 I suppose we should get started since it's now 8 o'clock. I'm going to introduce Michael Varner. He's a professor of maternal fetal medicine here at the University of Utah. And he's also the director of the Center for Personalized Health Care here. He's been the director of that for about a year. And his other claim to fame is that he's been married to Kathleen DeGreece for 37 years, to the extent that his daughters are intelligent and good-looking and prove that she's their mother. So when I was asked to give this talk, I thought, I'm going to go read the ophthalmologic literature, and I'm going to make this an ophthalmology-specific talk. And that didn't happen, actually. So if you're expecting that, then I'll apologize up front. But I have found myself on a steep learning curve over the last year with this whole project. And I thought it was a good idea to let you all know what's going on. And frankly, my thinly veiled motive is to try to engage the Department of Ophthalmology in this project, which it really hasn't been up to this point. So the first quiz question is this. What was the Carnegie Foundation's bulletin number four? And if I can make a Socratic response to that, it's what's now called the Flexner Report. And all of us basically in this room have been affected profoundly by that. It was really what introduced science into medicine, what some people might call the first revolution in medicine or medical education. They say people know about these things say that human knowledge doubles every 18 to 24 months, which, if that's really true, turns out that's not a straight line increase. It's an exponential increase. And we're now into something called the Zetabytes worth of knowledge. And I'm not quite sure how many billion billion that is, but it's a lot of information that we're accumulating on a year-to-year basis. And certainly in our business, all of our business in medicine, this ongoing, if you will, explosion combined with costs, which we'll talk about in a second as well, has really gotten to the point where we ought to be thinking about, people are thinking about, if you will, a second revolution. So in 1910, the state of the art was germ theory, chemistry, physiology, pathology, physics. And what we're trying to do in those days is understand disease, find it, fix it. And that's still the fundamental tenet of medical education. And by and large, of medical practice today. Nowadays, though, we've got all these other things, genomics, the omics, if you will, systems, biology, informatics, et cetera. And hopefully, the name of the game going forward is going to be predicted and personalized. I think I hope this is about as close to, oh my god, slide as I have. But historically, at least, we've kind of been over in this range of this curve. Where we can first detect something, where we first intervene. And the disease burden tends and costs both tend to be pretty high. And the theory, at least, is that we ought to try to shift towards, if you will, at least the earliest molecular detection, if not even back as far as trying to alter the initiating events. So people say, well, what is personalized self-care? And I've heard it said, well, it's kind of like pornography that I can't define it, but I'll know it when I see it. And I don't know if that's really true, but Jennifer Logan, who is my co-compadre in this project, and I have opted for this particular definition, the tailoring of medical treatment to the individual characteristics of each patient. Now, a lot of people think of personalized health care as being equivalent to genomic medicine. It is certainly, genomic medicine is certainly part of it, but it really has to be more than that. In essence, though, trying to provide the right intervention for the right patient at the right time and at the right cost. And my ventures to this side of the bridge, by and large, are bringing my wife lattes on neuro-optimology days. So I don't really know much of the day-to-day, I don't know anything about the day-to-day operations over here, but on the other side of the bridge, historically at least, cost has been a four-letter word in medical education and medical practice both. And I have been hurling myself on a sharp stick for a long time trying to find out how much anything costs, in at least around the University of Utah. It's a very closely kept secret and we need to come out on that. You may hear people talk about something called P4 medicine, which is a nice acronym that predictive, personalized and participatory. And this participatory thing, I think is particularly important and something that needs to be kept in mind when we're tempted to think about it as just genomic medicine. Because it turns out that if you're sitting on the sofa eating Twinkies all day, it doesn't matter what your DNA sequence is because you're gonna be way short on methyl groups. So the history of this around the University, the abbreviated version hopefully, is that those of you who are here, 2007, 2008, the institution spent a year with having a research strategic planning process to try to develop a plan for the next decade. The two things that kept bubbling to the top were molecular medicine and personalized healthcare. What the management chose to try to do is to recruit somebody to come in, help us set it up right. The number of people out there in this particular arena turns out to be pretty small, very small. And what happened basically is they had two people who had a pretty good job where they