 Hello, and thank you for joining us for today's Great Challenges Live event, sponsored by Robert Wood Johnson Foundation. My name is Dr. Eric Green, and I'm the director of the National Human Genome Research Institute of the National Institutes of Health. And today, I've convened a few of my genomics friends and colleagues to explore what is already possible and what is just over the horizon in the world of genomic medicine. Finally, to introduce my guests, Dr. Amy McGuire is professor of biomedical ethics and director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine. Dr. Carlos Bustamante is professor of genetics and biology at Stanford University's School of Medicine. Dr. Jim Evans is a professor of genetics and medicine at the University of North Carolina School of Medicine and director of the Clinical Adult and Cancer Genetic Services. And finally, Sharon Terry is the president and CEO of the Genetic Alliance, a patient advocacy organization here in Washington, D.C. Welcome, everyone, and thanks for joining us. By way of background, since the completion of the Human Genome Project in 2003, ten years ago, NHGRI has led numerous studies to understand the genetic and genomic differences among people and how these differences may increase the risk for disease and also understand how best to use genomic testing to customize an individual's medical treatment. Since then, the global dialogue around genomics has been vast and has led to many unanswered questions. So today, we hope to explore some of these questions and even agree on a few answers. We'll take questions from viewers and from social media, so just tag your questions with the hashtag Great Challenges, and we'll answer as many of them as we can. So let me start with the first one. I'm going to direct the first question actually to Jim Evans. So Jim, you know, I remember when I was a medical student and I graduated in 1987, I am convinced I never heard the word genomics once throughout medical school. And yet, shortly after I graduated medical school, the Human Genome Project began in 1990 and then ended in 2003, and I was involved in the Genome Project, and we certainly started talking about genomics being relevant to medicine throughout the project and even 10 years ago when the project ended. But it seems that in the intervening 10 years from the end of the Genome Project a decade ago to now, there's been a lot, there's been acceleration and thinking about how genomics is going to be relevant to medical care, but it seems like right now there's tremendous excitement that even wasn't there three, four years ago. So as a practitioner of genetics and as a physician, what's different now even than two or three years ago? Yeah, I think you're absolutely right. There's a palpable excitement now that didn't exist a few years ago. And it's not because we haven't known for a long time, really since the 1940s when Avery at all figured out that DNA was important, it's not that we didn't know that this was very important, it could be critical to understanding diseases, but what has changed is that we now have the technology to examine genomes in a way that was undreamt of, even just a few years ago, five or ten years ago, certainly ten years ago with science fiction really to think about routinely analyzing all of someone's genes, and it's now something we can do. So it's really a testament to the power of technology and how that can change, and I think we see that in the history of science really all through the ages. Look what the telescope did for astronomy when Galileo used it, it's really, we now have the ability and that's what's changed. So Sharon Terry from a patient perspective, you've seen all this play out over the last ten years, sort of what's your view, is the last couple of years in particular let it change in your perspective or in the individuals you deal with through the genetic alliance? Sure, sure. So it's been amazing that, you know, genetic alliance is twenty-seven years old and no one had heard of genetics twenty-seven years ago. So what we're really seeing now is that we don't have to explain to people what genetics is, and then when we come to genomic medicine, people have begun to hear in the ordinary manner in which they go about their lives various parts of genomic medicine like, for example, drug response. It isn't unusual to hear people talk about, well, I just may have a different makeup than someone else who isn't responding or is responding to pain relief or chemo. So the other thing that I'm noticing is that the kind of exciting technologies that Jim referred to for being able to sequence genomes are putting us in a circumstance whereby remarkable numbers of studies are being done that are generating incredible amounts of data and actually incredible insights about possible role of specific genomic variants with specific diseases, but our ability to generate that data is outpacing our ability to analyze that data. Now, Carlos Bustamante, I know you're thinking a lot about this. How are we going to successfully deal with this onslaught of new scientific data to help people like Jim Evans actually take this to the bedside of patients? Well, I think that's the question that is facing us today as computational biologists and as people interested in making sense of the human genome. As you yourself articulated, we may be interpreting human genomes for many years to come. And I think it's an incredibly exciting time. The confluence of what's happening in big data, the ability that we have now to be able to do this on Google Hangout didn't exist a couple of years ago either. So it's that ability to do very large scale computing very quickly and to analyze range of data that we're going to need in order to bring to bear the infrastructure to analyze large scale human genomes. And in many ways, when you talk to people who've worked in big data, they used to think of the Large Hadron Collider as big data and all of what physics is doing is big data. And there's a problem now that people are going to be walking around with 500 terabytes or a petabyte of data that is their genome sequenced many times over, over their lifetime, and all of the ways that we can think about monitoring. And it becomes a very large challenge. People, even the Googles of the world's eyes light up and say, wow, this is something we need to begin to think about. Carlos, you're thinking about this at Stanford and you're working, are going to increasingly be working with people like Jim Evans at University of North Carolina. Can you maybe say a few things about what that new collaboration is going to look at and what its purpose is? So I'd say that one of the most exciting projects, if not the most exciting project we're involved with is this ClinGen consortium that NHGRI has put together that brings together Baylor, Stanford, the group at UNC, Harvard and a whole host of additional collaborators to generate the country's clinically relevant genome variation