 So, what I would like to start up with today is what next? What's the National Human Genome Research Institute after the Human Genome Project is completed? And how did you think about the transition from doing a project to next things that are important to do? Well, having the draft announced in 2000 was a milestone, but maybe scientifically, more importantly, having the publication on the draft in February 2001. It was pretty clear at that point, we are going to finish this. We're not going to leave it as a draft. That would be unfortunate. As in most things, the last 5% is about as much work as the first 95%. And that was certainly the case. So there was an awful lot of work to do there for the next two years, until 2003, where we basically said, OK, we have a complete human genome, admitting at the same time that there were bits and pieces of it, like centromeres, that had not been completed and still have not, because of the nasty nature of those DNA sequences, just preventing you from being able to assemble them. But just the same. It was a moment, April 14, 2003. We had this event in the Library of Congress. We said, OK, we've really, really gotten to all of the goals that were put forward for the human genome project 13 years earlier. So it wasn't just that we have the first reference human genome sequence. We've also accomplished all the other things that were part of that effort as laid out by the National Academy original blueprint. So it was really a moment. And you might say, well, then we should all fold up and go home. But obviously, that would have been kind of leaving the good part unattended to, because this was laying out a foundation, and now you had to build on it. And knowing that was coming, we had spent something like 18 months really working hard on sampling all the bright brains out there about what would be the next appropriate goals for the field of genomics, not just genome sequencing. And where should we place the resources and place our bets in terms of what the Genome Institute could do to keep that momentum going or even accelerate it. And that was a bunch of workshops. And one very large meeting at the beginning and a lot of workshops. And then another large meeting at the end that sort of pulled this together, ultimately a document that laid out what the plan was going to be published in nature. So we made it very clear, here's what we think is next. And that was published simultaneously with saying we have now completed the goals of the project. And it needed, of course, a visual that I was struggling with what that should be. And I went to a boarder's bookstore to sort of look through books of various kinds of images and happened across a book of falling water, Frank Lloyd Wright's most iconic structure. And that was like, oh, OK, we could do something with this. And so there it was as figure one in that paper describing the future of this building, which had three levels, but it also had cross-cutting elements. Maybe it was helpful. At least I used it for the next two or three years to kind of explain the various areas that we were trying to nurture. And out of that came a lot of what came next, although some of it already started. I mean, we knew that having a reference human genome was nice, but the 0.1% variability in the well-behaved part of the genome was intensely interesting. And we should start looking at variation. And we had already started doing that well before 2003. But HapMap kind of as one real flagship next effort was clearly part of where to go next. And we wanted to understand function. And that's the motivation behind putting together the idea of ENCODE, the Encyclopedia of DNA Elements, and how we could, by building on lots of laboratories that had lots of capabilities in challenging cooperative agreement kind of mode, begin to understand what were the parts lists, what was the parts list of the genome, and how do those parts make sense in terms of regulation. There were other really important parts that related to ethical, legal, and social issues. We had not solved any of those as definitively as we would like, obviously, especially genetic discrimination. There were lots of issues about advancing technology and not wanting to stop with DNA sequencing abilities we had in 2003, because we knew one genome for $400 million was not going to be a good long-term solution. So all the more reason to put effort into dropping the cost, increasing the speed while not sacrificing the accuracy, all the things that really played out beautifully then over the next 10 years and continue to in terms of making sequencing ever more accessible and affordable. So Francis, the politics of this, one way of taking that is you've gone from having a difficult problem of getting a whole bunch of people to work in concert for this incredibly big international huge goal and a huge public event for announcing success. And now you've got a whole series of projects and an institution that is driving science in genomics. And your role as the NIH director sounds like it changes a little bit from trying to get to the goal line and being the quarterback to trying to figure out four or five different games that are going on simultaneously. Is that a fair characterization? In some ways, yes, because certainly something like ENCODE had a very different set of ideas and needs as far as pulling together a collaborative effort to look at the functional parts of the genome. HapMap, on the other hand, had a lot of the same flavor as the sequencing of the genome. It was international. It required a lot of coordination and Friday morning phone calls. It needed a field general. And once again, that was me with lots of help from colleagues and other places, especially the UK. But that had many countries involved and everybody had to agree to certain standards about quality and timetables and data release and all that. So HapMap in many ways was sort of a natural follow-on and it was also a sort of natural building on what had worked in terms of how to make such a collaborative effort successful. So that was pretty familiar territory, also pretty exhausting. And we had some different players in HapMap than we had had in the sequencing, which made it