were come for several interviews, kinda get up to the 11th hour and then back out. And so I think what we ended up with was two people who had pretty good jobs where they were ended up with better jobs where they were and we ended up with nothing to show for it for two years. So I got a call to the principal's office back in about February of last year. And I'm happy to say I don't get called to the principal's office very often, but Dr. Betz made me an offer I couldn't refuse in terms of what I serve as a interim director for this project. So as of May 1st last year, I've been involved with this. And for the current fiscal year at least, we've had five program objectives which I'll zip through momentarily though, a lot of which it turns out overlap with the CCTS. And so we've had a collaborative agreement with them from the beginning. One thing I wanna tell you a little bit about was an online forum and a strategic planning retreat that we had last fall. And then also a little bit about a white paper that I was hoping would have been posted for general comments by now, but I haven't quite made it. So the objectives are basically these and it's really pretty much the usual suspects, but we had a grant, when we set this up for last year, we actually had several hundred thousand dollars on a one time deal both for pilot projects and for a genome exome sequencing. And at the moment we have 154 exomes in the process of being sequenced on six different conditions. And hopefully we'll score something big out of that. We've been, the program has been a supporter of the UPDV and I know that several of you have been involved with that but I wanna say a little bit about that in a minute. And then also something called the Utah BioHealth Initiative. This is a collaborative venture between the university and Intermountain to try to basically to figure out who's got what in terms of biologic samples. One of the advantages of working in a bottoms up economy like turns out we all do is that if you're paying your way you can pretty much do whatever you want. And that's the good news. The bad news is that everybody's pretty much doing what they want and there's not a whole lot of coordination. I mean I have my freezer farm. I'm sure there's some, I know there are some number of freezer farms in this department too where people have snippets of this or that. I bet I have, I bet I have, I don't know, pick a number, 50, 100 snippets of people that I've accumulated over the years who've also found their way into one of your biologic sample banks and there is no way as it currently stands that any of us would know anything about that, let alone who might have something over at Intermountain. Excuse me, from the standpoint of a clinical prospect, this is gonna be a longer haul but we're trying to, one of the things we're trying to promote is clinical pathways, clinical guidance teams, et cetera, interdisciplinary, that's supposed to be collaboration. I thought I'd found all the typos but I guess I didn't. And if any of you have spent any time in the Intermountain system, that looks an awful lot like Intermountain and that's frankly by design. If we wanna individualize things, turns out right now the bandwidth of who does what, where at least on the other side of the bridge anyway is so wide that you really can't tell where normal ends and abnormal begins. And so trying to decrease bandwidth on clinical practice is a, it turns out to be a very important issue, particularly with capitation around the corner, trying to figure out the hot spotting issues. You know again, the top 5% of people consuming an inordinate amount of resources. Clinical pharmacogenetics I know is an issue in every discipline of medicine and turns out those polymorphisms that affect my business, affect your business and we need to come up with a mechanism to track that. And then finally the whole issue of individual and community engagement because we're not gonna end the cost curve just by ourselves. We have an education advisory committee and we actually have a spring semester course on personalized healthcare that's being run through the K30 program. Hopefully it'll be more widely advertised, subscribed. We're working on curriculum offerings for the fall and also for a certificate program. And I don't know, have any of you heard of our personalized healthcare discussion groups that meet second and fourth Mondays at 515 over in the Williams building? Williams building is over in Research Park. It is by definition off campus and so one can have pizza and adult beverages at 515 on Monday if that's an attraction to anybody. We had a travel grants, happy travel grants program where we pay for some number of people this year to go to personalized healthcare meetings and we hope it'll sort of jumpstart some interest and we're planning to do that again next year. We have another program coming up that may or may not appeal to folks here but personalized healthcare and women and children's health in May and we're planning several more for this upcoming year. Probably in September to have a couple of day session about the UPDB. This year is the 30th anniversary of the executive order to set the UPDB up and so we hope we can not only open the gates a little bit wider but also have some sort of a fest drift about what's been accomplished to this point. We'd like to think of ourselves, Jennifer and I anyway, as a sort of a communications or information hub for the institution. We've been around to talk to an