database. And our goal is to catalog in a central place all of the information that we can from patient testing data that's coming from clinical testing services all the way through large-scale sequencing projects that are happening at our large-scale sequencing centers in order to make that data accessible in different ways. Accessible to computational biologists who want to compute on it. Accessible to people who run clinical labs so they can ask questions about how often when I see a genetic variant has this been seen by others and how are they classifying it to doctors who want to use this in practice and eventually even to patients who want to be able to get more information about particular variants and what they may mean. So Jim, so tell us from the perspective of the collaborator at University of North Carolina but also as a practicing physician what's this going to look like in the next few years? Yeah, I think that one can distill really the magnitude of the challenge. If you think about the meaning of variants in our genome. We all, if we were to sequence your genome and my genome or Carlos or Amy's, we each differ of course by about four million places in our genome and as little as one of those can cause significant disease. So the challenge and one of the things that this collaboration seeks to explore and figure out is how do we find though that subset of variants, right, as few as one or two variants in a list of four million that will actually make the difference for an individual between health and disease. So those are both the exciting things and the challenges that we face as we go forward. So let me bring Amy McGuire into this conversation because what we were just talking about were very much sort of the practical issues of making the transition from scientific discoveries to clinical practice, but the clinical practice aspect of it also brings in patience and that means it brings in society. And there's many, many ethical and societal issues that those of us have been involved in genomics a long time have been grappling with, have been pondering and people like Amy have been studying. So Amy, hearing this discussion what are the great challenges that you are now looking into from a research perspective? Yeah, so I think one of the really big challenges in the last couple of years as with any new technology really is at what point is the right time to introduce it into clinical practice. And that raises a lot of questions about what are the benefits, what are the harms and what's the impact. So what's the impact on the individual in terms of how are they going to respond to the information that they're getting, what potential social harms might come to them in terms of concerns about their privacy, concerns about people accessing this type of information about them, as well as impact on their health. So a lot of people think that genetic information in particular might be very useful for nudging people to engage in health care behaviors that they know they should be engaging in anyways. And it's an open question about whether that in fact will happen or not. Also impact on the health care system. So when you integrate new technologies into the practice of medicine, you have to ask sort of what is the impact going to be on the health care system? And is it cost effective? Is it effective, comparative to other technologies that we currently have existing? So we want to make sure that the technologies that are being used improve health and that they don't lead to unnecessary overutilization that just costs more money without providing benefit. So I would say. You wanted to add to that. Yes, so I think Amy's absolutely right. And when I think about what Carlos and Jim are describing, I think the other piece that we need to come up to speed on is, yes, things like Google Hangout can happen for us in other sectors, but not so much in biomedical research or in clinical practice. And the current system of resting everything on a simple informed consent that then doesn't seem to translate very well into actually encouraging those genomes and all that clinical information to be shared is a critical issue in trying to do bigger projects. And I like to think about how can we empower little data to become big data? And if we put the individual at the center, the participant, the owner of the genome and give that person the ability to make decisions about where that genome will be shared and how it will be shared, I think we do two things. We educate the public and we also give them deeper engagement that's more ethical and actually lead to more participation in clinical research. Jim Evans? Yeah, and I would amplify that by just pointing out that we don't always share the same values about the same information. In other words, there's information in some people's genome that some people want. For example, knowledge about a very high risk for a very serious but untreatable or unpreventable disease. Some people want such knowledge. Some people say, no, if there's nothing you can do about it, I really don't want that. So we have to figure out also how to navigate this issue where the same information can be seen in many, many different ways by different people. Carlos Bussamante? So I think the incredibly exciting opportunity from the perspective of analyzing the data is that anyone genome may not be interoperable on its own. We see a genetic variant in a particular gene. We may not be able to know what it means. But it's in the power of putting that information together across thousands, tens of thousands, even hundreds of thousands of samples, that we can begin to get insights into important patterns. And one of the perhaps most exciting results that's happened recently is a discovery of rare variants and their impact on a gene that has to do with LDL, your bad cholesterol. And in fact, individuals who carry mutations in that gene have naturally very low levels of your bad cholesterol. Now several different drug companies are developing drugs, targeting that gene specifically in the hopes that many of us would benefit from taking that drug, regardless of whether or not we have that particular genetic variant. So those insights the genetics gives us into basic biology that could accelerate the development of medicines for everybody is one of the incredibly exciting opportunities. But in order to realize that, we need to be able to compute on the data, bring it together, analyze it with additional information that may be in people's electronic health records. So we face many challenges. And these aren't just challenges for computational scientists to solve. In fact, many of them are regulatory and ethical issues as we're raising. So the one aspect I think that's important to keep in mind is, and you heard a little bit about that from Jim Evans, is the technology shift that's going on. And I do want to pause here because there's a real history to be talked about this week in particular, both