Medicine. On the same day, the TCGA paper on endometrial carcinoma work led by Doug Levine of Memorial Sloan Kettering Cancer Center and Elaine Martis at Washington University was published in Nature. And the TCGA paper on renal clear cell carcinoma work led by Richard Gibbs and Chad Crichton at Baylor College of Medicine has been accepted for publication and will be out next month. For interest, one particular thing to illustrate the Circos plot shown here illustrates the discovery power of TCGA. Shown are all of the gene fusions observed in the 200 tumor samples analyzed for the acute myeloid leukemia project. In frame, gene fusions are shown in green and out of frame fusions in orange. Although gene fusions have been studied in AML for many years, of the 128 fusions revealed by the TCGA study, 71, that's more than half, had not been reported previously. Another component of NHGRI's genome sequencing program, the Centers for Mendelian Genomics at the University of Washington, Yale and the combined center at Baylor Hopkins aimed to elucidate the molecular basis for as many Mendelian disorders as possible by genome sequencing. With respect to disease gene discovery, to date, more than 9,000 whole exome sequences have entered production pipelines for studying 526 Mendelian disorders involving all major organ systems. And to date, 64 disease genes and 116 candidate disease genes have been identified providing insights into new pathways, mechanisms and models of inheritance. In terms of collaborations and outreach, these three centers collaborate with researchers worldwide to solicit samples and disseminate methods. So far, they've worked with 323 investigators from 189 institutions in 30 countries and they've given over 100 presentations about the program. The centers had their first face-to-face meeting in March. A new working group was formed to focus on data analysis. They also discussed potential new collaborations, especially with the three large-scale genome sequencing and analysis centers. Relevant to our Centers for Mendelian Genomics program, the International Rare Diseases Research Consortium was launched in April of 2011. This consortium aims, by the year 2020, to develop a diagnostic test for most rare disorders and new treatments for 200 rare disorders. The consortium is governed by an executive committee, three scientific committees and a number of working groups. NHGRI is represented on the executive committee, Jane Peterson previously, but now Jeff Schloss has taken over to represent us on that committee. Mike Bombshed of the Coordinating Center for the Center for Mendelian Genomics is co-chair of the diagnostic committee, which focuses on solving rare diseases and genome-wide diagnostic sequencing. The first scientific meeting of the consortium took place in Dublin in April, at which Mike Bombshed made a presentation about the Centers for Mendelian Genomics program. And then the consortium organized a panel discussion at the 2013 Bio-International Convention in Chicago and NHGRI program director Lou Wang participated in that panel and discussed the Centers for Mendelian Genomics program. Another component of NHGRI's genome sequencing program, the Genome Sequencing Informatics Tools, or GSIT program, has adopted the name ICIC Tools as part of its public outreach effort. This program, comprised of six projects, is developing methods to provide access to sequence analysis tools for the community of users outside of large centers. The ICIC Tools projects are hosting workshops to help users learn how to apply improved tools for sequence analysis. The next workshop will be July 9th and 10th at the Broad Institute, where users will work with the popular genome analysis toolkit, GATK package. As further outreach, the GATK group supports a forum where registered users can join live Q&A sessions that are designed for questions that are too complex for online support. Last month, 150 scientists participated in the annual grantee meeting for NHGRI's $1,000 genome technology development program in which grantees shared their results and were then joined in the last day by non-grantees working in the field. The most striking results reported include demonstrations by several groups for methods for direct reading of modified cytosines and genomic DNA, fabrication of solid-state nanopore rays, and as a spin-out of experiments to sequence DNA using nanopores, early demonstrations of protein analysis using nanopores. A new set of grant applications for this program will be discussed in the closed session of this council meeting. Moving on to ENCODE, the goal of Encyclopedia of DNA Elements or ENCODE Project is to create a catalog of all functional elements in the genome and make that catalog freely available as a resource to the biomedical research community. A widely attended, actually I was there, a standing room-only tutorial on using ENCODE data to understand the role of genetic variation in human disease was held at the Cold Spring Harbor Laboratory Biology of Genomes meeting two weeks ago. In ENCODE, consortium meeting will take place later this month at which the data production centers, data analysis and coordination centers, computational analysis groups, and technology development groups will all present updates on their projects, begin to develop coordinated analysis plans, and finalize consortium goals and policies. Meanwhile, cross-species, integrative analyses of functional elements is well underway with manuscripts submitted or in final preparations, and both mod ENCODE and mouse ENCODE are also writing sets of companion papers to go with the major papers. Mike Payson, one of ENCODE's program directors gave a talk about ENCODE at TEDMED 2013, held at the Kennedy Center in Washington, D.C. in April. The talk was entitled, Can an Orchestra of Scientists Find the Hidden Music in Your DNA? And it shed light on how collaborators can help unlock more DNA secrets with experiences in the ENCODE project used as examples. NHRI would also like to congratulate Rebecca Loden and Julie Wexler, two former ENCODE program analysts who are each awarded an NSF graduate research fellowship. Rebecca's currently a graduate student at Washington University and Judy is a graduate student at UC Davis. Following Council's agreement in February to renew the Centers of Excellence in Genomic Science SEGS program, NHGRI and NIMH published a new program announcement in April with modifications that broaden the scope of the SEGS program so it became better aligned with NHGRI's new strategic plan. Letters of intent for SEGS and their associated diversity action plans are due in June and applications are then due in July. The current program announcement is for one year. Later this year we will issue a new program announcement for three more SEGS application receipt dates. This is because NIH is making a transition to electronic submission of these more complex grant applications. This year's annual SEGS grantee and diversity action plan DAP meeting will be hosted by the SEGS at the Medical