interesting because some of them hadn't had the experience of the sequencing project and were maybe not quite sure why they should give up their autonomy to be part of something of this sort. So Eric, you had a question. Well, another comment I was going to make, which I think is relevant for sort of I think an inflection point of the Institute that took place slightly before and then in 2003, I think had a lot to do organizationally due to the following reasons, especially the leadership team. And that 2003 plan came together in a slightly different way because of a different core leadership group. You know, 2002-ish was about the time that Elka Jordan retired. Jeff Trent left as a scientific director. And that gave opportunities for a little bit of shuffling around. Francis appointed me the intramural director, the scientific director. Mark Geyer became the extramural director. And then Alan Gutmacher became the deputy director. Exactly. The three Gs. Which I actually refer to the three Gs. And what I think was important was that 2003 vision that was published in Nature the day the genome project ended, and that 18-month or so process that Francis described was very much of a committee effort. He really delegated to us a lot of responsibility for seeing this planning process go on, which really made it a trans-institute planning process because intramural was as involved as extramural and having Alan as the deputy thinking about issues that complimented nicely what Mark Geyer and I could bring to it. And so that document was affectionately sort of the three Gs plus Fc was sort of the internal abbreviation for it. Exactly. And I also think then leading on beyond that, I think Francis turned to not only the three Gs, but lots of other good leaders within the institute to really help him more on individual projects. Mark Geyer and I went off and really helped, I think, develop some of the early blueprint for encode. Alan certainly went off and helped on some specific areas. I think it was a more distributed effort, which gave him the opportunity to decide where to spend more of his time knowing that some of the other trajectories were taking good care of. So let me stay on that for just a minute because I'd like to pull out kind of the signature of this National Human Genome Research Institute. What is it that's distinctive about it relative to the other critters here in the NIH forest? Yeah. It seems like there is an element of planning and anticipating where the science is going and systematic staff work, the politics, the leadership. Talk a little bit about top down versus bottom up science and what's the distinctive role of this particular institute compared to its brethren here? That's a good question because certainly by this point every institute is investing in genomics one way or another. The technology has gotten distributed not necessarily at scale the way it was in our large-scale sequencing centers, but certainly many labs were taking a lot of advantage of the success of the genome project and that was good. What was the unique niche then for NHGRI? It was about this time. I think the IOM came out with their big description of what should happen to NIH which had a number of recommendations that might be considered, none of which have happened in terms of shrinking the number of institutes and maybe NHGRI ought to just sort of wander back into NIGMS and be absorbed in that space. Obviously that didn't happen. But it was it was crucial that NHGRI continued to serve and to serve they had to have some unique kind of role and I think the unique role was genome science at scale because other parts of NIH were really not prepared to do that. Now that doesn't mean it's all top-down. That means you want to induce very bottom-up technology that will improve the scale and so getting for instance DNA sequencing to go faster and better cheaper. I wouldn't say that was top-down. There's a lot of really incredible creativity going on in academia and in small businesses that Jeff Schloss brilliantly nurtured along and look where that's gotten us. But some of these were production projects to produce community resources that should follow Bermuda rules and therefore be immediately accessible and you don't see those happen unless there is an organizing force and that was sort of one of our visions of what NHGRI could continue to do whether it was for ENCODE, whether it was for HAPMAP, whether it was ultimately for Cancer Genome Atlas only a couple three years later, whether it was a knockout mouse project which was also very much something that got pushed forward from the Genome Institute or even whether it was and this was maybe the furthest departure from what had been our sweet spot, the establishment of the molecular libraries program as a means of trying to put into the hands of academic investigators high throughput screening capabilities for small molecules so that they could in fact go from diagnosing to thinking about treatment and that was a personal strong priority for me is to make sure that that opportunity didn't get missed and this came along at the point where Elias Zerhouni had started something called the road map to try to find ways for funds to be collected that would not necessarily get spent by any single institute on a project but could benefit everybody. That was timely that he had that vision that certainly turned out to be a way of extending the genome institute's ability to influence some of these game-changing projects that were large-scale expensive and beyond our own little budget. I mean we had many opportunities after 2003 and even more recently to become more normal relative like all the other institutes and centers. I think there's a certain cultural flavor of the institute, I think an expertise level at this is to be pioneers in the way that science is done. Now that is a model for doing science. I don't think we've ever said it's the only model and it's probably the unusual and the rare one. I don't think every institute should be like us by any means but you know we clearly did something very different in the genome project and the projects the genomics projects that immediately follow the end of the genome project and they continued