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Vagelos Scholars Program in Molecular Life Sciences

From Wikipedia, the free encyclopedia

 Roy and Diana Vagelos Laboratories
Roy and Diana Vagelos Laboratories

The Vagelos Scholars Program in the Molecular Life Sciences is an undergraduate program at the University of Pennsylvania, named after Penn alumnus and Merck CEO Roy Vagelos (class of 1950) and his wife Diana.[1]

The program is directed by Dr. Ponzy Lu, Co-Chair of the College Biochemistry Program.[2]

Roy Vagelos donated over 15 million dollars to the University of Pennsylvania in order to create the Roy and Diana Vagelos Laboratories, located in front of the chemistry labs on 34th Street. This money also went to creating the Vagelos Scholars Program in Molecular Life Sciences, an intensive program offered to incoming freshmen attending the University of Pennsylvania. Each May, the Roy and Diana Vagelos Science Challenge Award, equal to the current tuition and fees, is awarded to approximately five outstanding undergraduates within the program.

Focusing on the core principles of chemistry, mathematics, and physics, students are required to take at least five courses per semester en route to either 1) a double major in two sciences, or 2) a major in chemistry, biochemistry, or physics and a submatriculated master's degree in the same subject. Included in the program are two paid summers for on-campus research.[3]

The Vagelos Program began in 1997 and has graduated sixteen classes as of 2017. Of 239 graduates between 2002 and 2017, 92 have attended PhD programs, 89 have attended MD programs, and 35 have attended MD–PhD programs.[4] With normal attrition, only about ten to fifteen students graduate from fifty entering students.[5]

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  • Presentation by NHLBI Director and Discussion - Gary Gibbons