awful lot of people, 150 plus anyway, around the university, Intermountain, the community at large about what they think personalized healthcare is or could be presentations like this. Et cetera and again we hope we can be a information hub and the communications center. I mentioned the CCTS and again we have a lot of things of areas in common. We've had the CCTS review our grant submissions, the course that we talked about and at least one more coming up. You know on my computer screen Vivian Lee doesn't look nearly as pixelated as she does there but everybody knows that she arrived in July and one of the things that she, several things she keeps talking about, bending the cost care, personalized healthcare, increased collaboration with Intermountain. And when she was the dean for research at NYU she set up a program where sort of a web blog where everybody in the place could either list or comment on somebody else's listed topics for research ideas and people ended up sort of populating themselves into groups, working groups and it was very successful there. And she suggested so to speak and you know when the dean suggests it's always a good idea to listen that we do the same sort of thing here which we did and it was really quite remarkable. We had ended up with 82 topic areas, 450 some people offered comments and sort of more or less distilled to these same issues here. The one of the people at Ski at the Super Computing Institute has a little program that will scan through a word document and then list all the words, the size being the reflection of how frequently they're mentioned treatment, risk, information, genetics, the usual again suspects there but we had this retreat back at the beginning of December, end of last year. And so one thing I learned from this is that the term strategic planning retreat and the number 277 actually don't go together all that well. It's pretty hard to get granular with that that many people, we had attendees from a wide number of areas, all the health sciences colleges, a fair amount actually of the university and a number of cultural business communities. The one thing, two things that were notably missing here. One was the payer community and the other was the department of ophthalmology. So who was the only ophthalmology representative and it was kind of given away already, it was my wife and she was there because I made her be there to give one of the talks. And so I am hoping that if nothing else out of this hour that be successful in engaging you all in this project going forward. So the essence of it was we had a bunch of talks on Wednesday afternoon about infrastructure, about various clinical possibilities. And we ended up with these focus groups, there were nine of them all together looking at these topics and then each group gave a report that afternoon. But probably the thing that was most impressive to me out of the whole thing was the number of connections that were clearly established between people who were two floors down or up from somebody else or in the next building over who'd been here for however long and never knew that somebody else was either here or had any idea of what they might have been doing. So again, if nothing else, we hope we can help facilitate collaboration and communication on these issues. This white paper, again, I'd hoped it'd be out by now, but it was a summary of this whole process. And we'd like to think it's gonna take things pretty much down to the ground, but I'm gonna spend the rest of my time just kind of going through some of these priorities that came out of it, UPDD access, family history, pharmacogenomics, the consolidation of research databases, issues of health economics, comparative effectiveness, research, et cetera, point of care education, and then a little bit about multidisciplinary and specialty pathways in education. So if nothing else, this slide is gonna show up a few more times in the next few minutes, so it'll give you some idea of how much more of me you've had to listen to. I mentioned the UPDB, and again, it's been around for 30 years. There was a time, 10 years ago, where people could say, well, the UPDB and Iceland, and perhaps Sweden and Norway had the best genetic epidemiology resources in the world. And it turns out that, between Iceland imploding and relatively more effort being put into the UPDB, it really does seem as though we've gotten to the point of it being the biggest, the best genetic epidemiology resource on the planet. It's governed by something called the Resource for Genetic Epidemiology, which is a confederation of the major players in this, the university, the church, and the health department, Intermountain more recently has a seat at the table, and they, to their credit, keep a careful watch over all of their data. And to this point, at least, have not had a security breach, which is something that they're planning to maintain. But it's a really remarkable resource for looking at a whole lot of different things. And again, I know some of you all have been involved with it, and to the extent that conditions you all deal with could be intergenerational, to the extent that they can be cosegregated with other conditions. It really is a unique resource. It's not free, on the other hand. They will, if you're working towards a grant, perform at least a limited number of hours of work to try to gather preliminary data. Other than that, though, it ends up being a fee for service exercise. If you can collect your own data, or if