 So we are, as I told you, we're gonna go a lot of order on the agenda in various times. So we're gonna have a presentation now by Karen Rothenburg. Let me just give background for those who don't remember. Karen is a member of the faculty at University of Maryland Law School, has been associated in various ways with our LC program for many years. And I asked Karen to come do a sabbatical for a year, starting last summer. NNHRI as a special advisor to me. In particular, there were a number of circumstances I thought I could use some one of her expertise to come in and help look at things, make some recommendations for me. Obviously we have the new strategic plan where we describe our interests in genomics and society as we've described it, which would certainly include the classic LC research program. But this also comes following lots of discussion about our LC research program over the years and lots of interest in seeing it continue to thrive in the future. And so Karen, as much as anything else, I've asked her to sort of look both historically but also to look in the future and to give me some recommendations as we go to implement our strategic plan in that area. And she's gonna give you an update on what she's been doing and her thinking along those lines. Thank you. I just wanted to first start by expressing probably something everybody in the council knows, but just the incredible goodwill of the people that work at NHGRI and how helpful they've been in allowing me the time of the interviews and looking at the data and helping with the assessments and getting what I need. I can be a little unrelenting sometimes. So I just wanted to express my appreciation. She's smiling back there, but particularly to Joy, who's just been wonderful, Joy and Jean and Elizabeth. And also to Chris, who if anything looks snazzy at all in terms of a picture, I thank Chris for that. So thank you. I also wanted to express my thanks to the ectromural grantees, particularly those that are in the Sears, but also all over the country, I've had a number of interviews, presentations, conversations, asked them to fill out questionnaires, and everybody without exception has been just wonderful. So I just wanted to start with that. You don't know for sure if you've gotten everybody, but if following this, anybody has any further comments to please pass on and I will integrate them as best as I can. So just for background, I know sitting around the table, I see different levels of age and maturity. So I went back to 1990, just to go a little bit in perspective, that the LC research program was established a little bit more than 20 years ago and this was the specific mission to anticipate and address the ethical, legal, and social implications of genetic and genomic research. It was unprecedented, and I want to emphasize it's unprecedented to have a specific set aside that started at 3% and then became by Senator Harkin within the year or two of the establishment of this program, 5% set aside of the ectromural research budget. And so what some would say was this was somewhat of a science policy experiment to actually embed and integrate thinking deeply about ethical, legal, and social implications of science. How this translates that in the last fiscal year, a little over the $19 million or almost $280 million over the last 21 years has been spent on this portfolio. And we are the envy of the world. There have been a few other countries that have been doing some research on what's been going on around the world and how they fund LC or genomics or society. Everybody has a different name, but we are the largest funder of quote, bioethics research in the world. I might also say we have established quite a legacy of thousands of publications that have now made it commonplace to do interdisciplinary work and have it published collaboratively. I wanted to just start by sort of setting a tone because I think we may take for granted that we have embedded an LC research program at NHGRI. But it does in fact pose some inherent challenges that I think we'll see some themes of as I go through this. First of all, just by definition, there's a clash of cultures, people that choose to be scientists and people that choose to go into law or to bioethics or maybe even some other forms of social science. There may be different clashes of cultures in how we define problems, how we communicate with one another, the kinds of research tools we use, and sometimes this creates some interdisciplinary mistrust. Sometimes I would say increasingly it has created more trust, but this becomes an evolution over time. It also is important that we clarify our goals and our roles because in different countries that have similar sorts of programs, they have different missions. So is our mission to objectively ask questions about anticipating what these implications are or as in some other countries where we actually are here to help work with society to promote enhancing genomics and genomics research. And depending what our goals or our roles are and they can be both, it may in fact have an impact on how we look and how we assess the program. The next two or three are sort of inherent in what it means to do this kinds of research. Again, it's not unique to this field but anticipating where the future is going to bring us, even looking at whole gene sequencing and trying to figure out where we're going with it scientifically is an interesting question. Certainly the bottlenecks that Eric always talks about are certainly very interesting, but it's also very hard to anticipate how it's going to make its way into society and how deeply it's going to make its way. And that gets me to this next point about researching, quote, society. We've learned from past experience