 We're now going to hear from Amy McGuire from the Baylor College of Medicine. Amy is going to be talking about ethical, legal, and social issues in genomics reflecting back and planning ahead. And thank you very much for inviting me to be here today. It's really exciting to be part of this celebratory event, and I'm very happy to be here. So I was asked today to talk about the ethical, legal, and social issues in genomics. And study of the ethical, legal, and social implications of genomics in the Human Genome Project has really been tightly integrated with the entire NHGRI and the Human Genome Project since its inception. And so the ELSI program in the Division of Extramural Research at NHGRI was established in 1990, and it has always been structured as with a multidisciplinary focus. Its original function and purpose was to identify and examine key ethical, legal, and social issues associated with mapping the human genome, to stimulate public discussion about the Human Genome Project, to develop policy options, and to expand public education. And as the NHGRI has moved beyond the Human Genome Project, so has the ELSI program, and so it is still dedicated to these four kind of missions, but now related to the broader issues in genomics. The ELSI program at NHGRI has organized their funding of extramural research around four general topical areas. The first is privacy and confidentiality and the fair use of genetic information, including genetic discrimination. The clinical integration and impact of genetic testing. Issues related to genetic research, including things like research design, and issues around informed consent and human subjects research protection. And education and the development of resources to stimulate public education around genetics and the ethical, legal, and social issues associated with genomics. And so there has been a tremendous amount of success within the ELSI program and the research that's been funded by the ELSI program and all four of these areas of research over the years. And many of my colleagues who have sort of set the groundwork for the research that we're doing today have been successful at engaging with the scientific community and conducting research that's been useful and impactful on science practice and policy. And I'm not going to really go into any great detail about sort of the projects that have come before us, but I want to point out that one of the most, I think, impactful things that the ELSI program has done is really to sort of lay out a new area of research. And ELSI's really come to represent and it's kind of a representation of a broader area of research that deals with ethical, legal, and social issues in science more generally that takes a multidisciplinary approach. And so this has been accepted at an international level and I think that the importance of studying these issues in all areas of science has really gained a lot of traction and I think that can be really traced back to the beginning of the ELSI program at NHGRI and NHGRI's dedication to looking at those issues in the context of the Human Genome Project. So I'm going to talk about this broader ELSI research area when I talk about how we can plan for the future and some of the things that we might be thinking about in conducting the research as we move forward in plotting our course over the next 10 years. So if we look at the strategic plan that we've been looking at all day, there's a text box that's dedicated to identifying some of the salient and critical ethical, legal, and social issues that are going to be implicated over the next decade and these are organized into four major categories, ethical, legal, and social issues related to genomics research. Things like human subjects research protections, ensuring that we have diversity in our cohorts and our research cohorts, making sure that we have effective community engagement and getting the community involved in our research project. There are a lot of issues in the area of genomic medicine as we see this translation into genomic medicine. I think some of the most important ones are making sure that we are effectively communicating with patients about the uncertainty and evolving nature of predictions based on genetic information and also effectively evaluating the effectiveness of genomic services as they get integrated into clinical care. There are legal and policy issues that I am particularly interested in and I think the strategic plan really highlights three of the most important ones which are issues around intellectual property, issues around insurance reimbursement for genomic services, and issues around the regulation of genetic tests. And finally there are broader societal issues that are largely conceptual in nature that have to do with implications of how genomic knowledge changes how we think about human health and disease, how we think about self-identity, how we think about things like free will and individual responsibility. So all four of these areas are extremely important and there is very good research going on in each of these areas. And what I am going to do today is not talk specifically about the research topics themselves, but rather to try to identify a couple of major themes that can help shape the ways in which we do the research that can make it most impactful as we move forward in the area of genomics. And so in 2008 there was an assessment panel that looked at the LC program at NHGRI and they published a report and kind of strewn throughout that report are three major themes that I think come up for charting the course for the future of LC research more broadly. I think these three themes are also integrated in some ways into the strategic plan that was published yesterday as we look forward to how this area of research will progress. So I'm going to talk about each of these three integration, collaboration and expansion and I'm going to use my own experience and my own research to try to illuminate each of these domains or each of these themes. So it's a rather narrow lens through which we'll be looking at these themes. I'm going to recognize that there's a lot of research going on that can help inform how we think about these three domains. But I want to use my experience to try to show you my perspective on how these things have come into play in my research. So with integration, here I think that the main idea is that there's been a tension in sort of LC research since its beginning between LC researchers being responsive to the issues that are coming up for scientists as they're coming up and helping them to manage those issues in real time versus LC researchers trying to identify the larger, broader issues that might be implicated in different areas of genomics and to study those broader issues, slightly detached from the research that's going on at the time. And I think that this tension is very healthy and both kinds of research are very