you can analyze your own data, and they just provide it to you, it ends up being pretty economical. If they're gonna analyze it for you as well, it starts to get a little pricey. But you can come up with all sorts of things. This is a slide that I got from Randy Burt over at HCI, just looking at a family pedigree for colon cancer and colon polyps. And again, can look at all sorts of different things. Family history is another important thing that we wanna try to emphasize. And people say that genetics is family histories, or family histories with data, which I think is probably true. And the flip side of that, of course, is that most of the family histories that any of us in clinical medicine collect are not worth the paper they're printed on, because we only get, if we actually ask people in detail, we only get what they know, which is more often than not incomplete at best and with some regularity, not only incomplete, but inaccurate. So again, they're only as good as the questions that are asked and the information that is known. On the other hand, with current informatics technologies, all of us, at least who are engaged with a healthcare provider, have a problem list someplace. And I would contend that we can and perhaps even have an ethical obligation to have to do better than what we do. And that's, again, because we need these family histories to be able to utilize computerized decision support, which is something I'll talk about in a minute. Again, identify co-segregating diseases of all sorts. What would it take? Well, one is an appeal to families, which is something that probably sell better in Utah than a lot of other places. But if we're constructing a family history, an accurate family history, a complete family history, well, we're not only doing a service to ourself, but to our families in the future. On the other, HIPAA, which is actually HIPAA, that actually stands for how is it possible to accomplish anything, is a real issue in this sort of thing and we're gonna have to have people presumably opt in for sharing their PHI with other people and their families. And invariably there's gonna be, well, I don't wanna share it with my uncle John because he's a jerk and he owes me money. Or I don't want everybody to know that I'm HIV positive. So it'll be a big project, but it is certainly something that needs to be considered. And it needs to be a community-wide effort because if I get my healthcare at the university, but my sister gets her healthcare at Intermountain, well, then what good is that? We're not any better off than, even if we use my problem list, we're not any better off than where we were before. So again, no one health system is gonna be able to do this alone, but only by having all this information, accurate and complete information, can any family history tool ever be functional. Long-term personal histories are also important. I mean, not only from generation to generation, but long-term for me. I mean, what do the things that I am dealing with now portend for me in the future? One example, I don't know if it's Greg here. I don't see Greg. Anyway, Greg Hageman and I have had some conversations over the last year or two about this issue of co-segregation that women who have preeclampsia, it seems, which is something I deal with are, would seem to be more likely to show up with the macular degeneration 50 years later at your place. Any number of environmental exposures, gene environment, I mean, 25 years of living here, I still don't think it's right to see the air that you breathe. And Lisa, again, and I'm sure there are ophthalmologic effects of that. Premature labor is something that I deal with that comes and goes in relation to air pollution. And then finally, there's this whole issue of systems biology that the day, a lot of us got a lot of papers written about associations with this or that, SNP, et cetera, but it turns out that it's a lot more complicated than that and we're gonna need long-term personal histories, family histories to really sort the true complicated nature of biology out. So pharmacogenomics. All of us know that one size, the adage of one size fits all either in terms of diagnosis or treatment just doesn't hold water. One of the sort of the big, well, first off, oncology has been very much a poster child for pharmacogenomics in the past decade anyway. And that really got tipped off with this stuff called Herceptin, which is a medication that is very effective in women who have a specific protein on their breast cancer cells. And if you're unfortunate enough to have breast cancer and likewise don't have this particular protein, this stuff doesn't work really at all. So this has been sort of the poster child for this whole idea over the last decade. And it's brought up to this point has become a very big deal in Pharma's world, which is companion diagnostic testing, which is, in fact, the FDA just had a ruling back in July, the essence of which was that if you have a medication and evidence that there is a genomic marker that will identify who will or won't respond or who will or won't have adverse drug reactions that you're obliged to have that test run in association or at least prior to administering your medication. In oncology, there was a paper a few weeks ago now that just looked at SNP composition of tumors biopsied from several places at the same time. And the idea that a tumor was homogeneous kind of got shot out of the water at that point. Likewise, tumors develop resistance just like