 Okay, great. Thanks. We are a very small group and we have protected our smallness by the fact that we went to the wrong room last night. So I want to apologize in advance for those people who went to the correct room and never found us. Two of the people did find us, but it was Mark's fault. We followed him. This group, from once we came, we used to be the miscellaneous group, which is a very uninviting title, and initially a lot of the topics were kind of IRB-ocentric. We escaped that trap quite quickly, thinking that that belongs everywhere. And we've evolved to this clinical research interface, which is sort of everything we're talking about. So our goal is the following. To explore the boundaries, what are they, where are they, how do they overlap, what do we know about each side and the middle, realizing it's not just a black and white, it really is a spectrum, is genomic information different from emerging clinical, other clinical information technologies, and is there a relevant research agenda that we could really identify for the space? Why should we do this? Because if we don't, we think the boundary is going to become a gap, and we don't think we are right now where we'd like to be. And where we would like to be is here, a knowledge-driven ecosystem. I love that term. With open sharing of ideas and problems, complementary efforts between everyone, maximizing output, advancing health, and everyone loves us and gives us money. But and so within genetics or genomics, where this would ideally be, is that we'd have robust collaboration with clinical contextualization, researchers working on problems and course correcting and concert and feedback with clinicians, clinicians anxiously awaiting research results and actively incorporating into their care, quality processes for communicating appropriate results, and seamless bi-directional flow between clinical and research. That would be nirvana. And I, we wanted to make it clear that it has to be in both directions. There are going to be in the clinical setting where I definitely have findings that need to be bumped back to research and we're really going to do a disservice if you just keep those in kind of the clinical node. And I think this gets to what David was suggesting in terms of return of research results versus disclosure. I think we have to, this is an area I think we need some better terminology and better understandings there. But even with this bi-directional flow pattern, there's very important modulators. There's patients, there's advocacy groups, local institutional pressures, a variety of industries, and here I mean not only big pharma and device, but also third party payers, research funding and laws and strong suggestions from those who give us the laws. So it's not, I think the slide we had yesterday where you know that the adoption of that test went way up until something happened. I mean this is, as you can imagine, it's not a unifactorial thing. But instead of where we'd like to be, where we are is this warp speed and it keeps going. There's difficulty with technology and this avalanche of what is seemingly more and more uncertain information. And while maybe many of the folks in this room can keep up, those who are not spending their life in genetics have a really hard time. And I know everyone had a quote, my quote is from our own Machiavelli. Anyone who thinks they understand it all is delusional. And this is from our committee member with the first name of Mark, of whom has many friends here. So what are the gap inducers? What is really pushing the boundary apart? First of all, the way we present genetic data is not very friendly to those who aren't living in that world. The uncertainty really drives people apart. Many clinicians, I'm being very black and white about clinicians and researchers just trying to push the extremes. But as a clinician, you want to know, do I have to act or not act? And this kind of, well, it might be important, maybe check back in a week. Well, you know, it doesn't kind of fit, particularly if it's multiple results you're getting the same way. There's a concern that genetic owows coming from the labs fail to consider the importance of environment, particularly when we look at all the HIPAA issues and identifiability, environmental things are really hard to keep on there, as well as the clinical setting. Again, this lack of clinical conceptualization, and oftentimes the findings have no relationship to what clinicians feel are the pressing problems. Other gap inducers, the impression is that the focus is how do we get this into the medical record and clinical practice rather than should we, and when should we. And there's also this issue of the evolving role of the patient. In terms of what are the expectations, direct to consumer genetic testing. This is the only place we put social media. We are very flattered that many of you thought social media should be ours. We have very consciously said no, we don't think it is we think it if anything belongs on its own somewhere. But people are finding out more. And I've added here also this medical record transparency because as things do start migrating to the medical record, what is happening is medical records are available to patients as they should be. But what some clinicians are finding is that you get a call from a patient saying you never told me that my serum calcium was abnormal. And you look at it and it was, you know, 10.3 and the high normal was 10.2. And the clinician is now being asked to address this. So just think of adding on and here is your entire whole genome sequence and we you're going to have people who are then going to mind that and be calling consistently. So again, that interface is a changing one. So we felt the gap needs to be better identified and ideally to look for where can we do some work. The gap we must avoid. Here is the geneticist. Wow, look what we've discovered. And here's a clinician and you think I care because and how do we avoid that. So what I've done and in this I have actually added bench researchers and clinicians. But I think everyone here has an adequate ego to realize that there are a lot of people in the middle and I'm just trying to make the extreme. So if I, you know, hurt anyone's feelings, get a life. So the gaps I'm going to talk about are there's the number of different ones and they kind of overlap. So I'll just go through all of them. And I agree that many can be put in different places. But in clear terms of the clinical context, bench researchers limited or no experience of interacting with patients do not appreciate the complexity of taking samples or data or communicating what the risk is. We are seeing an increased number of PhD trained without any clinical intervention, they can just buy tissue online. And they have never really had to talk to somebody. Clinicians on the other hand have