College of Wisconsin and the University of Wisconsin will be held in Madison, Wisconsin in October and shown here as a group photograph from a previous such meeting. During the first quarter of 2013, the Phoenix toolkit an online resource of standard phenotypic and environmental exposure measures met an exciting milestone, the 1,000th registered user. At the end of April, there are now close to 1,100 registered users. In addition, seven new funding opportunity announcements, FOAs, that strongly recommend the use of Phoenix measures were published in 2013 for a total of 35 such FOAs from a variety of NIH institutes and centers. And lastly, the NIH recently launched a web portal to improve access to information about NIH supported common data element initiatives such as Phoenix and to assist investigators with tools and resources for developing protocols for data collection. NHGRI program staff participates in this trans-NIH effort in which Phoenix measures have had a very strong presence. You may recall the Genetic Association Information Network or GAIN was established to investigate the genetic basis of common diseases by creating a network of six collaborative genome-wide association studies, include those studying ADHD, depression, type 1 diabetes, and other conditions. Since making GAIN study available through DBGAP in 2007, the GAIN Data Access Committee has received and reviewed over 1,000 project requests. In April, a commentary describing the experience of the GAIN Data Access Committee was published in the American Journal of Human Genetics. Over five years of experience with this controlled data access model has demonstrated substantial use of GAIN Data by investigators from academic, nonprofit, and for-profit institutions with relatively few policy violations. As you can see from this table, which was included in the commentary, roughly 200 project requests have been submitted to the GAIN Data Access Committee in each of the past several years with the majority being approved. The availability of GAIN Data has allowed for advances of both understanding of genetic underpinnings of specific diseases and the development and refinement of statistical methods for identifying genetic and environmental factors related to complex common diseases. The NHGRI GWAS catalog identifies, curates, and disseminates data from the published GWAS literature in a user-friendly downloadable resource. Recently, the iconic GWAS ideogram was updated to include studies from 2012. In addition to the snapshot at our genome.gov site, an interactive and enhanced version of this graphic can be found on the EBI website shown here. Zooming in on a region of chromosome 16, for example, and clicking on this orange dot at 16Q12, for example, shows information about the association of the FTO locus with type II diabetes. Also at this website, there are now graphics customized for the most common and popular searches of the catalog. For example, if you want to search catalog for obesity, such as that shown here, and these have been generated and are conveniently available for download. The population architecture using genomics and epidemiology page program focuses on elucidating the genetic variants, underline a wide range of common diseases and traits in large ethnically diverse cohorts. Recently, page-completed metabachip genotyping of over 60,000 non-European participants making this one of the largest, if not the largest collections of well-phenotype diverse ancestry participants. And analyses on over 20 diseases or traits are now underway. And in recent months, page has published several papers on obesity and diabetes and lipids, as shown by this flurry of screenshots from some of these papers. The phenotype integrator, or FIgini, is an NCBI NHRI collaboration to integrate GWAS data from the NHRI GWAS catalog and DBGAP with other genomic resources at NCBI. This resource has been introduced to council previously, but here we provide a few updates of interest. The search-specific ideogram is now available in a high resolution and downloadable format to facilitate use in posters, papers, and talks. A FIgini overview paper by Ramos et al is now in press at the European Journal of Human Genetics. And finally, FIgini was honored as a silver medallion poster at the recent AMIA summit on translational bioinformatics. The first set of genomic medicine pilot demonstration projects were awarded on May 1st. You can see the four award recipients here. The goals of the program are to develop best practices for incorporating genomic information into healthcare settings with a program including new and ongoing genomic medicine projects. The core source show will hold its first steering committee meeting in July. And the reissued RFA for the program has been released with applications due in July as well. You may recall that NHGRI's genomic medicine working group held its fourth genomic medicine meeting this past January and representatives from 10 different professional societies across a range of disciplines as well as representatives from two regulatory bodies attended the meeting. One of the outcomes of the meeting was the creation of an Inner Society Coordinating Committee for Practitioner Education and Genomics, or ISCCPEG. The goal of this new group is to facilitate professional societies efforts in educating physicians and other practitioners in the use of genomic medicine in clinical care. The committee has anticipated to include one representative from each interested professional society and NIH Institute and Center. We currently have representation from 13 medical professional societies and 11 NIH Institutes and Centers. And the committee expects to hold its first in-person meeting next month. Turning then to our Ethical Legal and Social Implications LC Research Program, the Returner Results Consortium and the Clinical Sequencing Exploratory Research, CSER program will hold their second joint meeting on May 22nd and 23rd, that's later this week. The meeting will bring together investigators from CSER, as well as the R01, R21, and other independent projects funded by the LC Research Program related to Returner Results. The meeting will include a wide range of topics of interest to both CSER and the Returner Results Consortium members, including the recent ACMG recommendations on return of incidental findings, legal issues related to liability, as well as the Clinical Laboratory Improvement Act, CLIA, and implications of recent findings and identifiability of genomic data for data sharing. In the fall of last year, NHGRI established the Genomics and Society Working Group as a working group of this council. The mission of the Genomics and Society Working Group is to provide advice to council and to NHGRI on short and long-range planning and priority study for genomics and society activities in the Institute, broadly defined, with particular emphasis on the LC Research Program. The first meeting of this working group was held in April, and they are planning for their next meeting coming up in the