bacteria do. So this is gonna be an ongoing game of whack-a-mole, I think, but it's important to keep in mind for all these new things. A lot of different drugs that, again, we all use for different things and all of which have substantial rates of poor response, et cetera. The theory, at least, is this, that if we have some number of people with whatever diagnosis, that there'll be a group who either don't respond or who have adverse reactions and then we ought to treat them with something else. And then there's the rest of us who in fact should be treated with the appropriate medication. Adverse drug reactions is something that turns out to be a big deal. And I actually, I don't know how much of an issue it is for you all, but across the board, 5% of all hospitalizations are a result of adverse drug reactions. One in every 10 patients will experience one. 700,000 injuries, deaths per year, estimated approaching 100,000 deaths per year from adverse drug reactions. And you're in and you're out for the last 15 years since people have been keeping track of these things somewhere between the fourth and sixth most common cause of death in hospitalized patients and adverse drug reactions, it turns out costs more than the drugs themselves. So it's a lot of money. It's not easy to sort out because there's all these different cytochrome P450 things and a bunch of other different enzymes, et cetera. And in the world of ophthalmology, are there any of these that, I don't know if there are any of these that jump out in particular, but one of the things that we'd like to try to accomplish is to get us to the point where we can share information across disciplines about where the hotspots are, what the drugs adverse drug event issues are. A lot of challenges though, and it's easy to stand up here and talk about it. There's a lot of studies out there. Many of them are inconclusive. And it turns out that it's not just as simple as genetics that there's any number of other issues that go into explaining the variability for a given drug, some of which we know and some of which we don't. And frankly, when you get right down to it, very few studies still at this point that documented genotype-guided therapy is better than, if you will, the usual care approach of just trying to figure out as we go. One reason for that is that there really aren't very many point of care tests available. It's easy to say, well, we're gonna check this or that, but the reality is, if you have to draw a tube of blood and it goes over to Arup and it comes back two days later with this or that report, you've already ended up deciding what you're gonna do and it's gonna be something in hundreds of dollars anyway. So I have no financial interest at all in a company called DNA Electronics, but we're in the course of talking to these folks about a collaborative effort here and what they've come up with is a little device that you can spit into one end of it. You put the cap on first and then you mix it up and basically is some number of proteinases, RNA, et cetera. The other end of it has a USB attachment on it. You put it in your computer and in 15 minutes or so, it'll give you a report out of whatever steps you might want to program the chip for. Basically, collect the sample, slosh it around, put it in the computer and it puts out your whatever results you might want. I think at least, I mean we'll see, but it seems like it has the potential anyway to be a game changer because you can get results back in 15 minutes. You cut the lab out of it all together and so there's a substantial decrease in costs and it may well actually be a technology that's gonna tip us over the edge on this pharmacogenomics issue in the next couple of years. So stay tuned for that. Consolidating research databases, basically I think I talked about that a couple minutes ago, but again, if we're really gonna get to the bottom of some of these issues in a truly personalized and comprehensive fashion, we just have to be able to talk better, we have to be able to talk amongst ourselves about who's got what and where it is and how it correlates with. Likewise, in terms of health economics comparative effect in this research, people talk a lot, well we're all talking about bending the cost curve. One cost curve that actually has been bent is the cost per genome and this is just sequencing, but again, it was 1999, which is back here, was $3 billion for the Human Genome Project coming along here. We're down now to the range of a few thousand dollars. People are talking about the $100 genome. What they don't talk about is how to make sense out of all of that, but there's some rather substantial progress being made in terms of trying to actually at least look for causative genes for various conditions and pedigrees. The idea of the whole genome, here's my genome, what do you think Doc, is a little further out there because all of us have, and each one of us has some hundreds of thousands of copy number variants, indels, all these different variants of unknown significance that we just really can't make sense out of yet, but certainly the cost of the analysis anyway is decreasing. Now, here's another quiz for you though, just to demonstrate the magnitude of what we're up against. And these are the five largest national economies in the world at present, measured in trillions of dollars, which are thousands of billions, and it turns out that the U.S. healthcare system is the fifth largest economy in the world. A third of that is