 Okay, next on the agenda is a presentation from Larry Brody. Larry, do you want to share your screen and bring your slides up. Larry's presentation is in response to a request from council that came up at council initiated discussion, I think maybe back in February. And that was that the council said it would be informative and useful to talk about what kind of research activities related to the LC research program of NHGRI are going on across the NIH. So we tasked Larry with this responsibility to bring us this presentation. And are you ready, Larry? Yes, can you see my slides? I sure can. So can everybody else off to you then. Okay, thanks Rudy. Good afternoon everyone. I've probably heard this one of the first rules to show business never follow an act that features animals or children. So we're going to break that rule and follow an act that had a lot of animals going on. So you asked about information on LC and LC like activities. You'll see what I mean by that in a second across the NIH. So what I'm going to do is take you through mostly a very, very high level view of various activities going on at the NIH, and I'm going to do a little bit of a brief overview of the process of stopping to go to a lower altitude for some specific programs and some that are just examples of other things that are going on. And then address a little bit of how you can dig in and get into more details. So, but before I do that, I want to do a quick overview of our program just to set the scene a little bit about collaborations that we do with other ICs. And then show you a little exercise in data mining to try to answer the questions about what's going on in LC like research across the NIH in a much more agnostic way than some of the earlier work. If you were to ask this question of the NIH reporter, which I'm sure many of you are familiar with, it's a readily used public database. And you just simply searched the word biostics for active funding in 2020. You would find that 266 awards use that term. If you restrict that search to research grants, which is a function of the reporter interface, you'll find that there are 82 that use that term. And then you'll also find that 21 of those are actually our grants and HGRI support grants. That's really a very, very simplistic way of doing it. And you'll see that it's much more complicated. There's a lot of gray area when it comes to answering this question, what kind of LC work is going on at the NIH? One thing that I think I use this to illustrate is that the NIH, when you look across all the institutes, the center of gravity is clearly in things that they term bioethics. And hanging off of that are a little bit of legal research, again, mostly in our institute. Social science research related to bioethics, but lots of social science research that is not necessarily in the bioethics or the LC realm, as well as a very, a lot of larger programs in behavioral science. And I take the view that some behavioral science overlaps with LC research, but there's a lot of behavioral science research that's quite important, but not considered LC research. And I'll show you where some of these programs lie. Just keeping in mind that some overlap to a little bit with LC and some not as much. At NHGRI, we have programs into ethical, legal, and social implications of genomics and genetics research. And those are not necessarily disciplines in themselves and that the social science often use social implications, but you could have economics to look at social implications and ethics overlaps with legal and so forth. So this is our universe of research areas, but they're all surrounded in the genetics and genomics box. So what we would like to do is evaluate what is else is going on in genetics and genomics in the LC sphere across the campus. And I will get to different approaches to doing that, but I want to talk a little bit more about some of the programs that we do. I also want to just remind you that LC is one of the three divisions or one of the disciplines within the Institute. But there is a significant overlap now probably more than ever, maybe not 20 years ago, but now between genomic science and genomic medicine. And it's easy to think of areas where these two interface. So not all funding and not all grants are cleanly in the LC bucket. Some are overlapping between the two. For a very long time. A lot of LC work was focused on intellectual property, which is an overlapping with genomic science. And you can see these other topics that overlap with genomic science, as well as topics that overlap with genomic medicine. And I purposely put equity and data privacy in both overlaps because they do overlap in both directions. So what's the scope of the LC program? You heard from Carolyn this morning that the LC program is a set aside. It's funded by approximately $22 million in the most recent fiscal year. We have approximately 65 grants funded by the LC program and actively managed by the LC program. That's in comparison to about 500 for all of NHGRI and about 50,000 for all of NIH. And so just want to keep in mind those kind of almost order of magnitude jumps as you go from the LC program to NHGRI and then to the NIH as a whole. And we're going to mine data from all of those pools. Almost all of our grants come in through our program announcements. And those are on the web. And I should also mention that for those that are interested, this talk like the others will be posted. And all of the web resources that I am going to list will be down in the notes section of the posted talk when it is. So there's, you can recreate