important for the LC field to advance effectively. But my personal research has been more focused on the first model. I've been very informed in the kind of research that I do by the scientists that are doing the research and the issues that are coming up for them in real time. And this is just one example of several that I could tell you about. So in 2007, Jim Watson was up here earlier and was telling you about getting his personal genome sequenced. He mentioned that his sequence was done by 4.5.4 Life Sciences and it was analyzed at Baylor College of Medicine. And I can say that since, in that project, the scientists both at 4.5.4 Life Sciences and Baylor College of Medicine were very conscious and conscientious about the ethical, legal, and social issues that were going to come up in the context of that project and the broader implications that that project would have for sort of how we integrate whole genome sequencing into our research practice and clinical care. And so as soon as Baylor College of Medicine got involved in this project, I was brought on board by our Genome Sequencing Center and Richard Gibbs and was intimately involved in the entire project. I went to all of the scientific meetings and participated in the planning of the project, helped them identify the ethical, legal, and social issues that were coming up and to manage those the best that we could. And even participated as we started to disseminate the results of the project through different press releases and publications. And you can see here we had a paper in Nature that was a letter, that was a four-page letter, kind of describing our results. An entire page of that was dedicated to identifying the ethical, legal, and social issues were in the project and providing a justification for our management plan in the context of this particular project. So I think that's a good illustration of how we had a very close integration between the science and the LC research and how they both sort of served to foster the other and it really resulted in, I would say, better research on both sides. This project got me really interested in some of the issues that I worked with some of my colleagues in the LC community, Tim Caulfield and Mildred Cho, and we thought about the issues that had come up in the context of this research and thought more broadly about the policy implications of that when you have research participants who aren't Jim Watson, because, frankly, some of the ways in which we managed the project were specific to the fact that we had a very unique individual before us who was the research participant. And so we thought about these issues a bit more broadly and wrote about them and put out some preliminary recommendations for managing them and research with other research participants' involvement. And this also led to an international consensus working group where we got a bunch of people together and we talked about these issues and we went back and forth and we looked at some analysis and looked at data and we came up with a more solidified set of recommendations that was published in PLOS Biology. This project also got me and a couple of my colleagues really thinking for the first time about how are we going to manage, what are going to be some of the ethical, legal and social implications as we start to integrate this technology, this whole genome sequencing into clinical care. And so we thought about those issues and wrote about them kind of trying to tease out what would be the health system challenges and implications of routine integration of whole genome sequencing and that's work that I continue to think about and continue to work on. So that's an example of how we... one example of how LC research and the genome science has kind of integrated itself in a way that I think was fairly successful and again, there are other models that are out there as well. The second theme that I want to talk about is collaboration. This...from the LC research perspective, I think we are and should be interested in ethics and legal and social issues associated with this research. And to me, I really feel strongly that if you don't combine sort of a multidisciplinary approach and consider all of these various facets of a given topic, then you won't have a clear picture of what you're thinking about. So let me give you an example of this. I've been in some research around direct-to-consumer genetic testing. So when some of these companies like 23andMe, which you can see the 23andMe spit kit here, which was named Invention of the Year a couple of years ago, when these technologies first came out and these companies first started advertising their services, I think it was in 2007, I became very interested from a variety of different perspectives. And early on in sort of the life of these companies, there was some pushback by a couple states, New York and California. They sent letters to a couple of the companies and they raised questions about whether providing these services was somehow in violation of their state laws and one of the laws that they were particularly interested in was the law that most states have that prohibits the unlicensed practice of medicine. And so from a legal perspective, I was very interested in whether this type of service constitutes the unlicensed practice of medicine according to state laws. And so I partnered with a legal colleague of mine, Cindy Marietta, and we did an analysis of state laws on the unlicensed practice of medicine. And what we found was that there is really not very good, clear guidance, which sometimes you do find. And that most states do have laws that prohibit the unlicensed practice of medicine, but whether this is the practice of medicine really turns on whether you consider giving somebody predictive genetic information to be a diagnosis. And there's not very clear guidance, there's a lot of opinions, but not very clear guidance on whether that is diagnostic. So it occurred to me that how consumers perceive this information may become very relevant from a legal perspective of whether it's diagnostic information. So if the consumers are perceiving it to be diagnostic information, that could become relevant in a court of law if this ever gets challenged. And so we decided to look at this from an empirical perspective, and we did a very, very pilot study. It was a cheap, unfunded, quick study to kind of get our finger on the pulse of what people thought about this and a couple of the other issues associated with this emerging industry. We've hosted an American Journal of Bioethics, and what we did was an online survey and we used Facebook.com users, and this was done in 2008. And the reason we chose Facebook.com users is because some of these companies engage in social networking, and we thought that perhaps users of Facebook.com may be some of the early adapters of these companies. So we surveyed just over about a thousand individuals, and