with respect to sort of important history from the past, but also important milestone all around DNA sequencing. I would note that the method for sequencing DNA that was used by the Human Genome Project and was used to sequence the first human genome was a method called didoxychane termination sequencing, big geeky name. But it was developed by an individual named Fred Sanger. And it's sad to say that this week Fred Sanger passed away. And sort of the end of an era, this is an incredibly accomplished scientist who won two Nobel Prizes. He won a second Nobel Prize for developing this method for DNA sequencing. But in this very same week, earlier this week, the FDA cleared the first genome sequencer. Now has been cleared by the FDA for diagnostic purposes. And I think that is very much important for a lot of reasons. But the symbolism I think is immensely important from the point of view of the recognition that genome sequencing really is here. And that technology, as Jim Evans correctly said, is going to thrust things forward. But it also, I think, reflects the fact that the general public and patients and people who are interested are really starting to recognize that being able to get information about their own genome is quite possible. There's even companies that are available that allow you to get information about your genome. So Sharon Terry, can you describe a little bit about how that landscape has changed, in part, driven by these new technologies? Yeah, so that's been quite remarkable to see how those technologies have changed and the accessibility, in fact. So people in the rare disease realm certainly are experiencing the opportunity to have their genome sequenced in clinical settings, which is quite remarkable. We kind of accelerated to this point much more quickly than I suspected. And then individuals are now gathering genomes from a number of these companies. And in fact, other projects like the Personal Genome Project. And I'm trying to understand what those genomes mean. And again, I think we're going to need to find ways to respect the privacy, security, sharing, data access preferences of the public in order that we share those with the wide spectrum of kind of sensibilities that Jim talked about, understanding that different people want to understand different things, but also knowing that we need that data and the associated clinical information for anybody to make sense of it. And with this week in these developments, including the FDA, this also brings in important issues around regulation and the kind of responsibilities the FDA has. Amy McGuire, do you want to tell us some things about that? Yeah, so I think the development with the FDA this week has been very interesting, because for the industry as a whole, there's been a lot of sort of regulatory uncertainty over the last couple of years. In terms of, as these technologies develop, how are they going to be regulated? By which agency and what capacity? What sort of evidentiary standard is going to be needed in order for these technologies to be implemented in a clinical setting versus a research setting versus in a direct to consumer setting? And so I think the fact that the FDA is acting on this and has approved the first next generation sequencing technologies this past week is a really good sign for the industry that the regulation is starting to catch up with where we are with regard to the technology. Jim Evans, what are some of the implications from your perspective? Yeah, one of the things that I always like to work in when the public's involved and we're talking about science is that we do have to be patient. I think that your articulating the history involved is very instrumental, is very instructive. We've known how to sequence DNA for quite some time. We're much better at it now than we were a few years ago. But we've known how to sequence DNA for decades. And yet, as is the nature of scientific progress in general, it's stuttering. There are U-turns. There are blind alleys. And I think it's the only way forward. It's extraordinarily exciting. But I also think that we sometimes do a disservice if we try to give unrealistic or if we give unrealistic expectations. Sometimes there's quite a lag between our increased understanding of a disease and direct application. But what that doesn't mean is that we shouldn't seek that out better understanding because it really is the only way forward. So let's take an example, a sign that does get certainly talked about in this regard. And in fact, we have major research programs we're now starting in this area. With these technological capabilities now in hand, the notion of sequencing somebody's genome early in their life, maybe right when they're born, and having that information carry with them throughout their lifetime is not science fiction. This probably is potentially quite doable. But there's lots of questions about whether we should do this. Now we are in a circumstance where we, in countries like the United States, we screen all newborns for a handful of genetic diseases. But it's a small number compared to the total number of diseases for which we know how to screen or we know how to genetically test. But what does that future look like? And when you start asking questions like should every newborn born in America have their genome sequence, that raises a lot of practical questions. It raises a lot of ethical questions. And it raises a lot of debate. I can tell you that much. So Sharon, why don't we start with you? What are your thoughts on where we are on this? And then we'll get a little bit into the kind of research that's gonna be done. But Sharon, what do you think of this? Sure, so we do know that, for example, the panels that have been suggested, as you said, only include up to 64 conditions, depending on how you count them, but that the opportunity to screen for 2,500 or more, and even whole exomes and whole genomes is available now, and that there are companies who are preparing to make that available. I think some of the things we wanna think about are the burden to the public health system, because that's a public health place. The newborn screening system is a public health system. And right now it has some difficulty with long-term follow-up of the individuals, the babies that are screened and what they need. Those are treatable conditions. When we start to screen for 2,500 or more, we're screening for things that are not treatable, perhaps. Now, I would say that clinically treatable is not always the way to decide whether or not to give parents information. My own two children were diagnosed at age four and six with an untreatable condition. It's still untreatable, but we've been able to really contribute a lot to that field because we're part of the community. I'd also say that having those genomes, again brings us back to the question that Jim brought up and that is who wants to know what? So some parents might want to know something. Does the child want