fall. But Pamela Sankar is gonna give you more details on a report about the first meeting of this working group later in the open session. Similarly, earlier this year, NHGRI invited 20 experts in genomics, genomic medicine, and training to a workshop that discussed the future of NHGRI's training and career development programs. This was actually the first review of NHGRI's training program since the Human Genome Project began, and yet the needs in training and career development have changed substantially over the last two decades. But with the publication of NHGRI's new strategic plan in 2011, there is a need to assess and realign the Institute's training and career development programs. The expected outcome of this workshop and subsequent discussions will likely be new FOAs for NHGRI training programs, but I'm gonna leave that discussion to Betty Graham, who later in the open session is gonna be given a presentation about our recent workshop and some of our thinking around the recommendations. So, that's what I wanted to say about our extramural research program. Let me now move to the NIH Common Fund, where as always, NHGRI is heavily involved. Let's start with one of the oldest of the Common Fund programs that we were involved with, the Molecular Libraries Program. Molecular Libraries Program offers researchers access to the screening capacity needed to identify small molecules that can be optimized as chemical probes to study the functions of genes, cells, and biochemical pathways in health and disease. Chemical probes may also be used to validate new targets. The program began as a pilot in 2004 to develop screening centers, and then the production phase then began in 2008. But support for the Common Fund is gonna end in May of 2014, so we really are now in the final year of the production phase of this program. Several achievements have been made over the past five years of the production phase. These include the initiation of 352 probe discovery projects and the completion of 340 high throughput screens and the production of 348 small molecule probes. The Molecular Libraries Program's screening date is available in PubChem for every project, and probes are published in the NCBI bookshelf. The next Common Fund project to mention is the Knockout Mouse Phenotyping Project, COM2. The goal of COM2, which was launched in the fall of 2011, is to make and phenotype 2,500 knockout mouse strains over five years. The phenotype data will be deposited into central core database, and the mouse strains will be available from the COM repository. The project is part of the International Mouse Phenotyping Consortium, IMPC, whose overall goal is to make over 5,000 strains during these five years. These graphs show a typical report coming out of COM2. The top graph shows ESL micro-injections, while the bottom graph shows the production of mouse strains for which the ESL has transmitted through to the germline. The yellow line reflects the project's goals. The blue line shows the actual production. The COM2 annual meeting was held a few weeks ago, at which overall progress at the international level was reviewed by the IMPC Panel of Scientific Consultants. And finally, the Bloomsbury report on mouse embryo phenotyping was published in March. This presented the rationale for the embryonic lethal phenotyping supplement that was recently granted for roughly $9.6 million by the NIH Common Fund. The Genotype Tissue Expression, G-TEX project of the Common Fund aims to study human gene expression and regulation of multiple tissues through genomic analyses of rapid autopsy samples. The goal is to gain insights into the mechanisms of gene regulation and in the future its disease-related perturbations. G-TEX released its pilot data in April through DBGAP. This includes genotype data from 182 postmortem donors and over 1,800 RNA-seq studies from 38 different tissues. Shown in the figure are data for nine organs with 90 or more samples analyzed. On June 18th, G-TEX will hold the first G-TEX community meeting in Boston. And finally, there was a robust response to an RFA, a design to enhance G-TEX with additional molecular assays. And after review in June, these applications will come to this council meeting in September. Moving on, the Library of Integrated Network-Based Cellular Signatures or LINX project aims to create a network-based understanding of biology by cataloging changes in gene expression and other cellular processes that occur when cells are exposed to a variety of perturbing agents and by using computational tools to integrate this diverse information into a comprehensive view of normal and disease states that can be applied for the development of new biomarkers and therapeutics. In March, a LINX data forum was held at Harvard Medical School. Approximately 150 people attended this forum and over 90 of which were non-LINX scientists, including 15 representatives and researchers from pharma. In addition, 40 people from Europe and Asia attended via a live video cast. The forum showcased the LINX tools that were released in November and provided interactive hands-on demonstration sessions that allow participants to try out the new tools with expert guidance. The follow-up LINX VIZ-BI or VIS-B meeting afforded an opportunity for LINX groups to introduce the broader biomedical visualization community to the data visualization and analysis challenges being faced by LINX. Finally, the NIH Common Fund has approved a phase two for LINX, which will begin in fiscal year 2014. The Protein Capture Reagents program is in its third year. The three production centers, one antigen center and two antibody centers are focused on production of human transcription factor affinity reagents. All seven of these groups were recently subjected to site visits by NIH program staff and external advisors. There's been an overall slowdown in production due to a bottleneck in antigen supply and the unforeseen difficulty in providing two different antigen formats to two different antibody production groups. The program staff and the external advisors are working with the centers to solve this bottleneck and to get production back on track. The biennial EU Aphonomics meeting was held in March. This program is a European Commission funded effort with similar goals as the Protein Capture Reagents program. The two programs are looking to expand their collaborative efforts and the Protein Capture Reagents program is also in the process of strengthening ties with the European Human Protein Atlas program. Finally, the first affinity reagents emanating from this program have been deposited in public repositories. Moving on to H3Africa, the Human Heredity and Health in Africa program which provides funding directly to African institutions to support genomics research, had its second consortium meeting in Ghana last week. I was supposed to attend, but due to mechanical problems on a United airplane, I never got there. But nonetheless, the first day was devoted to a series of working group meetings so that these groups could