you can see their demographics up here. And we first asked them, have you ever used these services, and if not would you consider using the services? And about 6% of our respondents reported that they had used the services, and 64% said they would use the services even though they hadn't done so. Then we asked them, why would you use the services? And over 80%, they could choose more than one answer here. Over 80% said they just had general curiosity about these genetic testing services. More interesting to me was that over 70%, about 73, 74%, said that they would use these services specifically to see if a disease ran in their family or was genetic. So they were interested in it for healthcare purposes. And also very interestingly, about 40% said they would use the services to learn about their genetic makeup specifically without having to go through a doctor. And we didn't get to kind of follow up on that and probe into why that was so important to such a large minority of our respondents, but I think that's an important issue that deserves further exploration. So we asked them a bunch of questions and relevant to what we're talking about right now, we asked them whether they considered the information you would get back from these companies to be a medical diagnosis. And of that small 6% of our respondents who said that they had used these services, 60% considered the information they got back to be a medical diagnosis. Of the 64% of individuals who were interested in using these services, just under 40% said they would consider the information that they would get back to be a medical diagnosis. Finally, we were interested in sort of how is this information from a policy perspective going to interact with our healthcare system and the practice of medicine. And so we asked individuals that had used the services, did you talk to your physician about your results? And about 55% said yes, they had spoken to their physicians about their results and another 10% said they hadn't that they planned to. But remember, this is only 6% of our respondents, so it's a very small number of people. Those who said they were interested in the services, just under 80% said they would talk to their physician about their results. And then we asked everybody, do you think that physicians have a professional obligation to help individuals understand results from these direct-to-consumer companies? And about 60% said agreed or strongly agreed with that statement, that yes, physicians have a professional obligation to help patients understand this information. So just as a point here, there was a follow-up, much more rigorous study that was recently conducted out of Eric Topol's lab. Cinnamon Bloss published a New England Journal of Medicine I think just this month. And they did a much more intensive survey and study with over 2,000 Navigenics consumers. And what they report in their findings was that 26.5% of their respondents reported that they had shared their results with physicians. So it may be that people think they're going to share their results with their physicians and they're not actually doing it. I think we need a little bit more data to understand that and piece that out. Regardless, however, this research and the results of our survey raised for me a lot of questions about sort of the healthcare ethics and implications of this. So I was really interested in, well, what are physicians supposed to do when patients come to them with this information and how is it going to interfere with or enhance the physician-patient relationship and what are the obligations of healthcare providers? And so I partnered with a colleague of mine, Wiley Burke, and we started thinking through these issues from an ethical perspective and wrote an article where we were kind of teasing out the appropriateness of acting on some of this information. And I think one of our main points there was when you have genetic information that you get back that has uncertain or unproven clinical utility, there may be a tendency to want to try to follow up on it because that's what, as healthcare providers, we typically do, is try to follow up on stuff and find out the answer. And if it's truly the science is not there, then we make the argument that to follow up on it might not be a justified use of healthcare resources and it could also pose additional risks and create iatrogenic harms for patients. So coming off of sort of that ethical analysis and the discussion that we had had, it brought us back to sort of the legal issues and we became interested in the regulatory issues of should these companies be regulated more than they are currently being regulated? And this issue really kind of came to a head last summer when FDA announced its intention to start regulating direct-to-consumer genetic testing companies and genetic testing labs more generally. And so in the last couple of months we partnered, Wiley and I partnered with some lawyer colleagues of Barbara Evans and Tim Caulfield again and we really did sort of a more in-depth legal analysis of how the FDA possibly could regulate this versioning industry with all the complexities of the genome-wide type of testing that they're doing. So hopefully that gives you a sense of sort of how the legal analysis that we initially did informed kind of the empirical questions that were raised and then our empirical study informed our ethical analysis which raised additional legal questions. I think now we're at the point where there are additional empirical questions that we'd like to study and I've started collaborating with Robert Green and Scott Roberts who've done some really, really fascinating work on outcomes measures and how patients react to certain genetic risk information to look at it in the context of direct-to-consumer testing. They have a big grant and I'm consulting on that grant and they're doing some really neat work in that area. Okay, the last theme that I kind of wanted to talk about is the expansion theme and here I think I've already sort of brought this up in some ways. The fact that ELSI research in general has really outgrown its place solely within the context of NHGRI and it's a much broader area of research now. It's also in some ways outgrown its exclusive emphasis on genomics. I think there's a lot of other diseases and conditions that are touched by this. I would argue that all areas of medicine and research have ethical, legal, and social implications that deserve serious consideration and study. And so I think that in some areas of research and medicine there are unique ethical, legal, and social implications and it's also the case that some of the issues that we study in the context of genomics have direct impact on researchers, investigators, and other areas of health and disease and that are funded by other institutes at the NIH. So one example of this has to do with data sharing and I've spent quite a bit of my time