that it's hard to know if hypotheticals, questioning the public in hypotheticals, what their preferences are, whether they're gonna go and get a test or not, in fact, play out when in fact that test becomes available. So how do you go about researching society? Who is the society? How diverse do you need the society to be and what kinds of tools can we really measure in the best way? And there's a lot of interesting debate in the field about this. Oh, I'm sorry. Next is this concept of genetic exceptionalism. So when the decision was made to put this set aside into studying the ethical, legal, and social implications of genetics and genomics research and what they might mean to us, what impact did that have and how in fact did it play out vis-a-vis all the other bioethical issues, for example, that just are not unique to genetics. We saw this conversation play itself out when the gena was passed and we specifically were focusing on genetic nondiscrimination and privacy. Is this a good thing? Is it a bad thing? It's neither. It may just be very contextual. Are there some areas where we really do need to drill down deeply because it's about genetics and genomics? And when do we and when don't we? And that becomes a very interesting challenge for us. And then finally, the final challenge, which is mine, as well as all of yours, and that is how do we measure the impact? How do we know in fact that this LC research has made a difference? All I can say is that it is a vibrant field and this point I'm gonna go through more and more of some of the assessment tools we used and we looked at, but in fact we have a thriving in this country, thriving development of genetics and genomics research. And I don't think it's coincidental that we also have a thriving LC research portfolio. So I wanted to just list for you, okay. Does something strike you just by this list? There's an awful lot of assessment going on about the LC research program. I mean, every few years there's another assessment going on about the LC research program and I think it might somewhat be tied to some of those inherent challenges. And in each of these assessments, there were in fact some common perceived tensions that continued to be described and I as a optimistic person don't actually see these as tensions, but I see these as opportunities and challenges that in fact it's not an either or, that in fact the LC research portfolio and its future can in fact reach a way to actually modulate what these tensions are. But I might also say they're not really unique to just this research portfolio. They raise in fact a lot of questions as you think about how best to create and promote a grants program. So the first is what I would call integration and objectivity. On the one hand, you wanna have an LC program that allows people to be objective in their work, including being critical of some of the trends they might be seeing as the science is moving along in the context of society. On the other hand, and that in fact I think had a lot to do with the beginnings of the LC research program. I think there was a lot of concern about our history of eugenics and a lot of concerns of what the implications were as we move to new genetics. On the other hand, one of the most exciting things that I see happening as the science has evolved and as there has been increasing trust in the interdisciplinary work is integration. I'm something that has really been fostered by the program directors in the LC research program together with the whole extramural staff here that as we have moved from organisms to humans, there has increasingly been the integration of from the very beginning bringing in the LC folks to say what are the issues we need to be asking and we need to be studying from step one. That is not something to take for granted and it is the envy of the other institutes on so many levels. So how do we do that? And still feel you could speak up when you're a researcher when something is of concern to you. Secondly, basic research and translation. Again, this is not unique to the LC research program but there is some value in science to just doing basic research and that's true here too. There are some basic normative questions that could be asked that are normative questions and they may ultimately impact on translation or they may not but when do we know and when can we just say to the philosophers or the lawyers, there just might be some basic research questions we wanna ask and we're gonna see how that plays out. The investigator initiated versus program initiated. Again, not unique to LC but NHGRI has had a tradition of having most of its extramural dollars be targeted and there is a very small investigator initiated budget in the extramural program except for LC. So and that's just by the nature of the science. You had a lot of scaling up and a lot of large and you still do. You have these large sequences, these centers for excellence. Well, the LC research program in the last 20, 21 years at its lowest level has been 50, 50. 