Transcription

Eric Green: So let me introduce our speaker. And, Gary, you could slowly make your way to the podium while I embarrass you a little bit. So I'm delighted to introduce to this council the newly arrived director of the National Heart, Lung, and Blood Institute, Gary Gibbons. By way of some biographical background, Gary was the founder and recent director of the Cardiovascular Research Institute and chairperson of the Department of Physiology, a professor of physiology and medicine at Morehouse School of Medicine in Atlanta. Prior to joining the Morehouse School of Medicine in 1999, Gary was a member of the faculty at Stanford University from 1990 to 1996, and at Harvard Medical School from 1996 to 1999. He is originally from Philadelphia. He earned his undergraduate degree from Princeton University, and graduated magna cum laude from Harvard Medical School in Boston. He then completed residency and cardiology fellowship at Harvard-affiliated Brigham and Williams in Boston. I'd also point out, where I most specifically got to know Gary was as a member of the Board of Scientific Counselors overseeing our Intramural Research Program, where it was just wonderful to have him help us in our intramural program and get to know us. And that was a great introduction. And then when Francis was successful at convincing him to come take this important leadership position, we all cheered loud. At NHGRI it's wonderful to have a good friend and colleague at the helm of that important institute. And it's wonderful to have Gary here today to do -- to give a bit of an introduction. And I already know there's going to be some interesting discussion of things we want to talk to you about. Gary? Gary Gibbons: Okay. Great. Well, thanks, Eric. I appreciate this opportunity. I do feel as though I'm coming back to talk to family, to some extent, the degree to which we engaged this institute in the BSC. And I thought I'd paint a broad picture, predominantly, at the 25,000-foot view of what we're seeing in my first six months about a strategic vision, and hopefully a lot of opportunity for collaborative synergy with Genome, again, based in part on shared interests. First, that part of the conversation I had with Francis when -- particularly, people in this group would know how compelling and convincing Francis can be when it came to thinking about taking on this position, particularly, in such a challenging time as we're in. But it resonated with my sense of purpose and commitment to service. I very much had bought into the mission of the NHLBI as a longtime investigator and advisor and council member. And certainly, as part of my career development as a physician, as a scientist, as an educator, and as someone committed to public service, I do consider this a privilege to join the ranks of such a great organization. And I'm reminded that, in this role of public service, it's one of stewardship. And I took to heart this quote. It's a Native American proverb that reminds me of our stewardship both as a scientific enterprise and the biomedical workforce that we're stewards of. So I'm inheriting one of the oldest institutes that's enjoying its 65th birthday of stewardship and legacy, and I take that very seriously. And it's brought home by this quote that, "We did not inherit the land from our ancestors, we borrow it from our children." And it's that sense of stewardship, particularly looking forward to the future of the scientific enterprise and the next generation, that grounds me in terms of the decisions we have to make and, certainly, the decisions you make as part of this council. And with that sense of legacy and stewardship is a commitment to certain enduring principles that will guide the kind of decisions and priorities that I will set forth. One is to value and support investigator-initiated fundamental discovery science as really a bedrock foundation, that I know Eric and this institute has always historically had. Similarly, particularly important for NHLBI, is to maintain a balanced cross-disciplinary portfolio that has traditionally spanned -- I think relatively nimbly -- basic translational clinical and population science. And I think that balance is critical for the constituencies and scientific interests that are a part of our institute. Another element that I think is important for the NHLBI, as part of its legacy, really, is part of our congressional authorization, indeed, mandates a certain outreach effort in implementation science that empowers patients, and providers, and systems to ensure that, in fact, we're having a public health impact, again, related to our particular portfolio of heart, lung, and blood. And so we find ourselves more and more in the implementation space than perhaps other institutes. Though, again, I was excited about the app that you guys have for understanding -- helping the public to understand genomic science and genetics. And Eric knows that in a recent trip with my daughter, she was actually giving him all kind of kudos because she's already downloaded the app. So I think that's actually part of our role as well, is to be able to inform the public critically about what we're doing. Indeed, I think that's critical to us sustaining it, particularly in these fiscally challenging times. The other enduring principles are related, again, to an element of the portfolio that I'm particularly passionate about. And that relates to the diversity of the biomedical workforce, and that we need to train and nurture this new generation to be the leaders of tomorrow. Similarly, an enduring principle that's particularly a priority for me is that not only do we have public health impact in the United States, but around the globe. And we do that to communities that, quite frankly, don't have all of the most optimal health indices that we'd like to see in the space of heart, lung, and blood disorders, and to address health inequities. Critical to this -- and this is really the first part of my talk -- is that stewardship about the next generation. And in that regard, what you see here is a pie chart that shows the U.S. population here on the left, and -- increasingly becoming demographically diverse as we move forward in this century. And then the pie chart on the right, you can see our NIH PI grantee distribution. And you'll note that these generous slivers for the population in Hispanics and, particularly, African Americans -- indeed, the same could be said for Native Americans -- become -- go from relatively healthy slivers to tiny little slices that are barely perceptible on the pie chart. And that would be one of the things, I think, is part of our challenge. But also opportunity moving forward is to move toward our stewardship of a biomedical workforce that reflects the diversity of this nation. I'm a firm believer that excellent and talent is not bounded by gender, race, or ethnicity, or national origin. Indeed, I would argue that that's what made the United States of America the great nation that it has been over its history, is that we've taken the best and the brightest from around the world. And I believe firmly that we can pursue excellence. Indeed, our pursuit of excellence will be enabled by ensuring that we tap all the talent in this country, and we have some work to do in that regard. Some of it has been a rude awakening. As someone who's had his intramural program bounce around to a number of different institutions, one of the things I found when I arrived here is that my arrival meant a dramatic increase in the proportion of African-American tenured professors -- tenured