to receive good feedback about their reports. I think what they produced was valuable and I think the way we led them was was key to their success and also proved to be an effective way of leading some types of science. Now what does that get you by the way? It gets you more work because what it means is that when you're that rare institute or institutes that is capable of leading these efforts and then other opportunities come up. Common fund examples what Francis just gave are the good ones. You're asked to to take on a lot of that and carry a lot of the water because you're good at that and that's fine and I mean we embrace it and we prepare for it and and we are as much to blame because we propose ideas that are bigger than our budget but are well within our intellectual capabilities and our leadership capabilities and then when these ideas actually get approved that means we have to actually do something. Do something and find this out. So that's why yeah it's right so I mean we end up being overachievers I think in many ways at the corporate level because of the proven track record of leading these large projects effectively. So a lot of this involves high tech was bang instrumentation and data and computation that's part of the signature. One other thing though and we talked about it in the last interview briefly but I didn't talk about one I didn't ask the appropriate question about one part of it that I think is really worth clarifying DNA sequencing the core technology you get this reference sequence all over you don't need to do anything more with technology right you've got your reference sequence. Well no this institute was heavily involved in almost a DARPA like. I mean I think people would say without Jeff Schloss the world would have been a different place and there was leadership anticipation and that's kind of a you can't force that kind of technological innovation to happen from the top. You can provide the resources that enable it and the vision that feeds it when it's about to make a breakthrough. So how do you guys think about that that's a different style of thing and what were the there must have been some explicit thought about what you were doing to push DNA sequencing technology per se. There was and as early as 2003 we started talking about this mythical goal of the thousand dollar genome and it helps I think to lay out a goal that seems almost impossible to achieve to get people electrified by what that would mean if you could do that. So that was part of it making it clear that we are not satisfied with where we are not by any means we've got orders of magnitude that need to be crossed to get to where we want to be and there's no reason not to get there so let's be creative and let's put a lot of money into the technology development to encourage wacky ideas. If they have any chance of success we're going to lay this out in a DARPA like fashion that we expect failure to be extremely common as long as there is an occasional success we consider this as money well spent. The other thing we did and we should have mentioned this already is by making big investments in comparative genomics okay we've got the human but now we've got all these other species that we want to look at and we want those to be high quality genomes so that we can really do as Eric Lander liked to say look in Evolution's lab notebook and see how every nucleotide has been affected by evolutionary forces that presented the concept of a huge market for sequencing machines because we were therefore talking about many many many genomes of different species and we were going on with HapMap which you're not going to find variation unless you do sequencing so we were creating a demand by making it clear that NHGRI was going to be spending a significant fraction of that half a billion dollar budget paying for sequence and therefore anybody has an idea about how to build machines that are a little bit more competitive than what's out there they're going to find a pretty receptive market. So all the pieces I think were in place and I think it's fair to say at that point maybe the government was the main driver of the technology advances these days as this has become more and more something that private sector themselves wants and invests in I think that momentum has gotten to the point of being sustainable even if we weren't making such a big push but our push is still awfully important for the early stage ideas. What's kind of the biggest surprise of where that's taken you this ubiquitous relatively low-cost sequencing technology stuff that you just didn't see happening that wasn't part of your five-year plan or a ten-year plan or whatever. Microbiome would be one of the things I would immediately list and the speed with which microbiome research not only became an entity and a recognized and respected field of study but seen it happen so fast that it sort of distributed so effectively across the NIH the different institutes that you almost don't even need a centralized effort. We did the human microbiome project and now we're winding that down and it could be wound down because it was so clear that it was getting taken up by all the individual institutes. I mean that happened much faster than I ever anticipated. That's one example. I would agree cancer I remember having a conversation with our sequencing center scientific advisors and I don't know was it 2002 it was probably around that time and proposing well maybe if we can drive the cost of sequencing down we could start actually sequencing individual cancers and finding out what's driving them and at that point Janet Raleigh was one of our advisors and she was like that'll never work you won't be able to make any sense out of it there'll be all this noise from because cancer cells are mutating all the time and she was strongly opposed which was pretty interesting it took me back a bit she came around obviously as we began to figure out how you would do this and that yeah one cancer sequence was going to be impossible to interpret but if you had 20,000 of them you could start to figure out what the signal was and what the noise was and that's pretty amazing that we got there in the space of well eight five or six years