 Well, good afternoon, everyone. If everyone would take their seats, we will start this symposium. I'm Eric Green, Director of the National Human Genome Research Institute, and I want to welcome all of you to this modern code symposium, Genomics of Model Organisms and Human Biology, where we hope to showcase for you insights from the modern code project and NHGRI-led initiative. I want to welcome all of you. I hope you're enjoying the lovely, cool confines of this auditorium in the Natural Conference Center, which is far cooler than what is currently outside in the near 100-degree Washington, D.C. area weather. We are here today to celebrate and to showcase the modern code project and, more broadly, to showcase the important role model organisms play in the biomedical research landscape. What I wanted to do in this opening talk, if I can have my slide, is really to set a context for the talks that are going to follow later today and tomorrow. And in particular, what I hope to accomplish if I ever get my slide, and there it is, what I really want to accomplish is really to set a landscape view for all of you, so you can really appreciate the role that model organisms research, especially genomics research, has played and will continue to play across the broad swath of genomics research activities. In doing so, I want to tell you a little bit about the past. And then in particular, I want to emphasize sort of the present as exemplified by a strategic plan that is really guiding the field of genomics in a particular NHGRI in terms of its research pursuits. And then also give you a little bit of a glimpse of the future, especially with respect to the trajectories that we're trying to put in place through our strategic plan. Now, going to the past, lots of places I could start, probably the most relevant one for this particular symposium, and for the field of genomics, of course, would be the Human Genome Project, which began October in 1990. And I dug out a slide that I have been using since I was a postdoctoral fellow working on the Human Genome Project. And the slide really emphasized the fact, it's a slide I used many, many times over the years, that the Human Genome Project, its name was a bit of a misnomer. It wasn't exclusively focused on human, but rather a carefully selected set of model organisms were chosen. Their genomes were sequenced, studied, and then eventually sequenced. And in particular, they were chosen because the unique contributions in terms of insights that genomic knowledge would provide about different aspects of biology. And this group, Security Council, if you will, of organisms really, of course, augmented knowledge we would gain about the human genome through the mapping and sequencing of the human genome. And the Human Genome Project, of course, was remarkably successful in its pursuits, including model organisms. If we take a brief walk-down memory lane, if you will, you would recall the first eukaryotic genome sequence to be established was that of yeast reported in 1997. A year later came the first animal genome sequence, C. elegans, ably led by individuals in the field, and particularly Bob Waterston, that you'll be hearing from shortly, and John Sulston, and really was a tour de force study that in many ways laid the foundation for sequencing larger and more complex genomes, including the human genome. A couple years later came the sequence of Drosophila's genome, and then one year later came the draft sequence of the human genome, this landmark publication in nature reporting the first mammalian genome sequence. And then remarkably just a year later came the publication in 2002 of the second mammalian genome sequence, that of the model organism, the mouse, which has played such a critical role as a complement to knowledge about the human genome with respect to having a model system for doing genetic studies. A year later came the end of the Human Genome Project in 2003, and with it, of course, came lots of activities to pursue new research avenues that were facilitated by knowledge of the genomes of human, mouse, and these other model systems. Now, genomics has gone in various directions with the kinds of technologies and the kinds of opportunities created by the Fruits of the Human Genome Project. The ones, of course, that we focus on here at the National Institutes of Health, and in particular at the National Human Genome Research Institute, are those that focus on health, disease, and medicine. In particular, NHGRI, which is now an Institute, I have been the director for a little over two and a half years, I can tell you that a significant amount of our effort is now focusing on developing a path towards an era of genomic medicine. Medicine would have been tailored to the individual based on genomic information of individual patients. But of course, that's a very long, complex journey. It's one that our Institute will focus on, I'm sure, many years ahead, but we regard that mission as sort of critical for the reason why we sequenced the human genome in the first place. So in thinking about that journey from the base pairs of the genome project to bedside of patients, or if you prefer the metaphor, from helix to health, when the genome project ended, in fact, precisely the day that the genome project ended from this podium, I can tell you, was the declaration of the genome project coming to an end. And at that point, we also unveiled this new strategic plan in 2003, which a number of us, the leaders of the Institute, put together with help from the community. But at that time, Francis Collins, I know, stood at this podium and described the set of activities that would be pursued now with the sequence of the human and other genomes in hand. And one of the initial