investigators in the intramural program. And so, indeed, as the NIH ascends to the bully pulpit on this issue, we recognize that we have our own sort of glass house challenge in addressing this internally. And although I'm sure many in this audience chuckled, I suspect that as you go back to your own institutions around the country, that these statistics are probably not dissimilar to a lot of the top institutions in this country. And so this is a collective challenge that I think we have as all leaders in this room, to ensure that, again, we're tapping all the talent of this diverse nation. In that regard, I've had a little bit of experience in thinking about what it takes to grow up a generation of minority scientists. I've been blessed in my career to encounter some great folks along the way that helped me tremendously. One of the things I've appreciated -- and this is universal -- is that there's certain things about developing any scientist, and it all begins with passion in my view, that fire in that belly, that intensity to be curious and to pursue science that's critical to success of any scientist. I actually think that it's almost an article of faith, quite frankly, for minority scientists in particular. This notion that you're willing to step out into something unknown, that maybe no one in your local circumstance -- your family, your neighborhood -- has ever even conceived of as a possibility of a career, in my experience, requires something of a step of faith, and a willingness and courage to seize opportunities in that space that's so uncomfortable. My view is that if there is a underrepresented minority individual who is willing to have that passion, that faith, and seize that opportunity, it's incumbent upon us to match that and meet that with providing that opportunity. And in that regard, I think that's something that NIH, in its public responsibility of this public good for the nation, is somewhat accountable for. To borrow yet another proverb of an ancient people, that's an African proverb that "It takes a village to raise a child." And I believe that's also pertinent to changing that pie chart. That inevitably this involves a collective action of the village, including the people around this table, to make a difference in this regard. A key element would be mentorship. I actually think that that's the determining factor; certainly has been a determining factor for me and my career trajectory. I wouldn't be here standing before you if it wasn't for a Harvard professor named A. Clifford Barger, who inspired me to even think of doing this, because I had no idea I was going to do that in my first year of Harvard Medical School. And so I think that's critical. And I think everybody around this room knows how critically important this is, and finding the resources to excel. And so one of the kudos I have to give Francis Collins, as NIH director, is that, in recognizing this, he put together an ACD working group. And as fate would have it, he recruited me to be a member of that working group. And as it turns out, that was a very slick recruitment tool -- [laughter] -- because I went from being on the working group to being now in the implementation group as now someone who's transitioned to the inside and the Diversity Council. Francis is a master at these things. And so part of his initiatives that will come out of the Common Fund relate to trying to address this. And so I hope you will, as leaders, stay tuned for initiatives that are targeted toward addressing this challenge collectively. A number -- well, one key one that I hope you will take very seriously to participate on will relate to mentorship and this notion of creating a national network, and to leverage the fact that we are in a social media and social networking context, and figuring out how we can do this more effectively, particularly for underrepresented groups that may not have access to the best mentors and mentorship. Now with that, I do have this notion that this is a problem that's been vexing. But I have hope. And there was a time when we didn't think that there would be a monument like this on the mall, or that we'd have a president who looks like President Obama. I think, at the least, the modern medical workforce can make that sort of transformational change occur with collective leadership. With that -- the community that we're a part of -- let me pivot more toward not only the stewardship of the workforce, but what we'd hope to do as stewards of the scientific enterprise moving forward, that, again, I think I'm privileged and blessed to inherit a great legacy of excellence. I think it's arguable that Heart, Lung, and Blood has been a leader in translating research results and discovery science into major public health impact. Although the NIH can't take full credit for this declining curve of cardiovascular mortality, clearly it's been a key contributor with scientific discovery. And the challenge really is for us to continue to, what we call, bending this curve even further to reduce those events, that this is to be part of what the NIH should have as one of its outcomes. And it's very helpful to think about how that success was achieved, at least as a model of how we can move forward over the next 10 years. And just a couple of quick lessons. This is a detailed slide, but it's illustrative of the success we've had in the cardiovascular area that resonates with me as a cardiologist, in which, arguably, you could say that the population scientists were critical in framing the challenge of heart disease. And particularly, the almost iconic Framingham Heart Study almost invented -- I guess, practically did invent -- the term risk factors for disease in identifying cigarette smoking and cholesterol and hypertension as major drivers of this, and critical to have that sort of population science within the portfolio. What it also implies to me is this sort of interaction that has occurred in which population science has often identified certain associations, but that gives opportunities for clinical science and basic science to help fill in either the causal links or some of the connections. In that regard, I think it was notable that the NIH Intramural Program had a robust role. That picture here is Don Fredrickson in the Intramural Program, who was actually at the clinical center identifying, basically, clinical phenotypes of lipids, the biomarkers of the day, in subcategorizing patients as a means of then doing deeper dives to understand the molecular basis of those clinical phenotypes. And again, there's sort of paradigmatic echoes for what I think we need to do moving forward. The second piece of this intramural component was, again, the notion that Fredrickson also, as part of his clinical center involvement, came across a child with these swollen orange tonsils, and described Tangier's Disease. And it was interesting that Eric cited Bill Gahl's work in looking at rare disorders, and at how important that has advanced things. And, indeed, that is a rare disorder in which now we know the molecular basis of it in terms of ABC transporters. But all that began within the context of the intramural program, and, again, is a lesson, at least for me, as we move forward to continue to leverage. The third point there is that -- pictured here are the Stadtmans. And it comes back to this concept of stewardship of the next generation, and mentorship in the fact that, particularly at that point in time, the intramural program played a critical role in preparing the next generation. And, indeed, also pictured on this