most of what I'm going to talk about by going back to these resources. So it's just to illustrate our program announcement. How do we connect with the rest of the NIH? Well, I'll tell you historically, it was centered around program directors. And so there is a quite a long history. In fact, we have program directors that have been with the Institute for more than 20 years now in the LC program, namely Joy Boyer. And so there's, that's time to build a lot of personal connections to each other, to other program directors at the NIH. We've also done tea times where we've invited back when we had a time, had the space to do this, we invited other program directors over to our place, either virtually or physically. For our tea and cookies to talk about LC work that we were doing and how we could collaborate. The NIH puts out now these things called noses, which are noticed of special interest. This is when a institute is going to do research and propose research or funding or announcements in a particular area. It's placed in a repository where all the other institutes can look at it and decide if they're interested in cooperating. And then the last way we actually build connections outward to the other institutes is what I call pedigree. And we have folks that used to work at NHGRI that now work in other institutes. And that essentially creates an existing network of LC contacts in other institutes. Through our program announcements, which we have one for different mechanisms, we have through these connections that I described on the last slide, we have several institutes that have signed on to our program announcements. And that means that they can take grants that come in under this program announcement and fund them as if they were their own. It also means that they give us, they have the capacity to add special language to our program announcement as to what they're interested in. And I'm showing you the one for the R01 mechanism, and all of these institutes have signed on to essentially accept grants that come in through this program announcement. We have another one of these for different mechanisms in the Fowardy International Center, which I'll mention in a second has also signed on to a couple of the other announcements. And so this allows us to both co-fund as well as have them accept grants that fall into their area. I've used this term that we use internally. It's not a formal term. What about other LC like or LC OID, which is an awful term programs at the NIH. And I'll give you a quick survey through those in a second. Just note that they vary in intent scope and stability. There is a 20 year trend toward more of these programs that can help address LC research and LC problems. They do cover a large range of questions. And the research that's supported in the other ICs or a mixture of standalone programs where you can get a grant, specifically for an LC topic to ones that are embedded and grants that are then supplemented with or to carry out LC research. So I'm going to go back to the supplement route in a second. So I'm going to just do a kind of a walk through some of the bigger programs. One of the largest is run by the office of behavioral and social sciences research. I would just preface this in our view. This is not an LC program. It's behavioral science program. And you can see this if you look at their priorities. Although there is some overlap with some of the funding that they have given and LC programs. And we have done cooperative programs with them, but their overall mission is not an LC like mission. There is also the Fogarty international program, which supports research in other countries. And as you can see, they actually have a very specific bioethics page where they can fund both the creation of resources and research grants. And we cooperate with the Fogarty international center and every year, co-fund some of their grants that come in. So there is LC work going on internationally through the Fogarty international center. Completely transparently as you have. There is also when you may not think of resources at the NIH, there's also a very large department of bioethics that is mainly focused on the intramural program, although it does have a lot of research. It's basic research as well. That program provides an ethics consult service like many of you have at your institutions. And we have used, the LC program has used that consult service on occasion. And features 14 faculty and each, there's 14 trainees that go along with it. So as a bioethics department, it's a relatively large one, I think, compared to what some of you might have at your institutions, and it's headed by Christine Brady. And I have the faculty, I'm not showing you the whole list, but I just want to highlight that two of the faculty in the bioethics department hold appointments in our institute as well. And that's Ben Berkman and Sarah Hall and most of their work and most of their research focuses on genetics and genomics. The rest of the faculty do occasionally get involved in genetics and genomics, but it's not really their main tactic. Just highlight one example from another institute. So several institutes NHLBI, NCI, NICHD have some dedicated staff to LC programs. Just highlighting the NCI program because you'll note that the program director in charge of this is a JD. That brings legal expertise, which is somewhat uncommon at the NIH. But I also note this is, if you have cancer questions related to cancer that might be LC questions, Charlize Kagaanan is the contact for bioethics and they actually use the term LC right in their website. So