kind of the fiduciary responsibility to their patients. They are being overwhelmed with pet with questions from patients. And they really serve as the information filter. Bench research that many researchers overrate their own research and lack big picture context. Clinicians await guidance from institutions or subspecialty societies and are very suspicious of individual Oh, wow. Researchers oftentimes have a simplified view of what it takes to get something into practice, whereas clinicians understand it immensely. And I do think the issue of reimbursement is much bigger than what the third party payers were saying here yesterday. It's not just on tests, it's on care. I mean, you can't steeper to ventilate a kid at home, long term care, but you can't get an insurer to cover the nurse that long term care. So you take up that money in an ICU. So it's not just with it's very complex. Still within the clinical context, even here, we've heard it's be great. You'll have the whole genome sequence. This can be used for life. Clinicians I order specific tests to rule out a candidate diagnosis that are relevant to my patient at that time. Uninvited information is not welcome. Whole genome sequencing can limit diagnostic crusades. Clinicians will say uninvited information causes diagnostic crusades. Clinicians who will provide the pre testing counseling as well as the post testing counseling and remember someone yesterday showed a slide that said when clinicians were asked non-genetic clinicians, 72% scored themselves as having a poor understanding of genetics. And yet these are the people who patients are coming to. In terms of motives gaps, on the researcher side urgency to move research findings forward, perhaps into clinical care. I think we're funding is now going with a focus on translational medicine, yes into clinical care. Clinicians again are waiting for that robust evidence for change and they have little time, energy or expertise for looking at all these one offs. Basic researchers urgency to prove the importance. In some cases, your institution may push you. This is really important. Let's get a patent. There's that was whole issue which we talked about. Clinicians feel there are all these rules and regulations and legal issues. This is in the chart and it's not really a valid test. What if a lawyer finds it? What if an insurer finds it? Basic researchers, here's my great result online to the next thing. The next thing for the clinician is the patient who's been in the waiting room every 15 minutes. The time issue is huge. The genetic information gap. Again, in for a genetics is different, both sides, I think feel that way. I think many people in this room, this is the most important information we have. Use it now. Clinicians genetics is overhyped. And I hear is the soccer quote. Soccer is the game of the future and it always will be. A lot of clinicians feel that way with genetics. Again, if it's that important, someone I wouldn't be paid for not doing it. The researchers, this is really great. You get a one-time whole genome sequence and you can look at that for the whole lifetime of the patient. Clinicians, you expect me to look at something that was obtained 20 years ago. I probably can't even find it. It'll probably be on a different IT platform anyway and won't be able to read it. I'll just repeat it. That's, you know, we got to get away from that. And again, clinicians liability concerns for omission and commission and big issues about what can and cannot go into the medical chart and who can and cannot put stuff into the medical chart. I think that's a changing area. Bad press. Researchers, clinicians know nothing about genetics. Clinicians, researchers have no concept of clinical care. There's a process for assessing new findings. All of their findings are not earth shattering. Researchers, we need to develop genetics for dummy's courses. I have heard this so many times. You're going to get a good number of people coming to that one. Personalized medicine on the clinician side. This is what we do. It's off-putting to think that genetics has identified this as a concept. So do I practice impersonal medicine if I don't use the whole genome in my? And this is actually from talking to Sutrinidad who works with Wiley Burke. They did some interviews with primary care physicians. And the amount of, you know, they're they're pissed. It's like, you know, don't talk to this for stupid. It's just not our area of expertise. And they hate the concept of personalized medicine. So suggestions. The last slide, I think we've heard this mantra many times today. A lot of people are in this space. We need to collaborate. We do not want to duplicate. In fact, our little working group is very happy to go away if this is being done elsewhere. And that we don't think we need duplication here. I do think we need to better understand evidentiary medicine and the process for routinizing it into clinical care. What standards? How is it triaged? How is it communicated? I think, you know, Paul just made my wish I hadn't put development guidelines, but he just said they're never good and they're never used anyway. But how do people decide what to do? And a lot of the talk we've had is institution-based. I think when you talk to clinicians, you know, I was in pediatric ICU medicine. And I don't so much care what's happening at Mass General. But when I go to my critical care society meetings, if we're the only people doing that, it's a little nerve-wracking. So I think we have to more look at subspecialty societies and get away from the siloing of individual institutions. What do clinicians need? What do the systems need to support the clinicians? And a lot of this is not only how to store and how to access the information, but also the whole counseling issues. What do patients expect? And again, I think that we are getting a much more informed, but maybe not knowledgeable patient base. They have a lot more data, but I'm not sure they know what it is. I think we need to better understand the medical chart and process, legal and institutional considerations, downstream implications, not only for following up on information, but also who can now access this. Maximize, and this is Paul, is one of the people who was able to find us last night. Maximize collaborations for clinical trial genomics. And this is essentially without repeating exactly what Paul was referring to. Look for those opportunities. And it would be in that interface. And if we were to, hey, Babel, have some wins in that space, it might, you know, do a lot for both sides of the street. And then finally, this is borrowed from work that Laura and Brad at all have put together. And they have a much more detailed thing. But it's just an attempt to look at just four things. And we're not even on there as a group. But you know, CESA, the Return of Research Result, Return