to know? Does it then remove some of the autonomy that the child might have when they turn 18? So it does bring up a whole host of ethical considerations. And I think we're probably not envisioning the system that will allow us to do this and that is some way to manage these databases so that this information is revealed when someone wants to know, when the clinician needs to know for the sake of the family and to be able to gatekeep it in such a way that is ethical, respects privacy and consent and also gives the clinician the tools he or she needs to actually do good genomic medicine. Carlos, do you want to add to this conversation? Yeah, so, I mean, one of the things that is incredibly exciting is not only that you might sequence somebody when they're born but in fact that you might use sequencing as monitoring and in the examples that it gets used today or where you sequence a patient who has cancer and then you also sequence the cancer tumor and you might, in fact, not only sequence one, you might sequence multiple tumors or you might go back and monitor the individual with a blood test to see if something's come back. So you could imagine that, and it's not total science fiction that we might be using sequencing as monitoring and as a way of integrating that information along with other potential biomarkers. So, not just at the time of birth, but in fact as a way of monitoring health altogether. And Amy McGuire, I know you've thought about this a lot. Yes, I have. So, but yeah, I think I do think that we're starting to see the introduction of these technologies in the newborn phase and even prenatally, actually. And I do think it raises a lot of issues with regard to doing it with newborns. I think that we need to rethink sort of our public health model that Sharon raised with regard to newborn screening and think about whether this fits in to the public health model or whether we're moving towards a different kind of model, maybe a personalized medicine model that is different and shouldn't be state supported or state mandated but still can be provided and provide benefit to families. I think one of the major ethical considerations that hasn't been mentioned yet is just how people respond to this genetic information. So, I hear a lot of concerns about sort of the social stigma that this might create for children if they get a whole bunch of information about their genetic susceptibility to disease later in life. And is that gonna impact sort of their relationship with their family, their social relationships? Is it gonna create what we might call vulnerable children that are treated differently and kept out of sports and limited in their life activities? And I think a lot of that concern is legitimate and deserves to be studied and considered carefully. But I also think a lot of it is related to sort of misunderstandings about the role that genetics and most of the genetic information that we can generate today actually tells us about somebody's future health or future state of disease. And so I think it really represents sort of a reductionist view of genetics to think that if you get this information, you should act on it in ways that might be socially harmful to children. So I think we need to be very careful about those things and think very seriously about them and study them in rigorous ways to make sure that the genetic information that we're providing to families is done in a responsible way. It's communicated over time as it's needed in a responsible way and that people are responding to it in a way that upholds ethical and moral standards. So I completely agree with you. It's one of the reasons why our institute launched a research program that just started really just, or just in the process of starting. So Jim Evans, you know a lot about that research program. What can you add to the kinds of things that are gonna need to be investigated and the kinds of things physicians are gonna face around this area? Yeah, well I think that one of the things we need to resist in clinical medicine and in public health is the idea that we should do something just because we can do it, right? One of the things of course you learn in practicing medicine and in medical school is that we usually wanna have some gold in mind when you pursue a test, that we can do people harm by doing unnecessary testing and not to mention the societal harm. So my own feeling is that genome sequencing and sequencing of many genes is an extraordinarily powerful but a complex tool. And in some ways it's like an MRI. When you go to the doctor, they don't just give an MRI on everybody who walks in. That would be kind of crazy. It would actually hurt people because of our inability to interpret many things and the fact that we interpret wrongly. And I see the evolution of genomics in medicine as similar. I think we will apply it hopefully when and where it can really help us diagnose people, where it can really help us identify those who are at risk when we can do something meaningful about that. And I think that we do need to keep in mind the difference between clinical medicine where we're very goal directed. We're trying to improve health and research where we are driven by curiosity and that's completely appropriate. So I'm all for sequencing lots and lots of people but I think we need to keep separate the context of doing that, driven just by curiosity and hope for the future in research and by doing it in patients who have a very discreet goal. They want to be better, not have a bunch of possibly irrelevant and even misleading information generated. So let me bring our audience in because we've been getting some questions from the audience and as I half expected, we got some questions about some of this, what's known as direct to consumer genetic testing issues. So Stacey from Twitter or via Twitter asked the following, what if patients contributed to the conversation via home DNA reading kits such as 23andMe? And maybe I'm gonna ask Sharon in a second to take that question for starters but also the second part of the question is how are clinicians reacting to increase patient knowledge? And at a minimum I wanna go to Jim on that but I'm happy to have others weigh in as well. So let's start with Sharon. Yeah, so we're actually testing an idea and then looking at it as a research project to see what would happen if individuals did contribute their own genomic information. Again, with clinical information because as Amy said and others have said it is not valuable just to make decisions based on the genome alone. And that is becoming more and more possible because of a lot of technology, certainly the acceleration of the decreasing cost of sequencing but also because of other kinds of technologies to help manage that information and to bring in other kinds of providers not just physicians or genetic counselors but to bring in other clinicians that would be helpful to the individual as they go forward with that. I think we need to encourage the public to become more involved in biomedical research in general and this might be a way for us to see where everyone can contribute something. You don't have to have a disease or be in a specific situation. Everyone has a genome and can contribute it but again I wanna make sure that we do that in a reasonable ethical, safe and cost-effective way. No question but we also wanna think about research opportunities here. Carlos Pustamante, you wanna make a comment about that? Yeah, so one of the things that has been seen from the direct to consumer companies can do is by aggregating large amounts of data they can actually do studies themselves. 