steps and a key part of this 2003 strategic plan was the recognition that the human genome project delivered a lot of sequence. And it was good sequence, it was accurate sequence, it was important sequence, but at the same time, one of the next steps that absolutely had to be pursued would be to try to understand the function of that sequence, whether it be the human genome sequence as shown here, but really more broadly, we were thinking about needing to understand genome function in general, and that would in particular inform the human genome sequence and knowledge of its functional components. It was really just a short time thereafter that NHGRI decided that indeed a focus effort to pursue this was critically important, and that led to the birth of the ENCODE portfolio, the ENCODE portfolio, which goal was fundamentally to elucidate genome function. The first component of this was the ENCODE project, Encyclopedia of DNA Elements is what that is short for, which as a project focused on getting a catalog of functional elements of the human genome. But even at the earliest stages of planning the ENCODE project, and I can recall because I was involved in the workshops leading up to this, and I even recall the council discussion, our advisory council when they discussed the ENCODE project was a recognition that to really be effective at this, and to really understand the human genome through the kinds of efforts that ENCODE would pursue, we needed a complimentary effort, as has always been the case in genomics as part of the human genome project, for example, with model organisms. And so shortly thereafter, the MODENCODE project was born with a particular focus on flies and worms, but in addition, of course, since then there's even been MODENCODE components that even include mouse. And it's this MODENCODE effort that we're here to celebrate and the MODENCODE effort that we are here to also showcase. Now what I will tell you is much like the human genome project and many major projects that have been pursued in genomics since the end of the genome project, ENCODE and MODENCODE are very much large consortium team efforts that whereby the efforts really only come about to fruition through collaboration, through extensive teamwork, shoulder to shoulder, shoulder on shoulder in some way efforts that just has proven to be critically important. And in many ways, this NHRI is distinct among most of the other NIH institutes in that this is the style of science that we foster and this is actually what we think we do very well. And I think what you're gonna see for the next day or so in a series of talks that really are showing the accomplishments of the MODENCODE project is in fact that consortium-based science is critically important for this area of research. And what I will predict right now is that the majority of the speakers that you're gonna hear from, just look at their acknowledgement slides at the end and just remember this image and you're gonna see the parallels because what you're gonna quickly learn is that so much of what's been accomplished in ENCODE and what you're gonna hear about is MODENCODE really has been massive group efforts that have required expertise of many people, multiple disciplines, coming together with a shared goal and ending up with the accomplishments that are gonna be discussed. So where are we with ENCODE and MODENCODE? Well, what I will tell you is that we shouldn't recognize these as done projects by any means or done efforts. While the sequence looks amazingly simple and in the case of ENCODE, for example, focusing on the human genome and well underway, I am quite convinced we will be pursuing a complete understanding of the functional landscape of the human genome and these other model organism genomes for many years to come. In the case of the human genome, I sometimes joke that maybe at best we have a Cliff Notes version of it, but decades from now we will still be interpreting, re-interpreting all of these genomes. I think you will hear in the talks that will follow surprises that have completely caught us off guard even in the four or five years that have passed in recent days with respect to thinking we understand all the functional and complexities of a genome and recognizing that there's even more complexities there than we had previously appreciated. So that's a bit of the past, but what I want to tell you is a little bit more about the present and in particular, this strategic plan has guided us well certainly since 2003, but several years ago we recognized that especially with technological advances and the data influx that came with those, that new opportunities were on the horizon and it was time to sort of put another stake in the ground, if you will, with new strategic plan and that's exactly what we did in completing this a year ago and I'm hoping that many of you have seen this strategic plan published in the 10th anniversary issue of nature that commemorated the draft sequence of the human genome 10 years earlier. If you haven't seen this strategic plan, it's a very easy URL to go to, you could easily download a PDF and share it widely and hopefully read it critically, but this strategic plan in many ways captures the present and also looks to the future and that's what I want to spend my last few minutes describing to you. For those of you who have not seen this, I also want to sort of set a context again for where modern code and efforts like it fit into this. In this new strategic plan that really guides, we think the field but certainly is guiding NHGRIs thinking about genomics. What we heard from some very helpful advisors and colleagues that we invited into various workshops and planning sessions was that we had an opportunity to be far