50% investigator initiated, 50% RFAs and it goes up and down over the last 20 years. Right now it's just at about 50. What is the right percentage? Sometimes the investigator initiated has been as high as 70% but right now it's just about 50 and as you integrate more and more LC research into the scientific studies and those are RFAs you're going to see that percentage slightly shift. By breadth and depth, I mean diversity of disciplines, diversity of methodologies, diversity of people and what sort of balance we can approach there. It seems to me breadth and depth are both really important when you're dealing with LC issues. And then of course the consultative and research tension that all of you sitting around the room deal with on a daily basis. But this has also been a major, I think both excitement and frustration for the LC program because so much of what they're being asked as we move increasingly to having humans in our research is a consultative function. So what I wanted to take you through now is the evolving funding approaches over the last 20 years. So very, in very much in the beginning, in the beginning of the program, there were no RFAs initially. There was a program announcement, it was very broad. The focus and concern had a lot to do with privacy and discrimination. We weren't really dealing with humans at that point. We were dealing with, I don't know what you were dealing with, models and little organisms and stuff but not all that, yeah, worms and whatever. So, but soon after that, the other institutes, together with I think Francis's vision at the time, said, wow, NHGRI has money to look at the ethical, legal and social implications of genetics and we're seeing evolving genetic tests for cystic fibrosis and we're seeing evolving the beginning of some genetic tests for cancer. How are we going to study this? And how are we going to know what their implications are as we integrate these into clinical care? And the staff initiated, Elizabeth Thompson's legacy here was these consortiums in which I had the pleasure to be on that one involved with the Cancer Genetics Consortium to bring together people from different disciplines working on some of the psychosocial, normative and clinical integration challenges of starting to do certain tests, targeted tests for certain diseases. And what was really interesting about this and I wanna just share this insight. I don't think this was the first time but what it did was we were going to study this in research contexts. So we were studying this in academic institutions and we were in part helping to pay for some of the testing and this way people could get the results. And what we started to do in some of these contexts of research was we were giving people clinical results. Sometimes, sometimes not. Then we got into some questions about CLIA and what the implications were for CLIA. But what we did do is we said we're studying in the context of research but it has some implications for the clinic. And I think this is a model we still see here and it partly is contributing to this increasing blurring between what is research and what is clinic and what are our ethical obligations. And this was a very, very exciting time for the LC research program and in both in the context of cystic fibrosis and cancer. Okay, then we started to move along and recognize that at the same time there was a science going on we would want to look at some parallel LC issues and HMP and genetic variation were two examples of that. So you can kind of see the funding of the program and the needs for some RFAs was paralleling what we were seeing going on with the science. And the LC research program was getting the recognition from this from I think some of these were common fund HMP was a common fund to recognize, okay, where's the expertise? It's at NHGRI and bring them into some of the parallel LC RFAs. Then around 2004 kind of consistent with the model of NHGRI to have centers for excellence in science, genetic, genomic medicine, et cetera. And again, I think this was Elizabeth's legacy, Elizabeth Thompson with together I think with Joy at the end created this idea of LC centers for excellence. And we currently have six of these and two smaller P20s to bring together through a series of goals. I'm gonna defer, Joy's gonna talk more about this in the next concept clearance. But and these have been studied in some detail over the last six or seven months and I can come back to that because I see I'm gonna run out of time before I know it. Okay, then what we started to do is to integrate and Joy and Jean and Elizabeth were increasingly involved in these. And I know Terry could speak of the experience with the merge and we have now have also a new experience with clinical sequencing Eric mentioned with the return of results. But specifically in the clinical sequencing which is our new proposal, you could not get scored to get a grant unless you also scored high on one of the strong components which was LC. Now, think about whether or not we could have had that happen at the beginning of the LC research program. To have people, scientists, clinicians and LC folks collaborating and working together to put together a very significant grant in which they trusted each other enough and they did it well enough in all three components to get scored. And there were, I don't know if we could say how many but I brought it would be say many of these applications. Interestingly enough, also many of them have a co-PI who's up quote LC type but a lot of the people that have become proficient in LC issues are actually geneticists. And so that has also been very interesting that they have learned either through their work or through additional support from others in the field to really integrate and understand these issues in the context of their work. And then finally, as Eric mentioned, the integrated consortium model for return of results. So what this shows is as the science has matured and the field of LC has matured, the different approaches to funding it has also adjusted to what is needed in order to get an integrated approach when appropriate. Again, thinking about what's going to happen with objectivity, I do have some concerns that do we often ask the normative foundational questions before we move ahead to ask some of the implementation questions. So just a thought, this should be familiar to all of you. I just wanted to show you the breadth of the range of mechanisms that we use in the LC