slide are Brown and Goldstein, who need no introduction, and Roy Vagelos, who had moved on to lead Merck's efforts in this space. And all three of them were fellows in the context of that same intramural program, and actually played a critical role to this whole story of how we went from cardiovascular risk factors to changing coronary artery disease, in which the observations in population science, the intramural program fed into basic science laboratories, like those at UT Southwestern, to come up with the characterization of the LDL receptor, familial hypercholesterolemia, and the LDL receptor mutations, HMG-CoA reductase as a target molecule for therapeutics, and on and on. NHLBI then funded clinical trials to translate that into clinical practice, partnered in a complementary fashion, if you will, with private industry -- not so much to drive drug discovery, but, again, to provide the basis for it in basic science discovery and clinical trials; and, finally, implementation science, to disseminate an understanding to the public of the importance of cholesterol control that continues to this day. And so I walk through that success story because I think it does provide a paradigm for us moving forward to continue that sort of balance, and approach an interaction between our various portfolios. Part of the reason why I actually did listen to Francis and take on this position in these challenging times is because of the infectious enthusiasm that I think we all share. That, at this particular moment in time, we actually have some of the greatest -- we're on the threshold of some of the greatest opportunities to pursue. And so despite what's happening or not happening on the capital, there's some transformative things happening that this group is very familiar with in the space of systems biology, systems medicine, certainly, you know, heart, lung, and blood space, reparative biology and medicine, regenerative medicine; capabilities to advance predictive help that might actually have us consider the preemption of chronic disease in the next couple of decades; the promise of addressing health inequities in a fundamental way that, again, spans basic translational clinical and population and community in an integrated fashion that we couldn't even consider before. And to take that not only locally, but globally, we have great opportunities to do that now, and clearly enabled by new tools. Again, this August [spelled phonetically] group knows more about omic technologies -- and I needn't say more -- but advances in imaging, informatics, computational biology, stem cells, nanotechnology. And also of note here, I'm emphasizing that the connectivity that the digital age brings us to create networks that cross disciplines in ways that I think will be transformative, that leverages this technology. And I think this is critical, again, in this particular moment of time. Again, our people's representatives are debating what's going to happen to Medicare costs in 2025 when baby boomers like myself are busting the budget. And this is shown on this slide. Certainly, one way is to think about making budget cuts to trim benefits and limit costs. But as a clinician/scientist, I have to be an optimist. I believe that the opportunity is to innovate in ways that, again, can start to bend this curve. And I would argue that the medicine that they'll be practicing in 2025 is related to the transformational advances we invest in right now. And that's really our task: to think about what we can do in discovery science and translational science that can bend this curve. That happened to be shown for chronic kidney disease, which is a major consumer of Medicare expenditures. But a lot of the other expenditures are also in the domain of heart and lung disease. So I think that really part of our charge is to inform this discussion and this debate with at least the possibilities that discovery science may have a role in bending the curve and making a difference. In that regard, I think understanding racial inequities gives us a special prism to try to understand how we might move forward to, again, bend these curves. These are things that this audience is familiar with. On the left is stroke mortality over the last 60-odd years. The noteworthy things are, again, we're making advances, but a persistent gap exists. The red and blue bars are African-American males and females, and that gap is persistent up to this day. Similarly, on the right-hand panel you see incident kidney disease. And the top group developing end-stage kidney failure are African Americans. So if we can sort of crack this nut and get at addressing these curves, I think this can be informative of how we can move forward together. And this prism, I think, is noteworthy because it emphasizes the fact that at the end of the day this is a multi-dimensional, complex, multi-level systems problem in a very fundamental way. Now, that could be so vexing that people give up. But the other hand is that this may be precisely the kind of problem that would take the kind of cross-disciplinary and use of tools that are currently at hand. Because it's quite clear when we look at those health inequities that it involves layers that are clearly biological and relate to genomic variation, but also individual in terms of behavior in the framework of a family, in the framework of a community, and within an environment. And, indeed, if we're going to make a difference, we have to think of it in that sort of way of complexity. Now, this is a very busy slide. But it attempts to try to describe this ecosystem that appears to predispose to these health inequities, and that appreciates those endpoints that I described before in stroke, and heart failure, and kidney failure; and a recognition, clinically, that that's driven by obesity, diabetes, or hypertension is particularly prevalent amongst African Americans that predisposes to these complications. But it also brings into play the notion of the environment, and in the era omics, that some are calling the "exposome." Those factors in the environment, the exposures in the environment that are influencing the predisposition to these risk factors: obesity, diabetes, and hypertension; and a recognition that social dynamics of racism and social deprivation set the stage for the development of a predisposition to these health inequities. Probably most pertinent to this group is this notion that we're describing as the biosocial interface, in which this group, in particular, is appreciative of that dynamic between environment and genomic variation that can influence disease; and a potential now for us to have the tools that we look at this interface. And we may argue that some of the initiatives of Genome Institute, as well as the Common Fund, are starting to look at this interface and how we can interrogate it by maybe understanding the microbiome, the immune system, the epigenome as something that might be responsive in a dynamic way to this environment, such that biological systems are altered to drive health inequities. At least this is a model to pursue. And it's one in which will go back and forth in this yin and yang between classical reductionist sorts of strategies, and more integrative, holistic, cross-disciplinary, systems-based approaches. And I think that's one of the exciting opportunities that lays before us. And again, I know that Genome is at the advance and vanguard in leading us through. I contextualized this challenge to -- by referring back to my former life and the study that we did when I was in Atlanta, in which we started