more specific and far more sophisticated in describing the research activities that were gonna be needed in moving us from base pairs to bedside. And in particular, this could be organized under sort of five major domains of research activities. Some of these were very familiar to us and some of these would be new for us. So for example, one domain of research activity would involve using genomics to understand the structure of genomes, that sounds very familiar. Or in particular a second domain using genomics to understand the biology of genomes while modern code and code fit squarely in that second domain of research activities. Of course, we're interested in using these advances to better understand human health and disease. And so a third domain would be to use genomics to understand the biology of disease. From such insights, of course, one would imagine having opportunities to advance medical science. And so the fourth domain would be to use genomics to advance the science of medicine. But recognizing that not all medical advances lead to changes in healthcare effectiveness, we also needed to take on the responsibility which we are doing into use genomics to demonstrate that you can improve the effectiveness of healthcare using genomic information. So these five domains provide a framework by which we think about strategically the things that we want to accomplish. But let me also point out and the people in the audience and listening through video cast who think like model organism basic scientists as many of you do will recognize that this progression from left side of the slide to the right side of the slide is not the only way science progresses. And in fact, there's a non-linear aspect to associate this and we don't mean to imply otherwise. And by that I mean discoveries in one domain can often immediately yield insights or new lines of experimentation in a non-adjacent domain. And also the reverse order takes place where you can start at the bedside of patients and work your way back. Or for example, insights that you may gain about the biology of a disease might instantly tell you and give you insights about how genomes work and how immediately lead to experiments that maybe you're done in model organisms to provide more deeper insights than one can get by simply working on human diseases alone. And so there's an interplay of these different domains that's very healthy. You just have to, with the way we represent it in a two-dimensional figure, it ends up seeming like it's progressive from left to right, but that's not really the way we mean to imply the only paths. The other thing that's very useful we have found for these five domains is to use them to sort of think back on what's been accomplished over the last 20 years in genomics and also to look forward over the next 20 years. And the way we chose to do that was by simply representing genomic accomplishments that had taken place at different time intervals and then in different ones of these five domains. So for example, we represent the human genome project as an era with many, many accomplishments shown here as these dots first blue and as they pile up on each other then progressively changing color, eventually becoming red. Fundamentally, the human genome project was efforts that led to accomplishments to understand the structure of genomes. Sure, we learned a little bit about the biology genomes, but fundamentally it was the first domain where most of the accomplishments took place. When the genome project ended, we continued to explore the structure of genomes, of course, but through efforts like ENCODE and MODENCODE and many others, we began to explore and understand much more about the biology of genomes, leading to many dots filling into the second domain. And sure, some advances took place in these other domains, the disease specific domain in the middle and maybe even a few accomplishments out in the more clinical domains, but fundamentally the activities in the past decade or so have been the center of gravity resides in the first two domains. Thinking about the future, well, the future we think first over the next decade or so is gonna see a progression of accomplishments so that the greatest accomplishments we think are gonna reside in the second and the third domain. In particular, as I alluded to before, we have a lot more to learn about genome function and we think a lot more is going to be learned in the next decade, but we also think at the same time this is gonna be a decade of great excitement as advances really do lead us to greater insights about the biology disease. With that will certainly come more accomplishments in the more clinically oriented domains in the far right, but realistically we think the greatest accomplishments in those more clinically more difficult domains and thinking about the things that need to be done realistically are not gonna be happening as much in the next decade as we'll be taking in the decades beyond then. So there's another subtle feature though that I also wanna point out, actually before I do that, let me just also point out to you and you're gonna see this play out in multiple of the talks you're gonna hear is that what is driving this forward over the next decade and in particular beyond that, probably more than anything else if you ask me to name one thing, one issue, one factor that is driving this progression from the left side to the right side. What I would tell you it almost certainly has to be the dropping costs of sequencing genomes. And so in particular, for those who don't think about these numbers, let me just give you a flavor and then we'll try to extrapolate that to what this means for model organisms. If we think about just sequencing the human genome, when