finalize policy recommendations that were then presented to the H3Africa Steering Committee for revision and enactment. Immediately following the H3Africa meeting, there was a joint meeting with the African Society of Human Genetics which began on May 19th and then ends today, that the H3Africa meeting was held back-to-back with the African Society of Human Genetics meeting was no coincidence and as part of H3Africa's outreach effort to engage African scientists across the continent. The next H3Africa consortium meeting will be held in Johannesburg, South Africa in October and will coincide with the South African Society for Human Genetics Congress. And the last of the Common Fund programs to talk about the Undiagnosed Diseases Network, UDN is being established across the country to increase the capacity for and the use of genome sequencing and the diagnosis of rare and new diseases. The network also hopes to aid in the management strategies for patients with such disorders. The Undiagnosed Diseases Network has two funding opportunities with applications for both due in June. First, the Undiagnosed Diseases Gene Function Research R21 solicitation will support gene function studies to investigate the underlying genetics, biochemistry, and or pathophysiology of newly diagnosed diseases in association with gene variants identified through the Undiagnosed Diseases Network. And clinical sites for Undiagnosed Diseases Network U01 solicitation aims to add to and build upon the NIH Intramural Research Program's Undiagnosed Diseases Program. This program seeks to provide improved patient access to state-of-the-art diagnostic methods which will be pursued by expanding the available expertise in facilities serving patients with these unusual disorders and by accelerating discovery and innovation and diagnosing and treating these patients. So moving on to our division of policy, communications, and education, just several updates. In late 2009, NHGRI began distributing its video content on Genome TV, a channel on YouTube.com. Since then, NHGRI has produced and posted more than 630 videos ranging from recorded webcasts of this council meeting to major events, such as our recent symposium celebrating the 10th anniversary of the completion of the Human Genome Project. As of April 29th, Genome TV had 5,159 subscribers, 5,159 subscribers, and the videos on Genome TV had been viewed more than 1.1 million times. While you can access all the videos on Genome TV directly through YouTube, we've also conveniently and very recently organized all the institutes, Genome TV, video assets on our website, specifically at genome.gov backslash Genome TV. In the upper right corner of the page, users can also see any live webcasts currently underway. In addition, the broadcast media tab on the lower left of the page links to full resolution, high definition video that news organizations and other broadcasters can download directly and use in their shows. And for historic purposes, the archive video tab in the lower right links to older videos that were produced prior to the middle of 2007. But by creating this page, we're hoping people have one place to land and conveniently see in very organized way all the different video assets that we have organized around specific areas. I will tell you that I am a big enthusiast of our Genome TV channel. When I travel, especially abroad, people say very nice things about it. And I think our general video-based outreach efforts are important for the institute to do. And one of the reasons for this is that, not infrequently, I get a feel-good email that just makes me smile all over when I otherwise crazy and stress-filled day. So I just wanted to share one with you that came. So as anecdotal evidence of Genome TV's outreach, here's an email I received back in March from someone at Lahore College for Women University in Pakistan. This individual asked specific questions about my personal favorite Genome TV video, the one that Carla Easter and I produced demonstrating how to purify strawberry DNA using materials you can find in your kitchen. But the thought of someone in Pakistan watching, being able to watch Carla and I do a laboratory demonstration, figure out how she might use it, or he or she might use it, and then send me an email with a technical question. It just made me smile. It just made me just, and again, when I travel abroad similarly, I have people come up to me constantly compliment the institute for all the video resources we make available. Okay, Genomics and Medicine lecture series began its third round of lectures earlier this month. The lecture series is a collaboration between NHGRI, Suburban Hospital in Bethesda, and the Johns Hopkins University School of Medicine to educate healthcare professionals about the increasing role of genomics in clinical care. This round of lectures will focus on genomics and oncology, and will include a special lecture on integration of genomics into nursing practice. Lectures in this series have been held monthly since December 2011 as part of Suburban Hospital's grand rounds. Now, the lectures themselves are attended by about 80 to 100 in-person practicing physicians, but all the talks are videotaped, and guess what, are made available on the Genome TV channel of YouTube, and are being watched widely. And finally, for this division, to celebrate DNA Day 2013 and in partnership with the National Museum of Natural History, NHGRI held a program for over 250 high school students from eight different local schools in April 19th at the National Museum of Natural History. While at the museum, these students listened and participate in a question and answer session with a panel of genomics researchers, and were sent on a scavenger hunt throughout the museum, which illustrated how genomics is relevant to many of the current exhibitions at the museum. And students also participated in hands-on genomics activities and concluded their busy day, by viewing an IMAX film. And then meanwhile, staff from NHGRI also celebrated DNA Day 2013 in partnership with Megara Evers College, the Brooklyn Public Libraries, and five Brooklyn High Schools. As part of the day, students spent two hours isolating DNA from cheek cells, and discuss the relevance of ethical issues in genomics research. And finally, and in winding down, let me just give you a few highlights from NHGRI's intramural research program, starting out with an award, Elaine Ostrander, chief of the Cancer Genetics Branch and NHGRI's Intramural Research Program, received the International Canine Health Lifetime Achievement Award for her leading role in sequencing and analyzing the canine genome, and thus providing the lasting legacy for improvement of dog health and the understanding of several human diseases. In terms of another anniversary, NHGRI founded the Social Behavioral Research Branch almost 10 years ago, on December 4th, 2003, making it the seventh of NHGRI's branches in its intramural research program. The branch is planning various elements or events to celebrate their 