that's one of the few programs that actually spells out LC research. And we have worked with the NCI and the NCI has a fair number of programs dedicated to LC research, but of course they have a focus on cancer. One of the largest additional sources of resources for LC research at the NIH that is not in HDRI is this bioethics trans, trans NIH bioethics funding awards. It's relatively cumbersome term. It's based out of the office of science policy, which is part of the office of the director, so Francis's office. And this fund was created, I think about a decade or go, and to support bioethics research at the NIH in a trans institute way. The last couple of years it's become much, much more active and they have $5 million worth of funding each year. And they mostly use that money to fund grants that other ICs bring to them. The ICs nominate grants. The office of the bioethics group vets those grants and selects some for funding. And then the money is administered by the ICs. Not all of the $5 million is given out every year. There are some office director uses for that money. But as a single dedicated part of funds for bioethics research, this is the second largest at the NIH as far as I know of it compared to ours, which is the remains the largest. Most of what they fund are supplements to grants. I said I would return to supplements quite often. A supplement is when the institute has funded a program and as it gets rolling, someone highlights that there are some ethical, legal or social issues that need to be addressed by this program. And that's when they ask for funding and they can use that to add on programs that didn't originally have an LCA. I just want to show you just a few examples that were funded recently. Here's one from the drug institute. You can run through each of these, but you can see that theirs was on opiate use, national institutes and nursing research about funding for end-of-life care and bioethics there, allergy infectious disease, had the support of some international efforts that we're doing. The dental and craniofacial institute just funded two grants related to facial dysmorphology, including one that features genomics. Note that the previous examples did not include genomics. Here's one that actually does. And there's about a dozen or more of these that are given out each year. They are one-year funding increments, although occasionally they do fund grants for multiple years. That's the broad landscape at the NIH. And I'd like to zoom in now using and asking, what's the landscape for genomics and genetics? As you saw, I touched on a little bit that happens in other institutes, but the majority of what I've talked about is not genetics and genomics. And this also includes one that I didn't mention that's well-known is the brain initiative has a relatively robust neuroethics component, very little in the way of genetics and genomics in that program. So what we did to answer this question was we went to the RCDC program, Research, Condition and Disease Categorization Program, which is a collection of individuals at the NIH who are making the fact that the NIH funds 50,000 applications a year, and we get the full text of those abstracts as a great resource for data mining. And so what Renee Sterling did is she went into the grants database to do some text mining and data visualization. The staff of the RCDC program is actually extremely helpful, and in fact they are now establishing new taxonomy for genetics, which they don't have right now, we're just using free text. And so when we went and looked at the data from 2008 to 2020, so we first asked with a bunch of terms and related terms, are these grants that are related to ethics, genetics or not? And quite a few were not. Then we asked, are they LC research? And the answer was quite a few of them were not. And this is because bioethics, ethics and a lot of the keywords get used for training, especially for programs that train graduate students and ethical use of data. And it also included places where the investigators said that they had bioethics experience, but the grant itself wasn't a bioethics grant. We take the 53 grants that are clearly genetic and clearly LC research and ask, what are they looking at? This is a visualization tool, first saying what institutes have they come from? And so it's taken me a while, I still don't know all of the two letter codes, but this is Child Health and Development, this is Cancer Institute, this is my Darity Health. So the bulk of grants that are funded in the genetics and LC area outside of our institutes and none of this is our funding. In fact, we've excluded cases where we are cooperating with them and the program directors from HGRI are involved. So this is all outside of our portfolio. These are the institutes that are the major players. You'll note that minority health is a relatively small institute, nursing institute and our relatively small institute shows up in this type of analysis. And other large institutes like infectious disease, heart, lung and blood and diabetes and digestive disorders show up as much smaller players despite that they are much larger institutes. You look at the projects awarded by mechanism that's shown on this slide. Sorry, I'm just going to move you so I can see. Most of them are R01 projects. Again, this is 53 projects in the last decade, but there are other mechanisms used. I believe we excluded T awards from this. Very few of the other institutes have training grants that focus on LC research. So you can see the usual distribution of large awards down to other different mechanisms. And