23andMe has actually published some really cool studies where they've been able to replicate finding from large scale genome wide association studies based on surveys that they've done on their customers. Now, there's a whole ethical issue of what people are getting into when they sign up for these direct to consumer companies but in theory, that model of what I would call inverting epidemiology or even the creative destruction of epidemiology where you have people self enroll is incredibly powerful. If you wanted to create a system to follow 100 million people you could take all the federal budget and you still wouldn't have enough money to do it, right? But you could imagine an opportunity for public-private partnerships where this could be done very cost-effectively and data could be gathered in ways that would be really beneficial to everybody so that we could begin to analyze it together. Jim Evans, what's your take on this area? Yeah, I have been a fairly vocal critic of the DTC genetic community. I think that there is real potential and I certainly want people to be able to have access to their genomes if possible. I think on the research front there is potential there and we need to investigate it. I think it is by no means a foregone conclusion that massive amounts of uncurated data that are self-reported will necessarily lead to tremendous and qualitatively new insights but I think it's definitely worth studying. Excuse me, as a physician, I am all for an informed patient. The thing that I think we have to remember though is that when I want to decide what kind of car to buy, I don't go to Toyota and ask them to inform me because I know pretty much what they're gonna say. So I do think we have to remember that the DTC genetics community has other motives, not just the motive of the individual's health and therefore I think we need to make sure that people are well informed and informed and impartial ways. I don't think that basically marketing is the best way to roll out complex medical tests. Amy McGuire, do you want to make some comments here? Sure, yeah. I think that when you're talking about direct to consumer genetic testing, we need to remember and this ties into what Jim was saying that we're really shifting from a physician-patient relationship where there are a lot of implicit expectations about the physician will provide information that will potentially benefit the patient that's in their interest. Their primary responsibility as a physician and their role as a physician is to benefit the patient and do what they can to help the patient. And I agree that the direct to consumer setting is a very different model. It's a consumer model in a market economy and so people who are going into that and are purchasing those kits, I think it's wonderful if they want that information but I do think they need to be aware that they are now responsible for the information themselves as a consumer and so they need to make sure that they know what they're getting into, that they've read the privacy policies of these companies to know what their privacy rights are, that they understand the kinds of information that they'll be getting back and the limitations on what that information can tell them about their health and about different traits and that they fully understand that their information will be used for research purposes and that they agree to that because in these companies a lot of times when you sign up for the product it asks you to also agree to have your data put into a research database and so for those people who are comfortable with that that's a fantastic thing but I wonder if there are some people who are doing that who are not quite aware that that's what's being done with their data. So let's change topics a little, go to another area that often gets discussed around genomics on an area of great interest to many including I know all on this panel today and that relates to health disparities. So there are so many examples of human diseases that clearly the effectiveness of treating patients or this particular diseases and the severity of those diseases vary considerably among different communities and different populations of individuals and there has been discussion that maybe genomics would help illuminate what the genomic basis for those disparities are, that's almost a research question but at the same time there's been some concerns that genomics being very technology oriented and especially early on might end up being expensive or might end up only being available to certain segments of society who have the access to cutting edge medicine might actually exacerbate health disparity problems we have in this country and elsewhere. Maybe we can start with Carlos Bustamante. You know, how can genomics as a research tool teach us about some of the genomic basis for health disparities? Well, thanks Eric. That's a topic that's near and dear to my heart. So one of the biggest concerns that many of us have is that the vast majority of genetic studies so far have largely included populations of European descent. There are now some projects underway including some of the ones at NHGRI that we're involved with like PAGE that's broadening ethnic representation and that's a critically important question understanding when a genetic variance is associated with a particular phenotype, how often is that association seen across populations? But there's also the issue of opportunities that one gains into basic biology of disease by looking at different populations because different populations may have accumulated different sets of variants in different kinds of genes and they may give us different insights into networks of that are involved in disease. But I'd say the biggest concern is that whenever you introduce a new technology you're gonna create a tier of concierge medicine say where there are people who can afford to go and have their genome sequenced and the tumor sequenced weekly and they'll have much better management and care than individuals who won't. And I think we're all in the same boat that we wanna prevent that from happening. The other view is that of course genomics is giving us insights into basic biology and that's helping us develop new drugs and therapies that'll benefit everybody. So I think it's a complicated issue