of Results Consortium, Emergent Page. A lot of people in the informed consent area, a lot in the actionable variants, sequencing, phenotyping, electronic records, instruments and measurements. And if you look at our group, we're kind of in all of these also. So I think what really, really need to do is where do we cross-fertilize and not have siloed conversations. So I think I went at warp speed, but Terry, you know, you always get nervous when they said, how long are you going to talk? So I said I would talk very quickly. So happy to take comments or if members of our group want to add or think I got something totally wrong, my ego can handle it. And I again apologize. I think there's two people who tried to find us and were unable to. It was Mark's fault. Although we followed him. Okay, we're, Jeff. Thanks, Pearl. One of the ways that has been used to address at least some of the gaps that you measured between the bench researchers and clinicians has been the Howard Hughes Medical Institute's Grad and Med Initiative. I'm just, I just wanted to make you aware that there are some ways that some institutions are trying to educate basic researchers about the world of the clinician, but I really doubt the genetics piece is really a strong focal point of that, and perhaps that's one area to explore on the forward translation side. I don't know about the equivalent for clinicians to learn more about the life and issues around bench research. I think, and again this last slide is just only what is looking at NHGRI. I think to expand this to NIH in general as well as other places. I know like University of Washington has some good physician education programs, but I think what we need to do is, as a group, identify are there pieces that aren't being covered by these others and then to branch out what are other resources out there. I think there's a lot of people worried about this space, but I think we just need to amplify the level. Okay. Just a quick comment and I'm not offended at all by your separation of basic science lab science from clinical, but just can't resist the comment that I'm pleased at the increased number of attendees and participants and presentations by the laboratory directors who are the bridge category that I self-identify, so this is totally biased, as the ideal bridge usually being people with strong laboratory research training background whose then professional career is clinic the bridge and interface between laboratory technology laboratory findings into clinical medicine. And in a lot of meetings I go to they're not present on the invitee participant list. They're not presenting and so the gaps are huge when you don't have that group represented, but that's what we do is bridge between the new technology, new information on the basic science laboratory side where those researchers often don't have the clinical training and exposure, but we interact with clinicians and with patient data every day coming from a research training background, so that's... You realize that most people in this room don't realize that my first boss when I got NIH was David, so you can see how his brain washed me, but I agree with him anyway. That comment just can't be followed by anything. Titular, his first titular boss. One thing, I'm going to say a very short comment about that I think that what we're talking about is actually part of a larger issue. So the people that we really think about bridging the space are physician scientists in many ways and there's a really a dearth of young physician scientists coming up through the ranks and I think that's something that we need to think about how we're going to encourage that group of people who can help build those bridges between both research and clinical care because most of us who are physician scientists, this is what we do every day. One thing that people might want to keep in mind that our writing grants or funding grants or reviewing grants, we're getting a lot of pushback and I think it's rightful from our primary care providers who, you know, the assumption has always been that we'll generate this data, it'll be delivered in the clinic and that part is free and they're telling us very clearly that that's not free. Just a comment, you did show the clinical and the research going in both directions but I think that most of what researchers think about is the one direction and I think that the clinicians have to be engaged very early on, it goes back to what the payers were saying, to actually be doing research on clinically relevant questions and that is a huge problem. They have their field of science that they want to work on and they're doing discovery but they aren't targeting any clinical question that needs to be addressed and I think that link-up has to happen really, really early, even before grants are submitted and I don't know how you do that but it's got to be done. Okay, do we still have time? Are we? Well, we're late anyway but so make a comment and then we'll... Jeff, the hard use program you mentioned was that PhDs getting clinical training. Yeah, just to comment on your comment and Kate's comment. Although I've always been and will continue to be a big fan of physician-scientist training and funding mechanisms, I think there's always been a huge inequity in funding efforts in the opposite direction, the hard use program being an exception. NIH has done very little to train PhDs in clinical areas so in the success rate of physician-scientist training and retention in research has been miserable, it's still miserable and I haven't heard any good new ideas how to fix that. There's an overabundance of highly trained underemployed PhDs in the world, it's a huge labor pool and a huge majority of PhDs who have never been exposed to clinical training or settings would love to be more involved in clinical research. So it's this huge opportunity that I've never seen NIH seriously address. And if I could just add a quick additional comment, I run a clinical molecular genetics training program at Harvard to take PhDs and train them in clinical laboratory genetics and the challenge is, and this is true across the entire U.S., there's no funding for that opportunity and I turn away over 50 applicants every year who want to do this and we have no funding to do it. Pearl, we'll get the last word. Oh good, another negative word. And I think on the flip side from the physician side, I think the way we're going with training with the 80-hour work week, you're kicked out of the hospital, I think any opportunities for beginning the interaction with researchers is drying up and I completely agree that that group of people are the ones who currently are doing the best job and, you know, for a multitude of reasons we're losing that group. OK, so the schedule says we're close to a break, but what we're going to do is we're going to hear from Howard McLeod now.