with just a survey, a community-based survey of a biracial ambulatory population, middle-aged, in Atlanta, Georgia. And this is the sort of classic demographic profile that we got from this group. You can see they're middle-aged and, not surprising to you, the African Americans were more obese, had higher blood pressure, greater prevalence of hypertension, had more diabetes, and, of note, had less physical activity and lower diet of fruits and vegetables than whites. And the thought was that that may drive these health inequities and risks for cardiovascular disease. But what I find intriguing is what we're starting to learn about this, I think, is relevant to a lot of what this institute is about. I'm intrigued by the potential to leverage our cohorts and the exposome to get an understanding of how it's interfacing at the biosocial interface. And one of the provocative studies done by Christakis and her colleagues using the Framingham Database was to look at this phenomena of social contagion, in which they followed the Framingham longitudinal cohort and were able to track individuals who started off at about the same time, and tracked who became obese, and, basically, who didn't, and then mapped that to their social network, as shown in the top slide. And the bottom line is, that your BFF -- your best friend forever -- when you were younger, and both of you were lean, if your BFF became obese, you were more likely to become obese. And it wasn't just that birds of a feather flock together, if you will. There appeared to be a particular, again, social contagion related to that interaction and that affinity. And so one wonders, "Well, how would that be interpreted at a bio-social interface? What might mediate that?" And I think that's still speculative. But I guess I'm intrigued by animal-modeled data that exists related to the microbiome, and how the microbiome is modulated by dietary habits or what you choose to give your mice or rat, and the fact that that is transferrable between colonies. And, again, this group is aware that if you do a profile of the microbiome you can actually see signatures of the diet there and watch it change with intervention. And so I think this is one of those exciting areas of the biosocial interface that might be very helpful in helping us to understand some of these health inequities, and how the affiliations that come from segregation and other parts of interactions, and how that might, again, have a biological mediator at the end of the day. This was also noteworthy because when we'd studied these African Americans in Atlanta, one of the things that became quite clear is that the low physical activity amongst the African Americans was self-evident. But when we asked them the question, "Do you feel as though it's safe to jog or walk in your neighborhood?" disproportionately, the African Americans disagreed with that statement. They felt as though their physical activity was, indeed, influenced by their environment and the feeling that it was unsafe to actually pursue that kind of healthy lifestyle. And similarly, when we looked at where many of them were resided, here in the southwest quarter of Atlanta, and did an analysis of their access to healthy foods, we also recognized that there was a disproportionate concentration of restaurants that serve high-fat, high-calorie dense foods, and a relative paucity of supermarkets that provide fresh fruits and vegetables in that same neighborhood. So two of the key exposure variables may, in fact, be related to the environment people live in, and work in, and play in, as much as certain individual choices that they're making. And that, again, has biological implications. Some recent work this -- from a paper done by Wang et al that recognizes that the color that's part of fruits and vegetables has -- relates to chemical products of flavonoids that are broken down by the microbiome. And that the metabolites of those flavonoids then is able to modulate macrophage gene expression -- indeed, the expression of certain micro-RNAs -- that, indeed, then modulate the expression of transporters involved in lipid metabolism by the fully-macrophages that make up an atherosclerotic lesion. And they were able to -- Wang et al were able to show that manipulating either the metabolite or the microbiome could actually promote the regression of atherosclerosis. And so we're starting to see evidence of how these biosocial interfaces and, in this case, the microbiome may be playing a significant role in a way that might be explanatory of certain health inequities that we see. So I tried to just paint that picture of some emerging data that I think we find exciting about a path forward, one of which I know that this institute has already embarked on, it's already in the Common Fund, that I hope we can continue to build on. Let me sort of close out with this last example that, again, this body is very familiar with. That as we look at the social context and how it might interface with biological systems, clearly it's all interacting in the context of genomic variation and the population history that has shaped that genomic variation. And again, I don't need to spend much time on this slide from Carl Bustamante's work that shows that the mosaic nature of the genome, chromosome by chromosome, typically existed in most African Americans that spans different degrees and extents of admixture of European and African lineages, and how that genome has been shaped by centuries of exposures. This one giving just an illustration of Malaria, and how that has shaped the genome and actually variants that you see here that have been well described. And I'd like this paper as a paradigm, hopefully, of possibilities in the future. A paper by Genovese et al that I found very provocative, and included, actually, Dr. Kopp, who's here in the intramural program, in which they identified the association of the Trypanolytic ApoL1 variant in predisposing to chronic kidney disease, based on a mixture analysis of families with end-stage renal disease done by Friedman, Bowden, and others. And, characteristically, you can see the -- how the heterozygote sort of had an advantage here, in that the ApoL1 molecule would actually lice [spelled phonetically] the trypanosome that causes sleeping sickness. And so, clearly, this is something that was probably selected for and was advantageous in that contents -- context, and -- but now, in the context of high-salt diet in America, probably is not so good; and, certainly, in the context of hypertension, increased the risk five-fold. So one of the more robust -- actually, relatively common, if you will -- variants with a major effect on the end point of chronic kidney disease. And it may, in fact, be driving that curve that I showed you earlier as to African Americans having higher incident rate of renal failure. And that, to me, opens up a lot of exciting opportunities that I hope -- that I know, in fact, this institute's interested in pursuing moving forward in the next five to 10 years, in which this might serve as something of a paradigm in which we actually start to contemplate the use of markers, like ApoL1, to think about genomic medicine, therapeutic strategies, and/or as a discovery platform, if you will, for new therapies, new pathways, and pathogenic mechanisms of chronic kidney disease. One could imagine clearly playing a role in risk prediction, influencing therapeutic choices, the degree -- the lowering of the blood pressure, the strategy of lowering the blood pressure, and, as I say, identify novel pathways that will