research program. The only one that is not now currently being used is the educational grants, and that is in direct response to an assessment that was done in around 2003, 2004, saying that that was just not a good use of the limited resources to do the research in the field. Okay, this all looks familiar to you. I would hope by now. And so does that picture up on the top as we quote, move to the right? That's kind of an interesting thing to say as we're debating in the Republican debates, et cetera, but in any way, moving to the right. There was clear recognition in this strategic plan of a commitment to this domain of genomics and society, and all the way on the left, all the way to the right, what in fact are the implications? I think it's interesting that it has an and sign, so it means genomics and society. Eric said that stands for gas, and maybe we have to think about that as an acronym, right, G-A-S. But I think what it says is it works both ways. So it's not genomics in society alone, but what societal impact is on genomics and vice versa. So I'm gonna have to go quickly through these. These are coming out of the strategic plan. These are the four categories, but they're also pretty much the categories that we've really had from the beginning. And you'll see how this plays out a little bit later. Increasingly, as you move to the right, the impact of one and two and the impact of three and four, they're all interrelated to one another, but they've been put into these four categories. This is the listing of what would fit within the category of psychosocial ethical issues in genomics research. As you can see, there's really nothing unique to genetics and genomics. These are issues that are raised by all types of research, except perhaps the intergenerational and the blood-relative relationships that may create some interesting challenges when it comes to, if you get consent from somebody, what impact might that have beyond themselves to their whole family. But, and there seems to be some perceptions that genetic or genomic research might be more sensitive to individuals and their families. That's this interesting question about exceptionalism and where that plays out. Let me just stop, but on community engagement, I was going to say, this is an area where we have gotten some wonderful scholarship coming out of the Emerge Consortium that specifically had a focus on consent and community engagement. It's also an area where we could learn a lot more from what's going on around the world. I think particularly there's some fascinating work on community engagement in New Zealand and Australia, as well as in the Netherlands and in the UK. The psychosocial and ethical issues in genomics medicine, I don't think anything should seem unfamiliar here. I just think this first one of genomic uncertainty is a real challenge for us. And what do you say when we don't really know and how much is good enough when you're going to give a result? And when does a result, when do you think that it's really time to share information and we're like a moving target? And I think a lot of really good research needs to be done in that area. On the legal and policy issues and the next one on society, you'll see some overlap. Again, I don't see anything really new in this. This is all listed in the strategic plan. I think increasingly this non-medical setting may become increasingly more important as we more and more integrate into society, genetic and genomic information. And then this last broader societal issues, these tend to be most of the grants that generally don't cost as much. These are grants that are usually given to philosophers. Many of these same issues that were discussed in the early 1990s are still being researched today. What does it mean? What is it going to do to our sense of self? I think the individual and group identity issue is becoming increasingly more interesting and more important. And free will and individual responsibility is something that we lawyers love to talk about all the time. Okay, now the next two slides, I want to give a little caveat. And I give credit if you love these, if you love these to joy and if there's a problem, I will take responsibility. But joy and I think we ought to have Jean look at these as well. And Elizabeth, we tried to squeeze in from 1991 to 2011 into these four categories as best we could. How much money was spent in each of these four categories to just give you some sense of some trends. But I want to give the caveat again that there's a lot of inter bleeding between categories. And if you look along the bottom, that will give you some perspective on how much was spent in each of these five years. And as you could see from 2001 till now, that's just a function of the extramural budget not going up much. There hasn't been that much of an increase, but in that first 10 year period there was. So some of the obvious things seemed to me the trend of the amount of money spent in the legal and the social by percentage was much higher in 1991 than it was in 2011 when we were first just getting started. And if you look together in 2011, the genomic research and the genomic medicine categories. Now remember, that's the LC issues associated with genomics research and genomics medicine. They're accounting for about 70 percent, a little more than two thirds of the budget now. So they're together, that's the large majority of what the portfolio is looking right now. Now, do you think, well, why would that be? Well, one, what's happening with the science, you might say, why was 1996 so high for genetic medicine? And that was the cancer genetics consortium ending, there was a large proportion of the funds going to funding clinical integration. And there still is a large