after having that first human genome we were deep into cancer. So one other thing that happens when you've got this reference sequence and you've got this now signature of hi-tech was bang data intensive that's your style is the other parts of NIH and the other parts of the world and the other parts of the research apparatus beginning to see the value in what's emerged from this huge project and are beginning to want to play in that sandbox that changes the role of this institute because it means there's a connection to all those other pieces what does that begin to feel like presumably that transitions beginning to happen even before the reference sequence is announced but certainly after that I think it's been mostly a good thing as long as everybody's playing by the same rules about data quality and data access I mean take the thousand genomes program which has been obviously a huge contribution to understanding variation at the most detailed level I think it's fair to say the push for that came a little more from the UK than it did from the US the initial sort of vision of this particularly from from Richard Durbin and obviously with a lot of organization that went along with this effort that we were a big part of but that seemed okay to me that we don't have to drive every part of this I'm sure we're going to talk about BGI here in a second because here here is a remarkable center in Shenzhen that at least for a while had the largest sequencing capacity in the world I'm not sure they do because they haven't now kept up with the newest machines but was that a threatening thing it was to some people I suppose and it certainly was a surprise to people who thought the US would remain dominant for centuries to come it wasn't that hard with some energy and some funds for BGI to jump out there and create an amazing center with amazing talent again I never felt like that was such a threatening outcome as long as they're playing fair I think the the issue of NHGRI's relevance relative to the rest of NIH as genomics spreads across the NIH you know really became important to consider the talent of Francis's directorship and then in particular when I became the director and in fact immediately when I became the director we tried to do portfolio analyses to sort of get a handle on you know how much money or other institutes spending in genomics and those are hard data to sort of come by exactly what he defined as genomics but it became pretty clear that by the time I was the director of the institute that there was more money far more money somehow being associated with genomics research being pursued by other institutes compared to us we were the minority genomics funders and that does make you pay attention to define your relevance you don't want to be doing with you know what everybody else is doing that becomes a fun challenge I don't think that becomes a threatening challenge I never took it as a threat but I do think the 2011 strategic plan which was the one that we finished on my watch the planning process started on Francis's talent of his watch I think the 2011 plan more than any other plan clearly laid out a vision for what genomics needed to be but also completely acknowledged that this was a vision that all of the biomedical research enterprise should be embracing and that within it NHGRI would clearly you know pursue some things harder than others but we would do everything we could to stay at the front pioneering out of it because that's always been our strength so Francis what do you think having been director of this institute had to do with your becoming the director of NIH and then both of you talk about this transition because you're now the former director of this institute but you're the top gun now at NIH and Eric becomes the director of NHGRI well I would not say that becoming director of NIH was part of my life plan at all it's not like this was okay I need to step out of this one in order to be asked to do that one by a time it got to 2008 I'd been in this job for 15 years of leading the genome institute it had been a great ride a lot of really cool things continued to happen but I was getting restless and feeling like I probably have something else that I might want to do but I don't know quite what it is I really wanted to write a book about personalized medicine and couldn't do that in my government job because it would be an overlap with my official duties and I was just restless and ready to try something else so I went to Zerhune and told him I was ready to ride off he tried very hard to talk me out of it shortly before he quit himself by the way which was interesting and then August 2008 that was sort of okay I'm walking out as we said into the white space not knowing what I was walking into because I had no other job lined up and I did not know that that would result ultimately in just about exactly a year being called back in a different role but so it went I was frankly quite excited about the prospect of Barack Obama as a president who cared about science so I worked on the science committee for his campaign and then once he was elected I worked on the transition team with Harold Varmas to try to be sure that everything was ready for inauguration on January 20th and I don't remember much about Thanksgiving and Christmas in 2008 because it was completely consumed by those transition activities but then inauguration day came I stood out there like everybody else and froze to death while waiting for the events to happen and figured okay did that now I better figure out what I want to do next and didn't expect really that there would be then a call from Kathleen Sebelius to say I want you to come and talk to me about this job but hearing from her and then hearing from the president that this was what they was hoping I would do it's pretty hard to say no and it was an exciting way to sort of broaden my own opportunity for a landscape surveillance and maybe bring some of the skills from the genome experience but also have a chance to learn a lot of new ones so in a way it's bringing the old team back together because the two of you used to hang out in the old nurses quarters right and when you were both starting your new jobs now you're on