give us some insight as to what, indeed, promotes the progression of chronic kidney disease that seems so inexorable. So I'm excited, actually, by the opportunities to bend this curve, and to have an impact in which we might actually be transformative. And the drivers of Medicare expenditures moving forward, if we could, indeed, identify a risk population, develop a strategy that's actually preemptive in the development of this end-stage disease in a way that would be transformative to the patients, and actually -- may actually be transformative in terms of our economic imperatives. So I see a lot of opportunities for NHLBI and Genome to work in partnership. We share a common interest in the emergence of big data. And we're clearly committed to converting what is a storage problem into an opportunity to develop actual knowledge that actually drives medicine and public health impact. I'm always -- I always chuckle as a clinician -- you know, I still remember those days of, you know, going down to the medical record room, and waiting in a queue, and waiting for someone to disappear back into the stacks and bring you back a bunch of charts this full from, you know, Mary Sue in for her 12th admission. And so when I go on the Web, it's just remarkable how much we've lagged behind the digital revolution of the 21st century in biomedicine. And so when I go to Amazon.com, it says, "Hi, Gary." [laughter] And here's my actual screen shot. You guys are probably discerning and doing a psychological analysis of the books I read. But, suffice it to say, prior to Christmas, it, you know, suggested the new Jefferson biography, because I like biographies. And I actually did buy it based on that recommendation, and enjoyed it over Christmas. And yet it's all because they are tracing my behaviors, all my transactions, all my things. And they're able to develop algorithms to predict what I probably would buy for myself. And it just seems so incredibly humbling that medicine seems so far from what Amazon is doing. I also, like some of you in the room probably, would follow FiveThirtyEight and Nate Silver, and, you know, how he was able to take metadata and make so much inference out of it, and be pretty close to predicting things pretty good. And so I'm hopeful that that's something that we can do in the context of our enterprise. And with that regard, I'm hoping that we can think about rebooting Framingham -- I say this with caution with Teri Manolio in the room -- that we think about Framingham 2.0. Indeed, actually during the time before Genome stole her away from NHLBI -- for which we'll never forgive Genome -- that Framingham was starting to move in that direction, and I think was amongst the early cohorts that adopted genomic analyses and technology. And I think we have an opportunity now in version 2.0 to even leverage that further. I'm hopeful that folks from this institute will give us some ideas, because I think it's still relatively untapped how much we're using the fact that it's been such a multigenerational study for over 50 years. And we had these platforms, we had the next-gen sequencing capabilities; we had deep phenotyping, literally, on hundreds of families. And I'm hopeful that we can exploit that in a much more strategic, and effective, and high-impact way than perhaps we have using some of the older sort of platforms. And I think it's quite amenable to that, but we'd love to talk to you about how we might work on that together. Similarly, we're expanding the notion of omics to include a variety of platforms that are already embedded within that, and which we hope to enrich, including iPS cells, et cetera. So I think that the opportunities are great to leverage one of the iconic legacies of the NHLBI. I'm hopeful that we can work with you toward this concept of a scientific commons, if you will, that taps into the collective intelligence of the whole community and leverages across a variety of disciplines by, again, making more data and multiple levels publicly available -- not just the DNA sequence, but at the various levels, all the way up through the phenotype and the expososome [spelled phonetically]. At least that's what we would envision in partnership with this institute, in a way that captures the diversity of our cohorts, but also starts to bring in our clinical colleagues; the fact that we have clinical trial networks and clinical research networks that also have these capabilities to extend beyond the community-based cohorts to expand our case ascertainment and, therefore, controls as well. We're hopeful that with this scientific commons we can, indeed, collectively create this open multi-dimensional omic data repositories that, again, is accessible to more scientists than just a close group of investigators that might have been a part of these original cohorts. And I'm very hopeful and, perhaps, overly optimistic about the future, but I was very intrigued by one of the meetings I went to when I first started on this Bench-to-Bassinette Working Group and network that we have in our Pediatric Cardiology Group that Gale Pearson and Jonathan Kaufman [spelled phonetically] had been leading, that has gotten together a series of investigators who are probing congenital heart disease as something where we might be able to, again, leverage clinical ascertainment, advances in imaging technology, and the application of omics to understand potentially the role of de novo mutations in certain pathways that might predispose to a defect; and understand that, not only at this clinical level, but that it may relate to other biological systems, mouse models, et cetera, with the use of iPS cells, and characterize advances in our understanding of congenital heart disease in a way that would be unprecedented. Just go past that. And finally, the other thing I think would be very exciting to work with this group on relates to genomic medicine as we alluded to. That they're a great opportunity to -- again, Genome has played a leadership role on. I know Teri's been in this space with Emerge, and genomic medicine, and clinical sequencing that I hope that we can build on in the context -- again, in a complementary way that extends what we're doing at Framingham and cohorts, but closer to the clinic and clinical phenotyping where we can, again, leverage that linkage between information that's already there in electronic records, but increasingly is having genomic information superimposed in repositories that are happening around the country. And already in our Cardiovascular Research Network in NHLBI, you know, we have millions of covered lives through the health plan systems that are already part of this network. So when you talk about big data and tracking of outcomes, I think this is an incredible platform that gives us enormous opportunity. And I'd love to be able to superimpose our CTSA network on this, and to pursue things more in this direction of genomic medicine. So what I've tried to indicate to you are some opportunities that I think are unprecedented, and at least I'm excited about, that we can work together on. And I've put out this challenge to our staff, and I probably was crazy enough to do it in my first invited plenary at the American Society of Hematology. I probably should have asked you, Eric, first, whether that was a good idea or not. But I showed this slide to this group of hematologists as a cardiologist, because one of the things that I encountered when I was in Atlanta is Atlanta has one of the biggest sickle-cell clinics in the country. And as an adult cardiologist, it had not been hit