but broadening representation is something that across the board is gonna help us in addressing those concerns. But tough issues to face Sharon Terry what are your thoughts about this? So I think this is a great place for us to actually reduce disparities and I think it's gonna be hard to but we need to actually shift how we think about engaging people in genomic research or any research and often as a consumer, as a mom coming to various projects I was given a seat at the table and I was supposed to be pretty happy about that. In fact I think we need to start to invite those very communities to decide where the table will be what are we going to eat, who's gonna come to the dinner and involve them as participants in the research again really engaging them deeply. And I know NHGRI has done some great things with its LC program and community engagement and disparities. We need to take that and make it much broader, much bigger and really ask those communities what do they need and how do we get to what they need. Amy McGuire you wanna add something? Yeah I mean I couldn't agree more with Sharon with regard to getting individuals and a broad variety and diversity of individuals involved in setting the research agenda, talking, participating in the research. From a clinical perspective in terms of access I think one of the biggest issues for a large number of Americans is going to be a reimbursement uncertainty and uncertainty around reimbursement. So I think right now when you are, we're just starting to try to figure out when you're ordering a genomic test clinically whether insurance companies are going to pay for that test or not. And really what insurance companies look for is whether there's clinical utility and because it takes a very long time to generate data on clinical utility I think we're gonna have sort of a period of time where we're gonna be in transition and there's gonna be a lot of questions. It also requires other complicated considerations like what codes do you use to try to get reimbursed for different tests. And so I think that's a huge major issue that's starting to be tackled and of course doesn't address the even larger issue of all of the uninsured and underinsured Americans and whether they're gonna have access to these types of services when and if we can show that they are clinically useful and beneficial for particular purposes. Jim Evans, what do you think about this? I was a practicing physician. I mean how much of the kinds of disparities that we see do you think we will eventually get at and underline genetic basis and versus other factors and how optimistic are you in this area? Well I think that this is a problem that as Carlos said goes well beyond genomics. I think we do run the risk of exacerbating disparities anytime we introduce a new technology. That isn't a reason to not pursue that technology. What it is however is a compelling motivation to try to correct those disparities. There's nothing more heartbreaking than sitting with a patient who needs something that they can't afford because they don't have insurance or they don't have good enough insurance, et cetera. I think that I don't see genomics as uniquely creating disparities nor do I see it as the key to eliminating them. I do think that the Genome Project and the NHGRI really set a tremendous example early on in the history of that project in earmarking funds, a specific percentage of funding that would go towards looking at just these types of issues, trying to mitigate them, trying to resolve them. And my hope is that the kinds of progress that are being made in the genomics community and we have many projects that are addressing these subjects head on, will be embraced by other institutes, other research because in the end it isn't good enough just to find effective medical diagnostic tools and treatments. We need to figure out how to apply those to everybody when they work. So let me shift gears, we have a little bit of time here and I see some questions have come in from members of our audience, interrelated ones that are not directly relevant to medical care and genomic medicine per se, but certainly fit in the general area of interest by the general public that brings them to genomics and gets them interested in genomics. Some of this relates to human history and ancestry and something about human origins because the genome is something that connects us to our ancestors and powerful new technologies that have allowed us to sequence humans today also allowing us to trace some of our history by sequencing samples from the past. So Carlos Bustamante is sort of one of the experts in this area, what can we learn about our ancestors, about our evolution through genomics? Well, this is one of the places where genomics has just been completely revolutionary. It has really transformed our understanding of the great human diasporas and how those events occurred and when they occurred. Just yesterday, there's a fascinating paper published on a 24,000 year old Siberian boy that was sequenced by Eskia Vylershev in Denmark and what they found is that this individual is actually telling us about an ancient population that was an ancestor to both Native Americans and present day Europeans. And so it's a very fascinating opportunity to gain insights into these events that have left no written record in the, and have been in some sense lost through the sands of time, we can now reclaim them. The sequence of the Neanderthal, for example, has led insights into a potential admixture between humans and our closely related sister species. So it's incredibly fascinating opportunity that we're now gaining and we feel extraordinarily lucky as a generation of population genocists to be the ones that are able to see this. The other thing that's happening is opportunities in this technology spilling over into agriculture into conservation. We're now sequencing many, many endangered species. We're beginning to use that information to design management programs. So it's an incredibly exciting time to be in the field and for any students who are out there or considering a career in genomics, aside from the incredibly important applications in medical genomics, it's just really an incredibly transformative science that is really upending many of long established practices. So I encourage you to consider a career. And Carlos, do you agree with me that stories like you just gave are also helping to raise what I would call genomic literacy, the general public's knowledge of genomics, and therefore that also might help them understand it when it gets to be something relevant in the clinical setting? Absolutely. I mean, I think if you talk to 23andMe, for example, they say that people get involved with their service because of the ancestry testing, but they stay on because they're interested in the results that they might be learning about health. And for us, it's just been incredible to see the actually public sophistication that