 Thanks, Dan, and the other speakers. I'd like to ask the four speakers from this morning maybe to come up to answer and field some questions. We have about 10 or 15 minutes or so for questions from the audience. And I encourage you to use the microphones. So don't be shy. But I will start, I guess, particularly since I know that we probably don't have Francis here for the entire two days. I would like to just ask him from the perspective of someone who has led a very large and complex multinational project, the Human Genome Project, as you think about the potential for this group to do maybe something in the genomics implementation space at scale. What types of lessons learned? Or I wouldn't hesitate to call it advice. But what sort of insights from that project would you want us to be thinking about as we think about what we might do or might not do coming out of this meeting? I think it is an appropriate question. And we have some experiences from the genome sequencing effort, from HAPMAP, from now the International Cancer Genomics effort, from the International Microbiome Project to sort of see how those kinds of models have been developed. There are other things going on with rare diseases. So certainly it would be appropriate, not just in my quick response here, but in a more thorough way to look and see how those were structured and what seemed to have been successful efforts and which things maybe we could learn from and not make the same mistakes. I think the most critical thing is to create a space where talented, motivated, energetic, visionary people will want to come and take part. And that was critical for every one of the successful international efforts that I've mentioned. You want this to be a place where somebody really would not want to miss out on taking part in such an effort, because they know that the atmosphere, that the quality of the team, that the consequences of what goes on are going to be something that you just don't want to miss taking part in. That being said, it will be crucial to have leadership of the effort that is truly international, that recognizes the importance of having the contributions of all the participants really clearly laid out and appropriately credited so that people don't feel as if they're cogs in some machine. And particularly for this effort, it's going to take maybe more in the way of sophistication in managing all of the differences that exist in medical care systems across the world. That was not such a serious issue, although it occasionally came up in sequencing the human genome or even in HAPMAP. But here, it's going to be a big issue, just in terms of what kinds of access one has to specimens, to issues about a policy, and so on. I would urge strongly that the ethic that the group adopts, which has served so well for genomics, is this idea of immediate open access to the information that's derived, because that becomes so empowering. It is a little threatening at first for people who have not lived in that kind of space, because it has not been the tradition of medical research in many areas previously to be so forthcoming and revealing. But it turns everything into a much more interesting and productive enterprise to take that step. Recognizing that immediate release of the data does not mean that the producers of the data should have their contribution ignored or neglected or downgraded, but that basically, by making the data available, you're actually having the producers more important, not less so, and that'll be an important issue to consider. I could go on a bit, but those are some of the main principles to think about. That's those are terrific responses. Eric, did you look like you had something to add to that? Well, I mean, I think the only thing I would, I was going to immediately add, was just vehicles for communication. And I think maybe even more important in this regard, because, I mean, almost Terry started to allude to it. I mean, I just think the complexities of the heterogeneity of healthcare delivery. I mean, you know, Genome Project was very focused, goal laser focused in some ways. I think the concept of genomic medicine and how that gets implemented in different countries and different cultures and different ecosystems, it makes it even more important that whatever we do collectively, that there's just incredibly good communication that we're going to benefit from collaborative efforts. Excellent point. Hi, I'm Alex Sheldiner. University of Maryland. So there's I guess another kind of personalized medicine paradox related to the one that Dan mentioned that I thought maybe the panel could address. And that's one of a policy paradox. The fact that our U.S. healthcare system we're told that we need to be moving towards population health, healthcare systems taking on risk for populations and the maintenance of their health. And I'm just wondering how you all think about layering personalized medicine on this policy paradox. You know, Alan, I don't really have an answer to that except that so there's this, I'll be a politician and not answer your question, but answer the question that I think you asked or the question that the answer that I want to give. And that is there is this tension, as you know, between evidence-based medicine and personalized medicine. People sort of argue that they're sort of to, you know, like the North and South of magnetic poles they'll never meet because if you have evidence-based medicine you have evidence across the population and if you're interested in the health of the population then you ought to deploy certain kinds of medications widely across a population, for example. And personalized medicine has this individual flavor to it. I don't think that those are actually as diametrically opposed to as they appear on first