10th anniversary. For example, Dr. Lerman's and Shield's paired lecture that they gave as part of our commemorative activities also served to kick off the celebration of the 10th anniversary of the Social Behavioral Research Branch. Although then, in October, a larger celebration is being planned, an event that will include two internationally recognized speakers, NIH colleagues, alumni, trainees, and visiting faculty. It will also be an afternoon exhibition that will include posters and interactive exhibits to showcase innovative science of both intramural and extramural genomics and society programs. And finally, some recent highlights from NHGRI's Intramural Research Program include the following, a study by an international research team that included Ellen Sidranski and Tara Wolfsburg reported that people who carry gene alterations that cause Gauchay disease have an elevated risk for Parkinson's disease and even higher probability for dementia with Lewy bodies. A large study by a consortium that includes Charles Rotimi and members of the Center for Research on Genomics and Global Health identified genomic regions associated with body mass index among people with African ancestry. A team of researchers led by Elaine Ostrander studied dogs with squamous cell carcinoma in the digit and established the genetic cause of the disease. Standard poodles are among those at highest risk and the condition only affects standard poodles with dark coats. And Jim Mulligan and colleagues at the Anantian Tramural Sequencing Center collaborated on a study with researchers at Duke University that could help researchers determine which proteins to use investigational vaccines to induce antibodies capable of preventing infection from a ray of HIV strains. And with that, I will close with some thanks. Personal thanks to all the NHGRI staff. I asked them at least 50 to 60 of you who helped pull these many slides together that I just covered. I couldn't do this alone. It's totally a group effort and thank you for helping. And as always, a special thanks to Chris Wetterstrand who's the ringleader of these slides and coordinating the material and getting them to me to produce the final PowerPoint. This is actually a screen capture from a video trailer about the Smithsonian Genomics Exhibition that includes an interview with Chris who was among the many at NHGRI that has contributed greatly to the exhibition's development. All sorts of videos being produced and will be featured in various ways in the next few months. And also a big thanks to Larry Thompson, Judy White and the NHGRI web team for making my director's report into the electronic resource on the web. And with that, I will stop and happy to take any questions. Bob. Eric, so I really enjoyed your alternative fundraising approaches. Oh, it fell. I wanted to ask you whether there's been some thought of approaching the PCORI and seeing whether some of the genomics and medicine initiatives that you're interested in doing could be done in collaboration with them. Absolutely. Those, I've joined at least one such meeting. There are many meetings going on that involve the NIH director along those lines. There is tremendous, there is tremendous potential overlap as you rightly point out, not only with what we're doing, but with broadly what one could imagine being done and today with some of the scientific opportunities we have today. Absolutely. But I would also say that's being driven at the NIH level, not at individual institute levels. I think Francis is on the board of governors at PCORI. I think that sounds right. Yeah. That sounds right. Yeah, I've been monitoring your live, yeah, right there you got it, that the live feed and that does show up very well, but I also noticed when Bob Nussbaum was talking and the camera goes over there, so basically all of these are potential. We can have little laptop covers. So just, yeah. That's a great idea. Although I'm looking around a console table and there is a heavy enrichment for apples around the console table, so but that doesn't matter.  Okay, back to Rudy. Richard, is he here? Yeah, he's here. Richard. He's loading his presentation. Excellent, I will, I sure will. I just, where's Richard? Oh, there you are, Richard. So we have a guest that I mentioned earlier would be joining us and we'll just go right into Richard's presentation. I want to introduce to council Dr. Richard Nakamura who has a long history here at NIH. I can just give you some brief background about him. He's actually had a 32 year career at the National Institute of Mental Health in various capacities. He joined it actually as early as 1976 a postdoctoral fellow, but over the years he assumed a number of positions including being the deputy director of the Institute from 1997 to 2007. I got to know Richard particularly when he served as the Institute's scientific director at a time when I was also the scientific director of this institute. He was their scientific director from 2007 until 2011. I also, during that interval, he also served as acting director of NIMH for 2001 to 2002. But then in September of 2011, he was asked by Francis Collins to move over and become the acting director of the Center for Scientific Review, and which he did. And then he also applied to be the permanent director and was selected into that position. And he's been in that role for a number of months now and I thought it was very, and others, including members of this council, thought it would be wonderful to hear from him directly. And so we asked him to come give an update about CSR, Center for Scientific Review and also give you all a chance to have a conversation with him. So Richard.


Hello, I'm Claude Williams. I am privileged to present the official preparation content of the Certified Disaster Recovering Engineer or CDRE. The course and certification are developed, administered, and delivered by Mile 2. Mile 2 is a global education company with courses and certifications targeted to help professionals develop and demonstrate IT and security skills. The CDRE is one important credential in a robust portfolio of certifications that meet industry standards. The Certified Disaster Recovery Engineer course is delivered in four phases, pre-planning, planning, post-planning, and the course conclusion. In the pre-planning phase, we will discuss disaster recovery project initiation and functional requirements concepts to include business impact analysis and risk evaluation. In the planning phase, we will discuss design and development and implementation concepts including emergency response and operations, IT recovery and resiliency, implementing business continuity planning, or BCP, and awareness and training. In the post-planning phase, we will discuss the critical concepts of testing and exercising plans. The outcomes from testing becomes one of the vectors by which we maintain appropriate plans. Thus, we will discuss plan maintenance and plan execution techniques. At the conclusion of the course, we will discuss some well-recognized cyber