the transition team and in a way you're now the NIH director and he's an institute director we did yeah we did a randomized crossover trial and Eric for you how does this you become stepping into the shoes in a way of of Francis Collins yeah and big shoes talk a little bit about the succession of Watson Collins green yeah I don't know how green got in there that's a little intimidating um big shoes to fell but you know one of the things I would immediately point out is especially at the stage of becoming the director of the institute I think my assuming the Raines the Institute it was a very different circumstance than what Jim and Francis had yeah and and the reason for that is that you know when you and you explored this with each of them I mean when they were brought in in each case it was to run a project it was to run the human genome project that was the major focus when they arrived on the scene and you know when I was asked to become the director I was asked to come in and run an organization and I was asked to nurture the growth of a rapidly maturing field and that's very different circumstance than what what Jim certainly had but even what Francis had and I you know I think about what I had to do you know both organizationally and programmatically I mean organizationally it really was time to look at NHGRI in the current context of what was going on in genomics and how we were nurturing and funding programs and realizing that the structure of the organization had not changed since the human genome project and clearly the field was different we were different as an organization I would also say there was issues of transition at the leadership level and I had a I had to assemble a new leadership team because people were moving on or telling me they were getting near retirement and so forth and so I had to do a lot of changes to the institute organizationally and leadership-wise and to be honest with you that at times proved challenging I mean I think I just put my head down and said I'm gonna do this but there was some consternation to be honest with you by some of the people surrounding Francis in the leadership position being a little worried that why is this new guy going and tinkering with this institute that the NIH director used to lead I mean did he not know how to run at institutes so now it was why was it such a fixer-upper you know and I got a little bit of pushback every once in a while about some things but I mean it was never from Francis and in fact I think I told him about almost everything I plan to do in renovating the place and you agree with it and you all agree with it and in some cases you even said you know that probably was overdue I wasn't going to do that at the tail end of my directorship and it all made sense but you know so organization there was a lot of and I I just think in in Jim's case and in Francis case the laser focus was we just got to get this human genome project to be successful so I'm not saying mine was harder or theirs was harder was just very different I also think programmatically it was there were a different set of challenges that I had a face one we've talked about a little already was really better defining what was NHGRI's place on the NIH in particular landscape because everybody's doing genomics what are we doing unique that was never an issue earlier for Francis or Jim I think the other thing that I face I certainly felt this quite strongly was my main push early on is as visualized in that 2011 strategic plan was to start to move the Institute's research focus extending it beyond basic genomics and start to think about clinical applications and I walked into tension it's the classic tension between basic research and clinical researchers and and that's something that other institutes had been dealing with for decades but I was facing it not only with my internal staff I was facing it with my community some people being very against that or you know some people feel and I was going too fast others that I was going too slow most people were pretty unhappy what I finally concluded was these issues I was dealing with both organizationally and programmatically these were middle-aged problems that's what institutes have to go through when they're middle-aged and and Jim and Francis got to preside over an institute in in youth and adolescence and they didn't have to deal with a middle-aged institute which I I had to deal with and I continue to deal with it's just a different life phase of the organization so could each of you talk about one of the signature features of NHGRI has been a strong association with open science with a particular style of doing science that is we share we get stuff out as quickly as we can and we get it as broadly available as possible talk a little bit about how that works and what you see is the signal events obviously the Bermuda principles is one of the landmarks there but many many other steps so talk about how you think about that strategically as the directors of this place I'm glad you brought it up because I think in the view of long-term sort of historical contribution I think the open science attitude which was born particularly out of those conversations in the genome community is one of the most significant contributions this whole effort has made and has now spread into many different areas of biomedical research and certainly now as NIH director I see the evidence for that all around me of people saying you have to have your data sets available we're making that now a requirement not just for things like sequencing the human genome but for all manner of science that people are doing and it's it's become the norm it's sort of the the ethical standard is that you don't hoard your data you make sure that it's as accurate it can be but you put it out there and it's revolutionary in terms of how it empowers all of the bright brains that are out there to build upon what's being developed it's crowdsourcing in in the most appropriate positive way and all of that sort of going back to that day at Bermuda which I think we talked about before which arose and it might not have because the people who were there making those decisions had no real authority to do so but they did