blush and the reason I don't think they're opposed is because if we have evidence that personalizing care results in better outcomes then we ought to personalize care. And the challenge I think to us in Emerge and to everybody in this room is to develop that evidence base and it's really early, early days, number one and number two to figure out which variants really are important for implementation in a clinical environment and not. And I think that's where the gap is as I see it but I think that those are not difficult views to reconcile except when it comes down to actually doing it you have to have the evidence and that's one of the things that we ought to focus on. Maybe I could just add in that, you know, I agree with everything Dan has said and we are sort of trying to start little smaller and then getting bigger and so populations are big and clinical care is a little bit smaller but we didn't have time and I'm sorry that we don't to have Howard McLeod talk a little bit about his PG&E program which really is looking as Dan sort of alluded to across populations at very big differences in drug metabolizing variants. Hope I'm getting this right, Howard. And making recommendations on a nationwide basis to say, you know, the prevalence of the polymorphisms that really make it inappropriate for your population to be using. Isoniazid, for example, is so high in this population that it probably shouldn't be a first line drug. So those kinds of implementations probably are possible along the road. I think we're not quite there yet for a large variety of them. Dr. Alfala. So thank you very much. So I, as I understand from the genomic medicine one to five, the various American agencies founded hard to work with each other, at least that's my understanding. What is your vision for this an international consortium? What are we going to get out of this? I mean, of course there is a basic question which is a basic answer that we all gonna learn from that but what are our targets really? Do you have anything set in mind for all of us to work because it's gonna be a gigantic job? Right, so I might ask Jeff to comment. And he did review sort of what the outcomes might be. My personal dream would be in, sorry? Would be an evidence generation project on a large scale because we can actually get at the wide diversity of genetic variation and if we can use some of the electronic phenotyping tools that were described here, it can't be that difficult to try to get some phenotypes out of the medical records that we're all collecting worldwide. So that to me would be a dream but I don't know Jeff. I would just say that we would in want to be very proscriptive going into this meeting about what the output would be, thinking that our own provincial view of what the field looks like should not represent yours or any of the diversity of people in the audience. So I think this is one of our challenges for the next two days is to keep coming back to what are the opportunities? And think about things that would have near term wins that could really be a demonstration that we can act as a global community to do something impactful in this field and then go beyond that. I'm not saying anything very detailed purposely. I mean the kind of project that Terry alluded to an evidence generation project would certainly be something that I think we would all rally around though. Thanks for the question. We have time probably for two more questions. I think, I can't tell how many people are in line but we do need to also respect some of the agenda so let's go with Heidi and then Mark. So this is a question probably for Francis. As Dan mentioned and I think many of us believe the implementation of genomics into medicine is going to critically depend on electronic health care systems that we all employ throughout our hospitals. And being involved in the partners healthcare implementation of EPIC at the figure of $1.5 billion and being on the genomic medicine committee for that, we are struggling to even get family history implemented into an EHR environment let alone all of the things that all of us in this room want to do. And my question is what if any role does NIH potentially play in the EHR environment and how we interplay between private healthcare systems and other healthcare systems and the NIH that has such momentum in this space? So it's a great question and in the United States in terms of the standards that have to be adopted by electronic health records, much of this is overseen by the Office of the National Coordinator for Health IT. And we have close and regular interactions with ONC about exactly how in their various phases of implementing those standards they could be put in place in a way that is friendly to research. We have to be realistic about it of course because the main point of the electronic health record is to help care be delivered. And so if we layer too many things on top of that that really don't have much use in the management of patient care but are purely research oriented there will be loud objections. We've already experienced a little bit of that. But we are being given the opportunity by ONC to put forward realistic standards that ought to be included as this whole process evolves. And of course it is an evolving process. What you see now, thank God, is not what you're going to have in a few years if we continue down this road. So it is a great opportunity if this group, for instance, wanted to suggest things that electronic health records across the world really need to have in place in order to deliver good genomic medicine. I'd love to hear about that. Thanks Francis. Mark, and then short questions please. Yeah, I just wanted to come back to the first question about population health. I think it's important to recognize that we