home to me the fact that so many of our kids with sickle-cell disease suffer strokes at a very early age. This nation was kind of rocked by what happened in Newtown, Connecticut with the murder of 6-year-old children. And I must admit, as tragic and as horrendous as that is, I think it's also tragic that we have African-American children with sickle-cell disease who are having strokes, literally on a weekly basis, who are 6 years old. We've made advances -- that's what's shown on this slide -- with a clinical trial that the NHLBI funded, in which transfusing blood made a difference. But it would seem to me ambitious but feasible goal to set for ourselves that we would think about a stroke-free generation of children with sickle-cell disease. And I say this to this audience because this was the paradigmatic molecular medicine disease. This was the disease where we figured out the mutation a long time ago, and yet 6-year-olds are having strokes. Again, I don't need to tell this audience, there are probably some opportunities we can pursue to figure this out. Some of those have already been made in the case of cystic fibrosis. I think the time is right to make that happen in sickle-cell disease, not only in this country, but around the globe. And I think that we have an unprecedented opportunity to do that with things we have in hand. And, with that, I appreciate your attention. [applause] Eric Green: I'm certain Gary is happy to answer questions that the council members may have. Bob? Robert Nussbaum: I had wanted to follow up on the comments you made about minority representation in the research workforce. There's been this ongoing debate, or discussion, about pipeline versus falling out of the pipeline. And I look now at things like the MARC Scholar Program that is funded, I guess, primarily by NIGMS, which seems to go down, perhaps, to the undergraduate level, but not below. And I'm wondering whether you would be interested in commenting on, first of all, what your view is of the pipeline issue, and second of all, how can we overcome this chasm between K through 12 education, and then the undergraduate and above it. It seems like it's two completely different worlds. Gary Gibbons: Yeah. It's a great point, great comment. And if this was a readily solvable problem, I think we would've solved it by now. It -- at the risk of sounding like someone downtown, you know, it probably is one of those all-of-the-above kind of challenges. I just saw an article in the New York Times this Sunday about a town in New Jersey in which they start at pre-school. And, you know, all of us have kids. We've been blessed that they've gone on. Well, we started very early to put them on these trajectories. So I agree with you. You probably can't start early enough. You could argue, given what we already know, a lot of it's even in utero for all we know. So you can't start early enough. So then I think we had a challenge as the working group to say, "Where is the best, most targeted strategic place for NIH to play a role?" Recognizing that, quite frankly, you know, there's a whole department of education, et cetera, and there's a lot of players that should be in this space. So that's where we had to make a judicious, strategic decision about where we could do the most from an NIH perspective. And we came down a little close to what you said. And that is, although there are challenges all the way through, that when you look at the incoming freshmen, even into college, the underrepresented groups are a still a pretty healthy number of those who at least intend to go toward the biological sciences, even those who make it through to that point. Then what we looked at was from undergraduate, converting a graduate BS to a Ph.D. That's where we saw a steep decline, and where there was a dramatic gap now in terms of those who made that conversion. And that kind of led us to say if we, again, don't have unlimited resources or unlimited leverage, what could we do? We tried to hit that conversion. One of the programs -- and, again, it's not sufficient -- but one of the programs relates to reducing one of the disincentives, which is the financial burden that comes from taking this track, particularly after you've built up the debt of college education. And, as having gotten three kids through, I have an immediate appreciation for how much that is. The days of working your way through college for a low-income person are rapidly disappearing, if not already gone. So the notion of putting in a scholarship and/or loan repayment option, to at least reduce that roadblock or hurdle, particularly targeted at these groups, in conjunction with what is already there, in terms of MARC and what have you, we thought could make a difference. And then the second one is the one I described, which is the mentorship; that is, to link those kids in. That if that drop off is not because -- we want to be sure it's not because they didn't have opportunities and they didn't get the best guidance. And that's, again, what we're going to need to focus around the table. Eric Green: Howard? Howard McLeod: I have an institute question for you. One of the things that we struggle with is where does NHGRI start and stop compared to the other institutes. And I know it's a continuum and there is no start and stop, but our advisory role is for one institute, but often our scope of interests and opportunity is across the spectrum. And as you're new and in one of the great partner institutes, I wonder if you could comment on how you see things playing together. Gary Gibbons: Well, probably because I am new and I'm coming from outside the NIH, I see the importance of the collaborative synergies that potentially can exist here. I think we're in a fiscal climate, where if there ever was a situation where each institute could go alone, that's rapidly disappearing. So I think the reality of the situation is when things are tight we really have to look for those collaborative synergies. Again, I can't speak for Eric, but I would hope that we can work collectively in platforms that I believe are, in essence, disease agnostic. You might've noticed, for example, that I actually gave you a kidney example. Howard McLeod: We did notice. [laughter] Gary Gibbons: There was -- it's probably the rebel in me that, you know, hypertension is in our portfolio; kidney disease is in Griff's portfolio. But we're having collaborative talks because, obviously, when it comes to patients, they don't care about these things. And when it comes to the science, this institute, probably more than any, is interested in platforms and scientific questions that are clearly so cross-cutting and yet fundamentally important for us. So I think that in terms of the resources that we talked about and the platforms, I see great opportunities for us to continue to collaborate. And, you know, Eric and I are, you know, been going back and forth on this. So -- Eric Green: Henry [spelled phonetically]? Gary Gibbons: I think they're ready for lunch. Eric Green: Okay. Gary Gibbons: Thank you. Eric Green: Well, thank you, Gary. Gary Gibbons: I appreciate it. Eric Green: To be continued. Rudy, do you want to -- do you have the marching orders? Rudy Pozzatti: The orders are to go upstairs one floor and seek food. And you can also -- aside from eating in the cafeteria, you may want to connect with some of the program directors of HG, go to their offices. There's a conference room on the fourth floor that has a large room and seating there, as well. Please be back at 1:15. Okay? We'll reconvene at that time. [end of transcript]