attacks that drive the requirements for business continuity and disaster recovery. We will finish up with a brief review that emphasizes those concepts you are required to have well-comprehended in order to successfully pass the CDRE exam. Speaking of the exam, the following details the examination experience. There are 100 multiple-choice questions with only one answer for each, either A, B, C, or D. In other words, none of the questions will require you to choose all of the above or select two out of four answers. The candidate is given two hours to complete the exam. A question with no marked answer is considered incorrect and will be graded as such, so be sure to answer all the questions. The results will be provided immediately upon exam completion. Business continuity planning is one of the major spokes on the business assurance wheel, with business requirements forming the center. Without understanding the business mission, drivers, applicable laws and regulations, and overall strategy, business continuity planning will be inadequate and incapable of providing true business value. With a perspective formulated from risk management and a business impact assessment, a process for continuity, resiliency, and recovery can properly be fashioned for an organization. Since many professionals use terms of business continuity planning ambiguously, let's get the technical definitions of some common terminology clarified for our discussions. Business continuity is defined as the activities that ensure critical business functions will be available, and is manifest in an organization's methodical approach to conducting day-to-day business. Business resiliency is the ability of an organization and its resources to absorb the impact of an incident and continue to provide a minimum acceptable level of service. Business recovery is a small subset of business continuity that manifests as the process, policies, and procedures related to preparing for recovery and continuation of technology infrastructure after a natural or human-induced disaster. Of course, the concepts of business continuity planning have a direct relationship to another spoke on the business assurance wheel called security. There are three main security principles, confidentiality, integrity, and availability, more commonly referred to as the acronym C-I-A. The concepts of business continuity planning directly meet the principle of availability with a lesser regard to integrity. Thus, it is important organizations understand the need to integrate business continuity planning with the security strategy. You might ask, what is a disaster? By strict definition, a disaster is a calamitous event, especially one occurring suddenly and causing great loss of life, damage, or hardship. A disaster can be the result of nature, like floods, severe weather, or earthquakes. A disaster can also be human-induced. In other words, an anthropogenic hazard, such as negligence, errors, crime, or terrorism. In more technical and practical terms, a disaster is any event that causes business or technology function disruption that if sustained could lead to business failure. The disruption could result from severe physical or perceived damage and or prolonged interruption of capabilities, such as a destroyed processing facility, a power outage, a flu outbreak, or violation of regulatory requirements. A critical function of business is defined as a function that if disrupted for a significant period of time could result in severe damage and loss to the organization and ultimately lead to business failure. In other words, critical business functions are the arteries and veins of a business that if disrupted could lead to the organization's demise. Thus, business continuity planning is a matter of business survival, addressing availability and in cases, integrity of critical functions. In 2005, business continuity planning saw growth in organizational awareness, penetrating all the way down to the smallest of companies, as evidenced by Brett Kane's comments that year, the VP and General Manager of Citrix Online. Based on a survey Citrix sponsored, he stated, in view of recent threats to business operations from Hurricane Katrina to the Asian bird flu, we're not surprised that a number of small companies are moving continuity planning higher on their to-do list. Business continuity planning is defined as a proactive planning that facilitates the rapid recovery of business operations to reduce the overall impact of a disaster while ensuring the continuity of critical business functions during and after a disaster. Furthermore, business continuity planning contains specific tasks, activities, guidelines, and procedures required to enable continuous delivery of products and services in the event of a disruption to mission-critical IT systems and application processes. A business continuity program will help an organization maintain the resiliency, robustness, and redundancy of its systems, assets, and services. These business continuity terms can be a bit abstruse, so why don't we take a minute to provide them with some much-needed clarity. The word resiliency is defined as the ability of an organization and its resources to absorb the impact of an incident and continue to provide a minimum acceptable level of service. Robustness is the ability of a system to cope with errors without compromise of its initial stable configuration. And redundancy is the duplication of critical components or functions of a system with the intention of increasing reliability, such as a backup mechanism. A business continuity program provides procedures and mechanisms for prevention, response, continuity, and recovery prior to, during, and after disruption. Business continuity planning is vital to the survival of organizations in the post-911 world. Business continuity planning is included as a fundamental cornerstone of a sound emergency preparedness and security program. Business continuity planning enables organizations to survive disruption, including incidents, emergencies, outages, and disasters, while continuing to deliver their critical products and services. According to that same study in 2005 by Citrix Online, four years after the tragedy of 9-11, fewer than one-third of U.S. businesses say that they are ready with a business continuity plan if a disaster strikes. Yet, 34% indicated that business continuity is more important today than it was five years ago, citing an increased threat of terrorism, natural disasters, and economic fluctuations, as well as greater business volume. This shows that it has taken a number of catastrophic events beyond 9-11 to firmly place business continuity planning in the high-priority category for most organizations. Some of the additional events that formed the epitists for business continuity planning today are the Northeast Blackout of 2003, the Asian bird flu scare, which became news as early as the same year, Hurricane Katrina in 2005, and most recently Hurricane Sandy. As previously mentioned, disaster recovery is a