then if you ask, using again the text mining tools, what are the keywords that show up in a statistically significant fashion in these applications? Some of the most robust ones are genetic research bioethics. I think you can see the fainter ones are the subcategories. Informed consent making a relatively large appearance as well as ethical issues and genetic research precision medicine. You may wonder why Africa and Washington show up. That's because these text mining tools are looking at all the text and it's not field delimited to certain fields. And I believe it's WashU has several grants in a large number of centers. So Washington rises to the statistical significance and there are several grants related to Africa. So that's why regions show up as well as conditions. All of them are, the algorithm is relatively agnostic about what something is just looking for . So that's one of the key words. Genetic counseling from the other institutes is surprisingly and maybe refreshingly a priority or at least it has been funding wise. So these topics do mimic and mirror a lot of what the LC program does at NHGRI but there's some that are quite, some keywords quite specific. So I think that's one of the things that's really important. And I think that's one of the things that gets nicely in the domain of NIDGK and other institutes have their specific topics. If you then ask how much money is being spent and I will give you a caveat that this is imperfect numbers but they're probably not wrong by an order of magnitude or even wrong by two . So the LC research that we would consider genomics and genetics in other institutes, not ours, has crept up to about $8-9 million a year. And that's a reasonable sum if you think that it's a little bit less than half of what NHGRI dedicates. It sounds okay but keep in mind the rest of the NIH is $40 and it's a small amount from the rest of the institutes. If you want to see what this looks like from the point of view of a table, this is the total cost and this is now project years so in 2010 there were 11 full-time projects and so on. The dollar amount being spent has crept up and the number of projects has also gone up. Here's the bottom line is that NHGRI still funds the majority of genomics related LC at the NIH probably not a surprise to you. Some ICs actually have stable programs including the office of the director program not always targeted towards genomics and genetics but they are stable. That allows us to create collaborations and colleagues that are quite a bit of LC research and other ICs what I called it follows projects as I mentioned they have a project and either when they're starting to fund the research or hopefully before they fund the research they realize they need to embed or have an LC related aim related to the research and I do believe strongly that NHGRI still in this area remains the exemplar highly cooperative and highly collaborative and a cheerleader for the campus when it comes to LC research. With that I just want to thank the team, the LC team at NHGRI shown here some of them you've already seen and just give a shout out to Renee who dealt with the RCDC classification and weighted in and gathered all the data. With that I'd be happy to take questions. Questions for Larry. Oh Jeff go ahead. You're on mute Jeff. Still on mute Jeff. I apologize I lost my screen there so thanks Larry that was really terrific and very thorough so encouraging certainly for the most part to see the trends in the right direction although I would say that the genome institutes program has been around for a long time that might have wanted to see sort of more concrete progress in terms of the genome model and that's the sort of 5% set aside that is unique so I guess I'd be interested in your speculation and welcome any comments certainly from Eric too about you know what other institutes think about that 5% set aside model and whether that's something that's ever going to be realistic for other institutes and centers at the NIH I mean I'll give you the personal answer is that it probably won't fly at a 5% amount in the other institutes I think that having some dedicated both program staff as well as funding stream I think would be really useful in the other institutes calling out a number I think would be really tough and may not be appropriate for all institutes I do think that if you look at the research that goes on in all the other institutes it's pretty easy to find an LC question that comes up especially as we move forward with new technologies and the NIH over the last decade has really emphasized implementation and so the combination of new technologies and implementation creates this essentially turbulent boundary sometimes that is where LC lives in a lot of cases there are a couple institutes that really they don't advertise a set aside but we can kind of tell from looking at what they do year in year F that they've they've allocated some budget for various projects yeah and I would agree I mean 5% is a arbitrary number 1% of the national cancer it would be a flood of money but yeah having that dedicated line would be great Eric do you have any thoughts about that I just don't think you're going to find a lot of enthusiasm for other institutes to get locked in on any number I mean I think it's one thing for them to start to get appropriately trained staff and areas of expertise and in some cases it seems like they're putting in a fairly consistent amount but I'm quite sure they want no part of a set aside or being locked in they want to stay flexible okay thank you very much Larry let's press on