Program details

A Vagelos Scholar is required to complete 40 credit units (c.u.) in order to graduate within the program.[4] This requires a minimum of five c.u. per semester, though some choose to take more. Most students graduate with a major in biochemistry and then choose to either submatriculate to obtain their master's during their undergraduate years or obtain a dual major in another science.

A freshman in the Vagelos Program takes General Chemistry I and II, Calculus I or II, and Physics I and II (including lab). Students with AP credit may choose to not take General Chemistry and instead take Honors Chemistry or Organic Chemistry. During a Vagelos Scholar's first year, he or she will also be required to take the Vagelos Scholar's Seminar (CHEM 022) taught by Dr. Ponzy Lu, the program head.

Participation in a faculty research group, of which there are more than 600 located on campus, is required.[6] Participants are encouraged to find work in a biomedical field, though anything related to their studies is acceptable.

References

  1. ^ "About Roy Vagelos". www.sas.upenn.edu. Retrieved 2018-03-27. 
  2. ^ "Ponzy Lu's homepage". www.sas.upenn.edu. Retrieved 2018-03-27. 
  3. ^ "Requirements". www.sas.upenn.edu. Retrieved 2018-03-27. 
  4. ^ a b http://www.sas.upenn.edu/biochem/graduates.html
  5. ^ Anthony, Laura. "Vagelos programs: Intense science education, but it's not for everyone". Retrieved 2018-03-27. 
  6. ^ "Research Topics and Laboratories". www.sas.upenn.edu. Retrieved 2018-03-27. 

External links

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