just waste or inappropriate treatment, but even if we knock that out, we'd still be the eighth largest economy in the world. And I don't think to say that that's just not a sustainable proposition. One of the other things in the program, personalized healthcare that we're trying to work on is point of care education. Just as an example, this is a program that actually the informatics folks here have put together, looking at warfarin pharmacogenomics and trying to come up with a point of care program that would help decide loading and maintenance doses. So it would come up, if we knew their SNPs already, come up and say, well, this particular person here might have an increased risk of bleeding complications and that they would need to either adjust the dose, monitor things, and so what do you want to do? You want to cancel that, modify drug doses, whatever. Besides all these, again, the SNPs here, there are a bunch of other things, up here, age, race, height, weight, et cetera, that go into it, other medications. And it comes out with a warfarin dose. And again, one place where this actually works pretty well right now at least is elected joint replacement of the people over at the Orthopedics Hospital who are actually doing this a fair amount. They have the luxury of being able to send this off on somebody a week before their surgery. If you show up with a acute PE in the emergency room, we'll send it off as you can still do it, but it's not going to be at this point at least not as helpful. So it comes out with an estimated dose, a loading dose, could say, well, here's how much you need for today. Are you taking any of these other medications that might impact the genotypes if you've been on it for a while? But the point being out of all of this that it has at least the potential not only to educate us and our patients, but also to try to minimize prescribing errors. Computerized decision support is clearly on the way here. All of us are being, will be obliged to utilize this technology with the inpatient and outpatient records. A lot of different things that it can potentially do. Alerts, reminders, remind us of clinical guidelines, pre-specified order sets, et cetera. Again, diagnostic support and point of care education. Patient education is clearly going to be an important issue too. Not everybody out there realizes or understands how much this whole system actually costs. In terms of getting timely results back at least, there's a educational opportunity there that patients can understand how it is that their therapies are being individualized that they can see the consequences. And for some things, could potentially get results confidentially. The issue, one of the things that's clearly going to be coming up more in the next year around the institution is the idea of some form of multidisciplinary pathways. And to be perfectly honest with you, I'm not exactly sure what form that's going to take. Dean Lee, the He-Lee, not the She-Lee, is very interested in looking at clinical pathways from the standpoint of drug diagnostics device developments. Jennifer and I are somewhat more interested in looking at multidisciplinary approaches to common diseases and problems. Pretty much every clinical entity, clinical department deals with diabetes, but we all deal with diabetes in our own separate way. We don't necessarily know what the guy in the next clinic down the hall or across the bridge might be doing. And so from an educational standpoint, that's going to be an important issue. And then the last thing to talk about is education. Josh Schiffman, who's a pediatric oncologist, is serving as our education committee chair. I mentioned we have this course going on this spring. We'll be offering again next spring. We're working on a certificate program and, again, the pizza and adult beverage discussion group will be starting up in May. I think the first one is May 14th. And again, we're trying to get out and talk to folks about this issue. It is important. It is pretty clearly the way forward. It's Vivian Lee's idea of the way forward. And so we need to at least know what's coming. So from our perspective at least, we think personalized health care is going to involve a paradigm shift towards individualized care that we hope will maximize health and minimize both morbidity and unnecessary costs. We think it's more than genomic medicine needs to be more than genomic medicine. And that it's going to represent a commitment not only by the entire Health Sciences Center, but the Utah community at large and for that matter, the country. And one of our sort of mantras in this whole thing is that we are actually now all in it together in the days of individualized silos, if you will, not only in terms of research, but clinical practice, really need to be reconsidered. So, anyway, this is my contact information. Jennifer Logan is my partner in crime and Connie Barth is the person who really keeps the wheels on things. We have a list serve for these discussion groups and other things in terms of upcoming events. If any of you are interested in that, well, the best way to get on it directly is to just send an email to Connie. If you have any questions about any of this stuff, well, please feel free to give me a call or send me an email anytime and I'm happy to talk about this for I bet longer than any of you would care to listen. So, thank you for your attention for letting me come and I'll be happy to answer any questions. Stunned silence. At any rate, thank you.