anyway on the basis really I think of of a moral argument that you're taking dollars that people have contributed to this effort to a public program and there's no justification for not putting the information out there so that it can be used for ultimate human benefit but we had Fort Lauderdale after that sort of the next go round of okay that now is the norm for DNA sequence but what about other kinds of large-scale data and the idea of a community resource project and the fact that if you were doing one of those you better make your data available the same principle applies that was a tumultuous meeting that almost fell apart but actually kind of got grabbed out of well on that point does it feel like we would have ended up at the same place anyway or does it feel inevitable or does it feel like something that was highly contingent and I you know obviously a parallel universe where there was no Bermuda would be interesting to see I think ultimately the case is so compelling for public good and I do think public good drives decisions eventually looking at our congress right now eventually seems like it could be almost infinite but for this kind of argument to not have reached this point eventually it's a little hard for me to imagine but it might have taken a decade or more to get there and a whole lot of hoarding might have happened and progress might have been impaired and science would have I think suffered and the public would have suffered so yeah I think it mattered a lot I think it was a huge part of why we all look at what the human genome project did and say that really changed everything and how many other institutes thinking about this the same time that you all were doing your reference sequence were they drifting in the same direction is what's your sense about that occasionally you know some amulated some I think sort of said yeah it's not practical or I don't I've got too many other things to deal with I don't think there was a universal commitment here's one of the points I would make because I might agree with Francis that eventually we might have ended up there but I'm going to tell you you know I I took over as director a little over five years ago and one of the things I inherited was a process to generalize data sharing across the NIH for all genomic data because they had gone from sort of Bermuda principles to Fort Lauderdale principles to principles for sharing genome-wide association study data for example the GWAS policy and it just started a committee process trans-NIH to get a conversion from GWAS data to all genomic data to be shared by policy across NIH intramural extramural and make it sort of so universal which I think is just so obvious the resistance the inertia to give so I think if we didn't continue to put huge energy into this you know Laura Rodriguez and I subcommittees and subcommittees and subcommittees of just you know carrying very heavy stones up a mountain weeks and weeks and meetings and meetings here we are in 2015 and we're just five years later we are just rolling out this NIH wide genomic data sharing policy I know for fact I can tell you that if we hadn't been carrying these stones up the mountain it was not going to happen in 2015 I'm not sure what have happened by 2020 so I think you know NHGRI and other converts that we have and I think we have far more across the NIH now than we had five years ago absolutely have to put the in it we just it's not a matter of if we're going to do it it's just how working out the mechanics how would you get this written into grant language how do you what are the legality it's all those operational things and it does take time and there is resistance and and and there's many micro examples where we've seen genomics communities merging with disease research oriented communities and we just say well of course we're going to share the data and there's pushback so I I don't believe it would happen nearly as soon if it wasn't for the push that started in Bermuda but that movement continues and we're not letting up and people could see it really made a difference it did result in more rapid progress and that created sort of a delightful contagion where other kinds of data that had not been made public now people began to ask well why not look at clinical clinical trials data I mean here we are having just put out this notice that all NIH funded in fact all us funded research in clinical trials is going to have to release the results in summary form 12 months after they collect the last data point shocking to imagine that and shocked a lot of clinical researchers to realize this is not just a suggestion and this is a requirement that I don't think we would be in that space with that kind of data if we hadn't first shown with genome data how valuable it is to just get over it this idea that you can hang on to your data for indefinite periods of time until it suits you and you grew up in human genetics where that clearly was not the norm well you could say that yeah the human geneticists were not exactly role models in many ways there were some of the worst offenders in terms of unwillingness to share samples share data share anything in fact in a way the two of you represent a generational shift with human genetics and then you're growing up at one of the epicenters of yeast and nematode biology that is this open science we share everything along the way I'm glad you mentioned nematode because I do think what was done with cl against was a really important sort of setting the stage and when we had that Bermuda meeting it was Sulston and Waterston who were particularly powerful in convincing everybody that you have a lot to gain by immediate release and you have no way of justifying the alternative so I wanted to we're getting near the end of time and I want to actually ask each of you kind of here's your chance if you is there a part of this story that just doesn't feel quite right in the previous accounts that are out there in the world are there things that um you wish the world knew about or go another direction what are the things that you think are most memorable or most significant about your respective periods as the as the directors of this institute I guess what sticks in my