amount of money going to clinical integration. And there's a large amount of money going to behavioral and social science research. And a lot of these are integrated RFAs that are accounting for this. And I don't know what else to say about this, but I'm happy to answer any questions. But what it does show, I think, is sort of the maturation of the program, but a little bit of concern about whether we're doing enough on the legal and the social issues. Maybe that isn't a concern. Now I wanna compare it to, this is the number of grants. So if you look at the number of grants, it's mostly parallels the other chart, but you see a larger percentage by number of legal and social. And like I said, that's because those are inexpensive grants. Those also tend to be investigator initiated, but not totally. The return of results proposal just had, in fact, some opportunities for some of those more normative studies. But that gives you a sense of the trends as well. If you look at the bottom, as you can see, we just have less grants. Even though we have more money, we have less grants than the high, in fact, of 2001. And that's because these integrated social and behavioral science with a lot of empirical work are just more expensive grants. So we can't spread quite as much as we would have if there were just a lot of little small grants. Well, that's obvious, I think. So that's how it's played out. Now, then I did these in 1991 with Chris's Health, these clouds. Now, it's interesting, in 1991, there's a lot of human out there. Look how big ethical is, too. But human, because everybody's grant had the title, Human Genome Research, Mapping the Human Genome Implication, Ethical Implication, so that's where you see human. But this is more interesting to me. So this was 2011, and look how big research is there. So the ethical is like a little thing over there, and I think legal is even a little more. But research that so much of the ethical, legal, and social implications programs focuses, what is the implications of genomics research? And I don't know what to make of that, but I think that says something. And that says a lot about the integration of the program. Are the grants themselves, research grants? Yeah, but that wouldn't be in the title. Oh, I see. Yeah, yes, yes, yes, they're all research, yes. Okay, so then we did another analysis. But based on our data sets, we could only go back a certain number of years. And this is by the number of awards, by methods. And this was because I had some concerns that we didn't have enough diversity in the kinds of methods that were being used to do research. So there were 141 awards over this period of time. And you could see on the left-hand side by multiple methods, that actually speaks to, again, interdisciplinary work. It means people from different disciplines or skilled with different methods have gotten together to be able to address some of the focus on some of these RFAs that really requires that to be successful. You have multiple methods. If you look along the right, the legal only, and the conceptual only, those tend to be those in that third and fourth category. And the other just tend to be databases and things like that. And then I also wanted to see, because one of the critiques from the ELSI research program is, it doesn't really do, I wanna say this in a positive way. Could it be doing more to actually have an impact on policy? And in, again, a review with some of the people in the policy shop helped the assessment. Alice Bailey and Laura helped with this as well. In looking at them, regardless of what category we placed them in, we did a search based on their aims and whether or not they had the goal of coming up with some sort of regulatory or policy development. And as you can see, almost half of all the grants funded over this time period did. And I think that's an underestimation because as you move in your research, you're going to increasingly impact policy eventually. But as part of the specific aims on these, they specifically mentioned that. Okay, so now with my five minutes I have left, what I wanted to do is to broaden our scope past the extramural program. And this in part is because of the other hat I wear. So half of my time is spent in the bioethics program at the clinical center working with the bioethics core, which is mostly Sarah Hull and Ben Berkman who are incredibly talented and work with NHGRI and the intramural program and write about issues in the field. And the second, the third, the intramural branches, that's the social and behavioral research branch that when Eric was scientific director, he established to do work, this is Colleen McBride's branch and actually Vence is back there as one of the members of that as well. And he does very interesting work in the intramural program, a lot of very interesting work on the role of race and interests of physicians and healthcare providers. And then there are other extramural research branches that are primarily medical or clinical but also care and are involved with LC issues, Lesbysiker's branch for example is an example. And of course, the Office of Policy Communications and Education and the ability to do better, even better among all these components so that the LC research program's portfolio can inform what's going on with the evolution of policy. And the policy shop can tell us what's emerging as new issues that in fact we could be doing more research on. And we could learn from the intramural program who's doing a lot of work in return of results and a variety of the ethical issues associated with that with IRBs, what we could learn from there so that there would be better integration and more of a critical mass even at NHGRI alone, not to mention the rest of NIH. So what