subset of business continuity. Business continuity involves planning for the continuation of critical aspects of business processes in the midst of disruptive events. Disaster recovery focuses on the IT capabilities and technology systems that support business functions. Disaster recovery planning, or DRP, basically addresses detailed guidelines, procedures, and job steps to recover each specific system from a point of failure in order of critical business functions' priority, sequentially or concurrently. DRP is defined as the procedures for emergency response and extended backup operations and post-disaster recovery when the computer installation suffers loss of computer resources and physical facilities. In practice, the business continuity plans are considered deficient if disaster recovery plans are missing or incomplete. Just like physical security concepts, business continuity planning concepts focus on preservation of life as the top priority, then business survival processes and systems. Thus, the business continuity plans must place an emphasis on emergency response to avoid or minimize injury to personnel and then company assets. Emergency response is an organization's planned and coordinated response to a disaster event in an effective and timely manner. BCP and DRP are closely related practices that describe an organization's preparations for unforeseen risks to continued operations. The trend of combining business continuity and disaster recovery into a single term has resulted from a growing recognition that both business executives and technology executives need to be closely collaborating instead of developing plans in isolation. Integration has become essential to meet the requirements of minimizing the impact of strategic and operational risks related to disruption. As mentioned, preservation of life is the first goal in business continuity and disaster recovery planning. Additional goals are to reduce risk of financial loss, improve an organization's ability to recover and restore processes and systems while mitigating the effects of a disaster, improve responsiveness to unexpected events, ease confusion during a crisis, and get people back to their normal work routines expeditiously. Because the risks that are being planned for are usually categorized as high impact below probability, it's hard to gain commitment from senior management. Thus, a business case must be made to justify the allocation of resources. The business case must validate vulnerabilities, express regulatory legal and contractual obligations, detail current status of recovery plans and deficiencies, and incorporate recommendations from experts. Very rudimentary reasoning for business continuity planning is grounded in Ruten's law, which states that when a crisis force is choosing among alternatives, most people will choose the worst possible one. Certainly, we cannot ignore Murphy's law here as well, which states anything that could go wrong will go wrong. Both laws are extremely germane to why organizations should undertake a methodical process of preparing for disaster events. Unfortunately, as evidenced by the operational and financial losses resulting from over a decade of major disasters suffered by our nation, a minority of companies have business continuity plans, and of the companies that do, those plans are neither realistic nor workable, and people will not support a plan they don't believe in. Some serious challenges to effective business continuity planning are, one, lack of senior management support. Senior management will always be reluctant to spend money on low probability events, no matter how high the associated impact may be. Two, lack of time. Staff always seems to be overworked and underpaid. Finding the time to research, design, develop, and implement business continuity components can be arduous and met with great resistance. This challenge can only be overcome when the challenge of senior management support has been successfully addressed. Three, capital expense. Depending on recovery time objectives, recovery point objectives, and other relevant metrics, continuity solutions can be very expensive to implement and maintain. Four, poorly defined plans. Without proper understanding of business requirements, strategy and architecture, and the risk landscape, business continuity plans have little opportunity to meet stakeholders' expectations. Five, lack of training and testing. During a disaster event, people need to quickly move from chaos to some sense of order. Even with written plans and procedures, personnel must be well trained, otherwise the resultant activities have little probability of success. Furthermore, without proper testing, there is little to no confidence by management in the appropriateness and completeness of the plans and the planning process. Six, complexity of technology. The technologies involved in timely response and recovery tend to be expensive and complex. Seven, lack of qualified staff. With respect to the previously mentioned challenge, the need for qualified staff is imperative to successfully implement plans and execute associated tactics and technologies. Such staff can be expensive due to the requirement for prerequisite skills in adequate training. And finally, eight, frustration, lack of direction. Due to the previously mentioned challenges, frustration by management and staff can set in if appropriate direction and objectives have not been established and effectively communicated. Now, let's move into the meat of the course. There are seven widely accepted phases to business continuity planning. One, project initiation phase. Two, functional requirements phase. Three, design and development phase. Four, implementation phase. Five, testing and exercising phase. Six, maintenance and updating phase. And seven, execution phase. Of course, our discussion will begin at the top with the project initiation phase. During the project initiation phase, project requirements and structure are being discerned. The focus at this phase is to understand the background underlining the need for such a project. The project scope, objectives, goals and teams required to address the different interrelated activities of business continuity planning development, implementation and maintenance. The outcomes of the project initiation phase of business continuity planning are to, one, establish the need for business continuity planning. Two, get executive management support. Three, establish a business continuity planning governance structure. Four, create a work plan. Five, report to management to obtain approval. And six, establish management capabilities to sustain the business continuity and disaster recovery program. The reason for establishing a business continuity program within an organization can be as straightforward as legislative, regulatory and contractual obligations to do so. More qualitative reasons for the need for a business continuity program can be expressed as increased liabilities and more time sensitive business processes. As