we first sequenced that very first human genome as part of the human genome project and when we actually were actively sequencing it took something like six to eight years and cost something like a billion dollars, especially if you round up but that's around the order of magnitude we were dealing with. When the genome project ended, people sort of did some calculations to say just today, the day the genome project ended we went back and tried to sequence a second human genome. The predictions at that time were using the technologies available that would take something like three to four months but still would cost 10 to 50 million dollars. I don't need to tell a sophisticated audience like all of you what has transpired in the last five or six years in terms of these next generation sequencing technologies have been just truly mind boggling. And what's happened now is of course today in the course of maybe a day or two or three for a cost of maybe four or five, $6,000, you can get an entire human genome sequence. Truly astonishing reduction in the cost of sequencing. But then think about how much bigger the human genome is with respect to the genomes you're gonna hear about in this symposium, worms and flies and so forth. And with their much, much, much smaller genomes the cost for sequencing their genomes is just ridiculously small. And what you're gonna hear therefore are some remarkable studies probing genome function because the same methodologies that can be used for sequencing human genome can be used for not only sequencing model organism genomes but as readouts for all sorts of assays that are used to be able to elucidate genome function. This has really driven the encode and the modern code projects forward and you're gonna see how some of these applications are gonna continue to drive these forward because these remarkable technological advances. Very last thing I wanna point out though is that this figure from our strategic plan which is figure two, it's the organizing figure in many ways this is the icon that I can tell you NHGRI looks at and thinks about in developing programs and thinking about our strategic planning going forward has some subtle feature that I think is very relevant to this symposium and by that I mean if you notice it's not all the activities that are gonna deal with diseases and with medical science and with healthcare and in fact if you notice over the next decade and even a decade beyond that a significant coloration if you will of accumulated hypothetical dots of accomplishment a remain in the second domain and the third domain and I can absolutely assure you that the reason we are thinking in those terms is the recognition that so much of understanding the biology disease and so much at understanding the biology of genomes especially when you get to some of these key mechanistic aspects of disease and of genome function are simply not going to be fully elucidated by studying the human system and by that I mean there will absolutely continue to be a key role of all these model systems shown here and probably others and the interplay of these models with what we learned from humans but inevitably we will be looping back and having to use model systems to really understand human disease mechanism because realistically the limitations associated with human systems are so profound compared to the genetic manipulation one can do to these models that we recognize that in so many ways these are gonna continue to be so incredibly important and then think about how the genome sequencing technologies in many ways democratize the ability to study these genomes and how much simpler they then are in the case of worms and flies and yeast and so forth that one could imagine that this not even just being an endeavor that NHGRI is thinking about but indeed as these various disease studies are taking place across all the institutes at NIH and their disease specific areas that the same interplay of genomics model organisms and disease understanding will become sort of just a commonplace as science marches forward. So I really wanna emphasize as you listen to your the talks in this symposium that recognizing that many of these dots that remain over the next 10, 20 years in that second and third domain very much apply to model organism accomplishments. So lastly I wanna point out that NHGRI is holding this symposium but of course symposium tablets don't get pulled together without hard work of staff. I wanna acknowledge in particular the four people at the top, Carolyn and Mike and Leslie and Elise who have put in a tremendous amount of work to organize this. In addition to the people sitting in this room this is being video cast live to probably many people around the world oftentimes we find we will also be video archiving this and featuring and making it permanently available on the genome TV channel YouTube that NHGRI now has and I can tell you from experience that when we put on symposium like this and bring in all star speakers that are gonna follow me that indeed we get just tens and thousands hundreds of thousands of hits and so this is sort of for the permanent historic archive but it will absolutely be used actively in the coming weeks and months as many people who can't be here today I'll be listening in about these fascinating and important talks about Madden code and also I wanna thank the individuals in the bottom who are some of the individuals associated with our contracting group who helped facilitate some of the logistics associated with this symposium. So with that I will stop I will thank you for your attention and I hope this was a valuable context for you to now hear the rest of the symposium and with that I will turn the program over to Elise Feingold.