do this already. I mean, if we do blood transfusions we personalize blood transfusions based on a variety of blood types and we treat that in a population manner but we use that individual data. And I think a concept that needs to be thought about is one that Clay Christensen has put forward called precision medicine that right now we're in an empiric period of medicine where we say based on population you're likely to respond to this drug, we're going to try it and then we'll see if it works or if it doesn't work or if it kills you. But he's envisioning a time where we will be able to precisely define diseases, understand what the causes are and then target those causes with drugs that are specifically designed or work best in that and that you can still use population approaches but be very precise about how it's done and the principles that underlie that are mass customization which is why we can all get the laptop exactly that we want but we use mass production techniques to get high reliability and that's the transformative re-engineering of health care delivery that will allow us to do that. So I don't see this as a paradox at all but it still does come back to the evidence generation we have to generate the evidence to understand how to realize precision medicine. Thanks Mark. Just briefly this is for Terry, I was very interested in your name and Paul Lasko, Canadian Institute of Health Research. I was very intrigued with what you had to say about education of healthcare providers. This is a hugely important issue and I wonder if your group has any plans to take that program globally and engage international agencies. Well, we would love to do that. We'll need some partners in order to be able to and since we know you're right next door, that's good to know but yes, absolutely and we're trying to make as much available widely as possible and we should talk more about how to expand that. Great, and just let me add a comment based on the previous question by Dr. Alfalo about what we could do coming out of this meeting. We laid out the working groups activities as a menu of potential ways to expand them to an international community. Thank you. I'm Sinha from India. I was thinking about the whole vaccinology area. My question here is that impact of genomic medicine in future in the immunization program, whether it could have some impact and second point actually, which I would like to flag here that in India we have couple of new institutions where we have longstanding Indo-U.S. relationship. So we'll be interested, particularly in some educational and training programs. Thank you. Thank you. In terms of immunization, I'm aware that there is some work that the CDC has done. They initially started looking at smallpox, I believe and then at some of the flu vaccine reactions because there are some really devastating reactions to those vaccines. So some work is beginning, but it's discovery work and it needs to be done and I don't think there's enough of it personally. Yeah, there's this intriguing recent observation about narcolepsy and being a side effect of immunization for influenza in Scandinavia with a particular batch of the vaccine. And that's just a snapshot of maybe the way in which genomics and vaccination may find some opportunities to work together. Last question, Dr. Hubbard. Hi, Tim Hubbard from Genomics England. This question of coordination bodies, a lot of the potential of coordinating across the globe is data exchange. Now there's this other entity, the Global Alliance, which has recently been set up. It's obviously not completely the same thing, but if you've had something new, there'd be a lot of overlap between that. Have you considered how to work with that? So I'm glad you brought it up, Tim. So I think not everybody is aware because it's a new arrival on the scene, but it certainly should be on the table for this meeting. The Global Alliance for Genomic Health GA4GH, as it has now been rechristened, is an effort to try to establish standards by which large-scale genomic data sets related to human medicine can find their way into a shared data format, probably in the cloud, to allow investigators to gain access to such data sets and to make inferences and provide insights that might otherwise take a long time by trying to be sure that formatting is thought about, that privacy and access is thought about. This group now has a series of working groups that are pretty rolled up their sleeves trying to come up with standards. There'll be a meeting London on March 4th to see where we have gotten to. It is an international effort. Certainly, while you might think of this as sort of on the mechanical side, if we don't get this part right in terms of how data finds its way into an accessible place, then a lot of the rest of our dreams, as far as the research opportunities and their clinical implications, will be impeded. So I think many of us have been quite excited to see this arrive. Many institutions, more than 100, have signed on. Probably many of you in this room have institutions that have joined this GA4GH, but certainly something that needs to be watched closely. The next year is gonna be critical. And we were well aware of the relevance of the Global Alliance and this meeting. And in fact, the organizers meeting, we extended an invitation, just didn't work out scheduling-wise for some of the key people. But anything coming out of this gathering should clearly somehow make sure there's good connections with the Global Alliance. All right, well, I wanna really thank our speakers and our panel for laying the groundwork for today's and tomorrow's meeting. We're gonna take a short break, probably about 23 minutes or so. We'll try to be back here at five after 10 to keep on our schedule. See you in a few minutes.