this represents, not to study in any detail now but over the last few months we have been bringing together the intramural folks, the policy folks and the extramural folks on the ground to talk with each other about what in fact it means to do genomics and society research. And on the left hand side we listed all the potential disciplines that we could be engaging with to talk about and to enrich our research. And on the right hand side all the potential methods that we could be using to do research. And then along the bottom, and remember this is a draft, along the bottom, sort of a continuum that probably shouldn't be next to each other but in some sort of schema that I couldn't develop at this point on the chart. But if you look along to the right, moving from basic knowledge to tools and methods to validated interventions to research guidances to practice guidances to the making of public policy and how they would interact with one another. Now, more important than what is said on this chart is the fact that everybody with goodwill is working together to try to think outside the box to how we could further enrich our genomics and society research not only at NHGRI but beyond. And that's where I really wanted to leave you. So the first question is at NHGRI, how could we do better integrating extramural policy and intramural to enrich not only what we talk about here but also beyond NHGRI and beyond genomics with other NIH institutes. There is not an LC research program in any other NIH institute. But the large proportion of the budget to do genomics research is not at NHGRI. I mean, it's in other institutes and they have these same issues that they're dealing with and they need us and we need to work together. And I think coming from that will probably be, I would hope, more involvement with more institutes contributing to collaborations. We've started to do it, but we could even be doing more of it. And then beyond NIH, there are a lot of other federal agencies and organizations. I look back in 1990 and 1991, we had an agreement with the National Endowment for the Humanities to work together on one of our grants. We could be doing much more of that. And then of course we know we have to be in the LC research portfolio just like H3Africa, we have to be much more expansive in where, just like in the science, where we have so many international consortiums to share samples and to share our ideas, we need to be much more expansive in this area as well. We can really learn a lot and we can collaborate so our sense of what society means can be a lot richer. So I think I'm done and I realize I didn't leave much time for questions. Could I have a few minutes maybe for questions? I just was a little bit confused when you were showing the funding side about how ethical and legal and ethical or legal and societal went down. Oh, sorry, went down. This one, the grants or the money? Well, either one, the money, I guess. I just wasn't quite sure what that meant. Aren't the legal and societal things included in genomic medicine and genomic research? So did you lose out by not having that? That's what I wasn't saying. That's a really good point. When I said the caveat about how they get, so we had to put them in there the primary place. So in an ideal grant for the first or second category, it would be wonderful to have people that have those skills to be integrated into that grant and they would have been put primarily in the first or second category. And I think your point is, is it possible that it's just underestimating how much of a value is in those other grants? It might be, but we may need to be, there's a perception that we're not spreading the wealth enough to enough disciplines and enough areas and we have to be mindful of that but it's a very good point. So let's start about spreading the wealth and whether the coverage of the topics are not being done. Is it your perception that we need to do more of that? Well, I hate to generalize, but I do think, and there's some people that have probably heard me say that sometimes I think we may jump the gun a little bit and that if I could go back a few years, I'd say, wow, I wish we would have funded maybe some more normative analysis of the foundations beyond why we have some sort of evolving obligation to return research results. And I think now we're talking about the social and behavioral implications of returning the results. And I think maybe if I would like to see a little bit more depth of scholarship that had just been on some of those core issues. So that might have been an example of that. Yeah, Amy. On that line, I mean, have you done or do any sort of needs assessment both within the LC community and within the scientific community of what are the perceived needs now in terms of where the funding should be going? That, I think that's a great question. I've only done it informally and through the SEER structure and of course those are successful grantees. I think what we haven't had for the last few years and Eric and I have talked a little bit about that there's not an advisory group. There isn't an advisory committee to LC. And I think as we evolve and move forward, that would be very helpful either as a subgroup here where we would bring some other people to the community and talk about that and then figure that out. But I think that's a really, really good point. And yes, that needs to be done. Yeah, I wanna thank you for your overview. It's really very helpful in given a sense of the evolution of the LC program. What I didn't get from you and I'm not sure how easy that is to do. I have two sets of questions, but from a research perspective, what would you say have been some of the signal successes of the LC program and are there really missed