mind most is the ability to pull some of the most creative energetic brilliant people who would have been doing something else together to work as a team on these projects and uh yeah I do remember sometimes where that was not easy and difficult conversations had to be had but mostly I remember how impressed and inspired I was by how people who could have demanded to get all the credit because they had the skill sets in any other field that that would have been likely to happen they were willing to say no no the goal here is what matters we're gonna do this together we recognize that nobody succeeds unless everybody succeeds and have a chance to participate in that culture change for science because that hadn't really been done in life sciences before that I'll remember and now you see it happening much more readily but at the time it was pretty radical uh it was inspired what would be the story that you would tell that would most exemplify that that cultural norm shifting is that is that the reference sequence itself or is this other project that you're thinking about in that kind of collegial you know it's all of them but maybe for me especially because the sequencing and half map were ones where I really was in that role of trying to keep the team together and and that was not easy I mean in the dark days where congress was questioning whether there was a need for a public sequencing project anymore and the private project was making lots of claims about what they had accomplished but nobody could see the data so we were sort of at a disadvantage because our data was all out there and you could see what was done and what wasn't uh there was a particular moment where the public project leaders really were beaten down and almost ready to say maybe we should just say let them do it out there and eventually maybe the data will be public and maybe that'll be okay that was a very intense Friday morning and I knew that was coming and I had stayed up all night thinking about how to make the right kind of points about why this was historically so important and why yet wasn't fair the way it was being portrayed but why everything that people had worked for was actually on the brink of working because this was at the point where we were just about to really take off. Is this like post hearing in the house so may salara announces July the hearing happens is this in the wake of that hearing or a little it's six months after that with the sort of constant barrage of PR coming at us and many questions informally coming at us from the Congress about why are you still there that was uh challenging time but people got it and needed to vent a little bit and uh because my gosh these people worked so hard I mean what we went through uh trying to ramp up to a thousand base pairs a second seven days a week 24 hours a day from where we had started and constantly having to revise and make a new plan because the technology came along to make it so I mean what we put those sequencing centers through month after month just when they thought there was like a trajectory and then it got shifted again and they had to retool amazing dedication. On a whiplash I remember I mean I watched this because I had a fairly close view and it was a lot of whiplash but they seemed to tolerate it because of the laser focus on what the goal was and a willingness and it was a goal not just to say we did it but we gave it away. You know one of the untold things it's not a specific example but it's a pattern and I find especially as I talk to young students and trainees especially those who were like not even born when the genome project started and there are a lot of those now aren't there are read about the genome project and and projects like it and just think that there was this playbook on day one exactly what we were going to do yeah right there is I think one of the untold or maybe misunderstood perceptions of these large genomic initiatives whether it's the genome project whether it's hat map whether it's encode thousand genomes etc etc etc I mean whether it's precision medicine whether it's just this all and a lot of common fund projects along the way human microbiome project and so forth is the idea that when they get announced and even when they first get funded that there is just a clear path of what we're going to do and you know and I joke about thinking back in the genome project day one you know there I am a postdoctoral fellow in Maynard Olson's lab and you know we were terrified we had we had no idea how we were going to do any of these things and we had audacious goals both at the project level but what you're funded for but also the big project level but it's true for every one of these things is that you start and you really have no idea the fact that we put our names on a paper you know in 2003 that said we're going to get to a thousand dollar genome and if you would have asked any of the authors of that paper the three g's or fc you would have asked you know how are you going to do that we would have said we have no idea you know we have no idea and yet I think I think students will read look back on that and say oh yeah 2003 they laid out a plan for getting to a thousand dollar genome and they followed the plan and there they got to be but it's this it's a it's a consistent pattern with every one of these things you just simply lay out audacious goals you say a few things about how you're going to get started to reach them and then you figure it out and I got to say the irony of having this conversation on this day this is January 29th 2015 tomorrow morning there will be another audacious program laid out by none other than the president in the east room of the white house same place is where that announcement of the draft genome happened 15 years ago and again it'll be an audacious program where the details are very unclear and maybe people assume that we know what we're talking about well in general terms we do but most of what really has to be worked out is going to have to be worked out as we go along that's why it's fun actually you have to have nerves of steel though you're willing to announce audacious things and say you're going to achieve them and having no real idea at a detail