previously stated, business continuity planning is about business survival. Given five businesses that experience a disaster event or an extended disruption, two will suffer immediate and complete business failure and a third business will fail within two years of the event. In other words, sixty percent of businesses that experience a disaster will cease operations within two years. Gaining commitment from management requires a well-crafted business case promoting the benefits of a mature business continuity and disaster recovery program. The business continuity manager should detail how the program maps to the business mission, mandates goals and objectives. Without management's commitment, it is impossible to get adequate resources to establish and maintain a business continuity program. Obtaining senior management's commitment ensures cooperation from all areas of the organization, minimizing possible resistance from departments within the organization. A business continuity program structure commensurate with corporate governance is essential to establish clear lines of authority and accountability as well as responsibility and will enable senior managers to sort out competing interests. Business continuity governance must include some form of a business continuity planning steering committee to allow internal stakeholders a sense of ownership regarding business continuity strategy and high-level tactics. The steering committee, along with other business continuity management, is primarily responsible for development of a business continuity plan policy that defines the characteristics of a business continuity and disaster recovery program including scope, mission and other related policies. Once this project will begin the process of inserting a business continuity function into the organization, the business continuity planning policy developed during project initiation must provide a framework for plan development, recovery strategies and notification. The policy should, at a high level, identify critical services and their related time sensitivity. The business continuity program will be highly visible and a bit invasive to implement. Thus, the need for clearly defined roles and responsibilities from the strategic levels to the operational levels of business, including the board of directors and executive management, the steering committee, the risk compliance officer, business continuity coordinator, disaster recovery coordinator, the IT department, the security function and the other operational departments. The policy should distinctly and unambiguously outline these roles and responsibilities, including how the business continuity and disaster recovery teams and business continuity working groups are to conduct activities. Once the policy has been developed, it must be communicated. Effective communication is critical to business continuity planning, governance and program management. Thus, the policy itself must also define a communication strategy. In this phase, a planning team develops a work plan outlining the activities necessary to implement the business continuity project. The plan must be mapped to the business of the organization and based on the worst case scenarios such as the loss of facility, IT capabilities, communications, operational departments and works in process. This plan assists business continuity management with identifying high level resource requirements like staff, consultants, training, time and software. Once high level resources are identified, budget development can begin with a focus on plan development, planning expenses, post planning exercises and recovery expenses. The plan, including the budget, must be well documented and presented for management's approval. Before the business continuity program can be implemented, senior management must approve both the business continuity policy, which includes the proposed governance structure and the business continuity plan, which includes the budget. Management must carefully evaluate the projected program costs compared to the perceived value of the program to the organization. In addition, management must carefully consider proposed and collateral organizational changes in operations and agendas. Once executive management approves the business continuity policy and the business continuity work plan, the business continuity manager kicks off the project by meeting with key organizational persons to ensure effective communication of roles and responsibilities. As the project proceeds, the business continuity planning team should implement the outline communication strategy with a regular feedback schedule which should 1. Report progress, issues and or changes required on an ongoing basis, 2. Create scope creep and 3. Produce status reports of key elements to send to the steering committee. The success of the program is dependent upon the people that implement the program's activities and capabilities. To enforce adoption and continued support, implementers must feel included in business continuity solutions design. The communication tactics must help to assess people's experience that would be beneficial to the program, help to develop allies, help to demonstrate the program's value to the business and ensure that the goals of the program are consistently promoted. The business continuity and disaster recovery program has a distinct life cycle as illustrated in the current graphic. The illustration depicts general business continuity phases on the inside and interrelated business continuity processes on the outside. A business continuity program must be justified, which can be achieved by conducting both a business impact analysis and a risk assessment. The business continuity architecture is manifest in the business continuity strategy development and disaster recovery planning. Implementation of business continuity capabilities must include training, drilling and testing. As an integral part of business continuity management, capabilities must be reviewed, audited and when prudent, adjusted. As the name denotes, this is a cyclical management function which requires that such a program continue to justify its investment by consistently demonstrating how it is vital to addressing business operations risk. In summary, in this section we discussed, the certified disaster recovery engineer exam experience, the phases of business continuity planning, the reasons why business continuity and disaster recovery planning are important to each organization, the differences in terminology including continuity, resiliency and disaster recovery. The objectives of the first phase project initiation of the business continuity planning model including establishing the need for business continuity planning, getting executive management support, establishing a governance structure, creating a work plan, obtaining management's approval and managing the business continuity and disaster recovery program. Lastly, a high level overview of the business continuity program management life cycle was provided.