when you give talks and people from the general public have an incredible ability to make sense of particularly the genetic history components and how we can use this, for example, to understand the transatlantic slave trade, one of the topics that through the barbarism of the transatlantic slave trade, we've lost a huge amount of the history and information and African-Americans and African descent populations in the US are very interested in trying to reclaim that history. And genetics is providing incredible insights there. So it's an incredibly important tool. We have to do it right. I mean, I think one of the things that we all agree on is that we can't be overselling the science and promising people things that the data aren't telling us, but with our ability to do finer and finer scale analyses, we are able to look and peer further and further back in time. So it's incredibly exciting opportunities. But attaining true genomic literacy is not gonna be easy, Sharon Terry, is it? No, it's not. We know that because we have seen the public succumb to some of the hype and then be very frustrated and worried. We also know that science literacy in general in the US and elsewhere is low. And so layer on top of that, something like genetics, but I very much agree with Carlos that these kind of more human interests, where did I come from, who am I? Kinds of inquiries really help us to start to understand why genetics might be important. Jim Evans, what about medical schools and what about medical education and postgraduate medical education? Are you seeing a change in recent years? And then similarly, what are you seeing with the patients? Are they coming in more knowledgeable about genomics? Very much so on both ends. Just as you said at the outset of this, when you and I were in medical school, nobody really talked about genes and it wasn't because we didn't know they're important. Again, it was because we didn't know what to do with that information. We didn't know how to obtain it, so there wasn't a lot of point in teaching about it. Most medical school curriculums now involve a significant component of genetics. In fact, we have it enmeshed into the very first block of courses that our medical students take. I think the other thing that we see is on the public's end, we see tremendous increase in knowledge about genetics and an interest. We're all somewhat narcissistic and there's nothing more gratifying in some ways than looking at our own genome and are looking at our own genes. We have a natural and understandable interest in that. So our patients are intrigued by that. I think that if you look at, for example, the recent new exhibit at the Natural History Museum in the Smithsonian, on the Mall in Washington, DC, there've already been over a million visitors to that exhibit, which opened just in June, that the NHGRI was critical to in putting on. So patients are interested, medical students are interested, and we're finding ways, we hope, to also educate practicing physicians because we forget most of what we learn in medical school and we need to be retaught that. But of course, the more informed people are, the more they can become engaged in some of the ethical debates and dilemmas that all of this brings about. Amy McGuire, what are your thoughts about the importance of genomic literacy for the kind of work that you do? Yeah, I think it's hugely important for people to understand the information that's being generated, particularly if they're going to engage in genetic testing. And I think it's important when we think about some of the ethical issues, when we think about the science, I mean, people should understand only the genetics, but they should also understand and be sensitive to some of the ethical issues that are out there. And so I think we have also this interesting, competing sort of tension right now where we are with regard to genomics because as people start to understand it more and they start to think about some of the ethical issues, on the one hand, we have a lot of concerns about sort of this information says a lot about me and it says a lot about my family members and I think there's an increased sensitivity to issues around privacy. And those concerns about privacy are really very historically rooted in sort of the early 1920s and 1930s and the social politics of the United States even before the politics in Germany around eugenics and the social meaning and treatment of genetic information which at the time was just really, we didn't know what genetics was, it was really about inheritance. So we have sort of that on the one side and then the other side, I think we have sort of this culture now of people sharing more information openly, they understand the information, they wanna network with other people who have similar information, there's a lot of social networking around genomics right now. And so I think we have sort of those two tensions and as we gain more familiarity and sort of comfort with genomics, I think we're gonna see those continually at play. So all of you allude to things that are new or that are being tried whether it's an exhibition at the Smithsonian or social networks and social media, but I'm gonna ask Jim Evans because a specific question and that is that there's sort of a teachable moment when patients are diagnosed with the disease, especially one that we know something about the genomics. As a practicing physician who has to sometimes tell patients about their disease and they wanna immediately learn more about the genomic basis for it if there is some known, what's missing right now? What do you wish existed that would help you with that patient-physician interface? Yeah, I think that one of the things that is interesting are some of the attempts to make genetic information more accessible through the webinar to individuals. But to be honest with you, I think the one thing, the biggest thing lacking as we sit with patients and try to explain that is our own understanding. We are in the absolute infancy of our understanding of the genome and I think it's very important that patients understand when we know things and they understand when we are unsure and don't know things. So what we really need, I think, are not necessarily new techniques for educating, et cetera, although those are welcome. What we need is just more knowledge and that is hard-bought and it's difficult to come by and there's no substitute for just slogging through it in research. So I think that's very helpful. I wanna take, we're gonna take one more question from Twitter and then we're gonna have to start winding down. But there's a Twitter question, I'm gonna put this to Amy McGuire who said, is there anything being done to protect the privacy of people in regions where there is no genetic test related law? So Amy, the issue really relates to sort of privacy and maybe things that slip between the cracks of current protections. Yeah, I mean I think one of the big challenges we have