level how you're going to do it but I think I think this institute and increasingly NIH has this track record this works and I think part of it is and I think it's the spirit that Francis was speaking to about the participants the Human Genome Project was that when you can point to a goal and you get people believing in it that they're willing to sort of come together and be flexible and nimble because you have to be and they'll rally around and work together to achieve the goal that's the genome way so the the high point slow points you told us a moment Francis and I appreciate your sharing that kind of that low point moment what are the compensatory euphoric moments that you guys can think of that are associated with with running this place a particular moment that just kind of captures this is why this is a fantastic thing to do I guess I will revert back to my roots as a physician and when something comes out of all of this that actually sheds a bright new light on a medical problem that was completely obscure before those get me pretty excited so when there is a kid whose strange disease was about to take their life and DNA sequencing turns out to explain it and not only explain it but explain it in a way that immediately suggests an effective action and that kid is now happy in third grade that that's like wow so can you tell us the story and I don't know if this is public or not but I'm sure there's a backstory for who was sitting in the box with the first lady and the so that was Bill Elder who's a medical student with cystic fibrosis and yeah that's that's another one of those moments of well you know how long has it been since the CF gene was identified 1989 I don't know does anybody know that in this one lap cheese lab and my lab banged away in that and it was so incredibly painful without a genome to guide you it would be so easy you know but now to have us go all the way through those many painful steps of trying to use that information and ultimately come up with an effective therapeutic and have it work so incredibly well for those people who have g551d in the mutation in CFTR and that's what Bill Elder has and here's this incredibly healthy looking medical student yeah who went from a pretty tough space that he was in now to in his view having a pretty normal projection of his ability to live a life that's pretty amazing and HapMap you know we started out this process of trying to discover variation in the genome is it going to actually turn out you can use this and where we early on in the process coming up and with the first what was it first 95 snips that people tried coming up with a very effective linkage for macular degeneration I mean it's like hey this is going to actually shed light who knew that that gene C4H was going to turn out to be relevant to this disease just those moments of revelation where you realize yeah we did all this work we built all this really cool foundational information and that was amazing in itself but it's starting to go somewhere it's starting to actually help people with really difficult medical problems that's the dream I would I mean the euphoric moments that I've had already in five years I would certainly say any of these examples where you see clinical home runs are euphoric for me especially as the person who I think has really worked hard to start to shift the institute's focus to include clinical applications of genomics and so seeing that relevance it validates it I have to tell you I have a lot of micro euphoric moments when I hear from members of the community when they say nice things to me and thank me because I have to admit following in the footsteps of Watson and Collins those are big big shoes to fill and at times you sort of sit there and say wow am I ever going to be as good as you know and it's at this institute has a lot of rich history and leading it as a little intimidating so when I hear from people in the outside world you know who come up and say nice things about what's happened to the institute my leadership of it I have to admit I find that extremely gratifying I'll tell you the third thing that because it in many ways it also represents a an expansion of genomics beyond a scientific discipline and that is it's relevance in society and I would say that one of the things I'm already incredibly proud of is the fact that we developed this partnership with the Smithsonian institution to create an exhibition on genomics which is at the National Museum of Natural History for 14 months and is now touring North America for five years and I'm proud of the exhibition but symbolically I'm proud of the fact that that it's been so incredibly embraced as an important thing to do because the relevance of genomics to society and that genomic literacy is now so important and to me not only do I think that's a great thing for the institute but as somebody who got involved in genomics on day one of the field as a as a young trainee seeing that maturation from you know this geeky scientific enterprise to sequence the genome to now making it relevant for medicine to now making it relevant for society I have to admit that that is going to be high on my list of proudest moments yeah Eric I gotta agree with you on that and along with that I guess another high point really was getting Gina the genetic information nondescript nation act passed that took 12 years of incredible effort on the part of lots of people with what appeared to be success always resulting in failure and then ultimately pushing it over the finish line and to be in the oval office when that was signed and then you knew it was really there that was a high point for sure and we had a great party afterwards and then all of these things that Francis and I just gave us highlights must be the reason why genomics gets talked about a lot in the oval office these days apparently and that that's got to say something too the fact that you know in just a little over a quarter centuries a very young discipline of genomics NHGRI has been the leader of it and here it is a major focus for the president of the United States in a real substantive and intellectual way that that says a lot about the field says a lot about the institute well thank you guys