opportunities in terms from the research science perspective? You talked about missed opportunities in terms of policy and get in some of the research into policy, but are there some other big missed opportunities we should be aware of as we think for the future? And then I have, let me answer that one. And then I have a second question. Okay. I think it's always interesting to be a Monday morning quarterback. So let me talk just first about where I think some of the major positives were. First of all, I do think the whole conversation about de-identification, tissue samples, what you need to have consent for, the richness of that conversation was starting in the 1990s, mid-90s, but I think a lot of that got moved along rapidly by some of the initial work that was done coming out of the LC research program in the early, around 1994, I think was sort of, and we're still talking about it and we see it now coming up as we change the common rule. So I think that whole area got a shot in the arm from the LC research. And now the other area I was thinking about is genetic non-discrimination and privacy and the ultimate passage. I don't know how much of that really came from having a research program as much as what it means symbolically to the community as well outside. So there is a study that came out that showed that just about 20% of LC research is funded by NHGRI, most of it isn't funded at all. But so the stimulus of the recognition may have stimulated that. So that could say, well, for the amount of seed money that we gave to the world, now, what do I say, 280 million dollars, we've established this much larger portfolio. Now, would that have happened even if there hadn't been any of this? Who knows, I don't know. As somebody that was in the field then, I mostly unsuccessfully applying for grants. I then wouldn't get it and did it anyway. So in my field or in philosophy or in law and those kind of fields, the investment isn't quite as deep as it would be for somebody that has to do a lot of empirical work. I think probably the greatest success is what I said about this recent clinical sequencing grant, that we have created a generation now that both ways of social scientists and other people that are not seen primarily as medical or healthcare professionals who know how to interact collaboratively with the scientific community and vice versa. That there is sort of this evolution that took maybe the LC research program to do. And again, I don't have empirical data to back this up, but we have a robust and moving forward scientific agenda that I think has been enhanced by the fact that there has been a recognition and a seriousness of the fact that it's messy and that it's not all so simple that we're just gonna move forward and we can't do certain things we might wanna do if we don't get consent from people to do them. Maybe we would want to, but so that dialogue, it's messy, but it has enriched, I think, the recognition on both sides. So that's not a specific study, but it's almost just sort of a message. Does that help? Yes, that helps. My second question, which may be less for you, maybe even for Eric, but as I listened to your overview of the LC program and got a clear sense of what it is and what it's goes on, what it's mission, it seemed to me that a really critical issue that is noted by some geneticists and certainly by many social and behavioral scientists for the future is really to better understand as we understand genetics, how genetics interacts with environment and that we really haven't taken very seriously the social environment and really began to create the social genome, if you wanna call it that, and characterize specific exposures, especially psychosocial exposures in the environment and understand how they interact with genetics and how we can get epigenetic effects from exposure to distinctive social exposures. As you outlined what the LC program does, I thought in my mind that the LC program saw itself as possibly being a leader at least, not necessarily having the resources, but the thinking, this is very difficult to do, I mean, from multiple perspectives, but I think it's a real priority for the future and it didn't seem to be part of the mandate of the LC program as you described it and then if it's not the LC program, where within NHGRI would take on this major responsibility? Yeah, it's a great question and then, okay. The question I was gonna ask, which I think could lead to an answer here is when did you have the opportunity to actually talk with other institutes about how to integrate the work that we do with them because a lot of the epigenetics isn't here, it's elsewhere and I think that's one of the most important future-looking things that LC can start to do is to really build programs with other institutes. Okay, first of all, it's a great question. So first to be fair, because I didn't have enough time, the SIR program actually has a P20, one of the smaller centers that is actually focused on epigenetics and that's in Oregon. That is the PI and that is Nancy Press and the SIR at the University of Washington, which is the PI is Wiley Burke, they actually have done increasingly more and more of looking at that very question, David, you might know about that. And it is a priority area for the LC research program and it could be doing more of that. Now I think the PAM's point that I wanted to build on really goes beyond the LC research program and that's the and beyond part of what it would mean for the institute to really be the leader at NIH on genomics and society and that really goes beyond the extramural program. And that would mean that we would be seeing on the NIH campus just like the LC program has seen but beyond that of being able to bring together the