with regard to privacy protection is that there really is no comprehensive laws out there that protect privacy in this area. So we have a couple of, we're sort of in a better position than we were several years ago where we have a couple of federal laws that provide some strong protections. We now have the Genetic Information Non-Discrimination Act and that addresses and prohibits health insurers and employers from using genetic information in discriminatory ways. We also have sort of ways to limit access to particular protected health information including genetic information now, which is the Health Insurance Portability and Accountability Act, but there really is no comprehensive sort of regulation or law that protects privacy and there's also very few laws and regulations that address what happens when somebody inappropriately accesses genetic information and uses it in harmful ways against people. And so I think actually in that realm the United States is a little bit behind sort of some of Europe and other areas where they've addressed this through criminal laws and things like that and we really don't have anything like that in the United States. Sharon Terry, do you wanna add anything to your perspective on this? Sure, so having been very involved in getting, excuse me, the Genetic Information Non-Discrimination Act passed, I agree with Amy very much and I think in places where there are no protections we need to also start to evolve better social models that don't rely just on law and regulation but in fact on us as a society to respect the differences between individuals and the commonality so that we're not just placing our trust in regulatory systems. So as I expected, this was gonna be a terrific conversation with the four of you but we're gonna start to wind down and so I'm gonna ask a final question for all of you so everybody's gonna get a chance to answer this. So through the Great Challenges program is focused sort of on issues that can't be solved with a simple cure. We can certainly identify smaller, less magical steps that might make a significant impact in this space. So with so many critical issues driving complexity around this topic of genomics and genomic medicine, where are some of the best places to start focusing our attention? In other words, what are some of the things we can do to see an improvement in the short term in order to build momentum and to gain hope in the future? So let's start with Jim Evans since I asked him the first question originally. Yeah, I think that one of the ideas that I'm very excited about is that about depending on exactly how you define it, about half to 1% of people out there walking around have a mutation that predisposes them to quite a severe disease but one that is very preventable. Now it's not most people. In fact, 99% of people I don't think that applies to but we now have the ability to find individuals who have genetic changes that predispose to very severe but again, importantly preventable disease. And I think that that's something that we will begin to use. We could begin to use that with appropriate study and investigation in the short term and I'm very excited about the potential to use genomics in that targeted directed sense to really improve health and I think we will see that happening. Amy McGuire, what's your thought about this? Well, I think right now one of the most exciting areas where this is being used really effectively is for those families that have been on very, very long diagnostic odysseys where they have an undiagnosed genetic condition and they've spent years getting testing done trying to figure out what's wrong and usually it's with their child because usually this is in pediatric populations and we're really seeing tremendous advances being made in the use of this new technology and helping to those families to get a diagnostic answer to find out sort of what the reason is that their child has been sick all these years and we're starting to see some isolated cases where you can actually go beyond that and find influence treatment and say not only do we now know what's wrong with your child but that leads us to sort of treating them differently and that can improve their health but for most of those cases it's really just having the information that really ends sort of this very long diagnostic odyssey that can be very painful and difficult for families. Carlos, Boussin, Monte? So for me, I think the most exciting opportunities are happening at the interface of computation and genomics and the idea that we can begin to sequence largely particularly saying cancer and really make informed therapy decisions as to what agent and individual should get based on the actual tumor that they have or that we can begin to gain insights into the networks that underlie a cholesterol transport for example, in short circuit the long road that it takes to get new drugs to market I think is incredibly important and in order for that to happen we have to share genetic data and coming up with the regulatory mechanisms to make that happen is one step but we can begin by building the algorithms and infrastructure to make that happen and for me that's the most exciting challenge we have ahead. And Sharon, Teri, your turn. So I think for me, and I certainly agree with all of these as great steps is really participant engagement and looking at how do we basically get people to reclaim their health? We own it, we should use it, we need it and we sometimes abdicate to others and so I think genomics might be a great place to start to get that deep engagement that allows other individuals who have been on the diagnostic odyssey for a long time to participate but also has the general public stepping up and being part of the process. So one thing I can say, I find gratifying about your answers is I can assure you every one of the things that you just mentioned in each of your answers are things we're critically thinking about and actually in most cases very much engaged in at the National Human Genome Research Institute and I can really tell you that there's considerable excitement around all the areas that you're pointing out and we're very committed to really see them reach fruition. So these are all great ideas and I hate to say it but it looks like our time is essentially up. So please don't hesitate to share your ideas or ask questions we didn't have time to get to today. We'll connect offline and answer as many as we can. And now for some news from Ted Med that I know some of you are anxious to hear, right? That is now Ted Med is launching the application and nominations process for the Hive at Ted Med 2014. Now last year the Hive featured 50 entrepreneurs and their ideas, products and tech creations to enhance health and medicine in the pursuit of what's next in healthcare. So good luck to all the applicants for this new endeavor and thank you everybody in Ted Med community and our guests for today. So goodbye everyone. Bye, thanks.