critical mass regardless of where they sit. They could be in the policy shops, they can be in the intramural programs, they can be in the extramural programs, they could be in the Fogarty, I mean they could be anywhere and there would be a critical mass that would be working together to be engaging and talking about where we need to go with these things in the future and as you said, different institutes bring different expertise. But we already 20 years ahead in some ways but we need, that's where I see the and beyond. So the great questions. There are a couple more. Jeff's not gonna be talking to me. Okay. I have a million questions but the one I'll ask is, did you spend any time looking at what I'm gonna call a communication or implementation gap in that from where I sit, I'm aware of the LC research but on the real life side, I'm having to respond to regulations guidance in order to get the money from the same institution that funds LC research which oftentimes you go, this is completely off base or the advanced notice of proposed rulemaking, the president's commission filing the Guatemalan disaster. I feel like LC research is going on but it never cross pollinates. And it kind of follows the same discussion that I think both Howard and Richard had regarding at the end code, people don't know what NHGRI is. So I don't feel like you've adequately come out even within the primer of the ethics group. So I just wanted to feel for that. Yeah, I think it's a really good point and it's true. So I'll just ask a question if I might. How many of you know if you go on the NHGRI website that every single LC research grant that has ever been funded is on there? Amy, because she's a grantee. Okay, all right, and Michael. Okay, I didn't know that. And I had looked at money in the past. Okay, every single grant from the beginning by name and by search term. So first of all, that's an incredible resource, it seems to me, that we're not utilizing even with NHGRI. So the intramural people that are doing research in an area can go onto that website. The policy people that are trying to write something on some issue, besides looking at the publications, which are only part of the story, they could find so much more. The sort of the education, I don't really use the term marketing, but in fact, there is a president's commission, nevermind Guatemala, I mean, they're now looking at whole gene sequencing from genes to genomes. We need to do better at being able to share with them everything that we have funded and the policies that we have, and this very much needs to be more of a priority. And in fact, I think if we do a better job at integrating by definition, it will be done better. Follow up on that. I mean, it seems to me, Pearl, that that sort of gap comes in in those almost 50% or just over 50% where grants that claim to have a policy impact or do some sort of policy research, right? And so it might be interesting to look at what are the methods that are being used in those projects and are they effective or not in actually making that sort of crossover? Because that's I think where you get the cross-pollination is in the projects that are set up to have some sort of policy implication or regulatory implication and are they doing that or not? Well, one, we could have a deeper synthesis of what's come out of those. Written or not written. I mean, publications are not publications. But and in fact, one of the centers for excellence down at Duke now is doing a program with their students, doing a similar sort of project right now, looking at the sort of the policy evolution in the development. So I think it's a good point, very good point. Yeah. So during the introduction, Eric mentioned some NHGRI initiatives that parts of it spun out to other places, NCADs, other places. It is, what's your take on whether ELSI should be spun out to NCADs or some other entity that allows cross-pollination to more effectively occur? Because in some ways it's NHGRI's 20-year experience and other people think, well, NHGRI will just do it. So I guess it's a philosophical decision, I guess, about what's the best strategy. There has been increasingly, although when money is tight, people are tight with their money, the NCI, NICHD, and a few other institutes have joined together to do some joint ELSI projects with NHGRI where we've taken the lead and it works other ways too. The SEAR program has as one of its three major priorities training and some of the individuals that have been trained through the SEAR program are now here at NICH, but not at NHGRI. So I think those will be ways for us to better cross-fertilize. I think the decision about whether the ELSI research program and genomics in society should be somewhere else is not something I would be in favor of because I think it's unique and it's something that this institute should be incredibly proud of and that just like the precursor to NCATs, that was germinated at NHGRI. I mean, a large part of it, as I understand, Eric Kirkman from Rome, was germinated here and I think just like we were the leader to map the human genome, the paradox in some ways, as I think Jean pointed this out to me, is that this was the institute that made this commitment even when we weren't dealing with human beings and we have created the expertise to lead and I think we should be leading. I don't think we should be receding. So that's from my perspective, but I think it's something we should be proud of and we should figure out how to better integrate it within NIH, but not leave it behind. Okay, on that note, I think we'll leave this as clearly going to be subject to future discussion as we sort of think about the future of our Genomic Society program. But Karen, thank you very much. We're going to,