working on the issue of data sharing and as you all probably know NHGRI has had a very liberal culture and policy around data sharing since the beginning of the Human Genome Project. They have called for the rapid public release of all generated sequence data since the beginning of the Human Genome Project and there have been several data sharing policies and published in that spirit. In the last couple of years I think there's been increasing concern about the ethical implications of public data release and concerns coming out of some of the informatics research that's been done showing just how easy it is to identify an individual on the basis of their genomic information. There's been concerns about whether these types of policies appropriately strike the right balance between advancing research and protecting individual research participants and their privacy. And so the latest NIH policy on data sharing which was for genome-wide association studies calls for the release of all GWAS data into dbGaP which is a controlled access database and you have to apply for access to dbGaP through a data access committee so this creates an extra layer of protection. So you'll notice that this is an NIH-wide policy. It's not restricted to NHGRI and there are a lot of investigators at NHGRI who are conducting research that would make them fall under this data sharing policy. And at some institutes I think there are special issues that come up that complicate the issue of data sharing and just one example of probably many is the National Institutes on Drug Abuse and they held a workshop a couple years ago that I attended. And the sole purpose of this workshop was to think through some of the ethical challenges associated with data sharing when you're dealing with sensitive information like in a social environment and psychosocial information and you're merging that with genetic data. And so this gives you a sense of sort of how the issue of data sharing really touches a lot of different institutes and a lot of different researchers. I got engaged in the issues around data sharing again through collaboration with our genome center. This is actually how I got interested in the whole field of genomics and the whole foundation for the genome center where they were really concerned about releasing their individual level participant data into publicly accessible databases and this was about in 2005, so about two years after the genome project finished. And so Richard Gibbs and I worked on this quite a bit and I went to all of their lab meetings and spent a lot of time over at the genome center trying to understand the issues from their perspective and then went back to my office in the Center for Medical Ethics and did a lot of legal research and did a lot of ethics research and spoke to a lot of colleagues and tried to get a handle on what some of the issues were. And we published this paper back in 2006 and made several recommendations for managing the issue of data sharing. One of our recommendations was that since the decision about data sharing necessarily involved a tradeoff between individual privacy and advancing research that people are going to differ in terms of how much they care about their genetic privacy and so we should leave that decision up to individuals in the consent process. One of the biggest policy pushbacks we got on this was, well if you tell people about data sharing and you ask their permission and you give them a control over it nobody's going to participate in research and nobody's going to share their data publicly only what Zach Kohane and Russ Altman call information altruist, which are those people who have very little concern about their genetic privacy are going to be participating in public data sharing. So we decided to test this more empirically because it seemed like a legitimate concern but wanted to see what participants felt about this. And we started by doing some focus groups with individuals who were participating in a genetic epilepsy study at Baylor and from our focus groups it seemed that they were very interested in the issue about data sharing. They seemed to want to get engaged in the decisions about data sharing and we developed a couple of consent models that we ran by them and got their feedback on and modified in response to a randomized trial of three different types of consent that dealt with data sharing and really the only thing you need to know about this for these purposes is that each of the consents only varied in terms of how much control they gave participants about data sharing. So the traditional consent here just simply said we will share your data both in publicly accessible databases and controlled access databases binary consent gave them an opt out so you could participate in a study and you could choose not to share your data as you liked and tiered consent gave them three choices you could participate you could share your data publicly you could only share your data in controlled access databases or you could not share your data at all. We then debriefed participants we showed them all the consent options allowed them to change their mind and invited them to participate in a follow-up interview. We partnered with these six studies at Baylor that were ongoing and were recruiting participants and you can see about half of them in an autism study and we worked very closely with these investigators all of these studies were collecting samples and they were potentially using them for genetic analysis and they would involve broad data sharing. We randomized 323 individuals and surveyed about 230 and are just very briefly our main findings was that initially this is pre-published data but initially about 84% of people agreed to public data release regardless of what consent form they had been given and everybody who had been randomized to the traditional consent where they didn't have an option agreed to participate in the study so nobody said I'm not participating in this because you're telling me you're going to release my data. After we showed them all their options about 53% stayed with their decision to release their data into publicly accessible databases about a third chose only to release them into restricted databases and about 14% chose not to release them at all. Other key findings that we found through our interview process and this is sort of just the summary of some of the findings that we found more qualitatively people seemed very willing to share not only their genetic information but also their clinical data but they seemed to draw a line at personal information and this is defined as name social security number address things like that. There was also a tremendous amount of trust in researchers and in the research institution and I think this contributed to people's willingness to participate in the research to share their data more publicly and finally we asked participants do you want to be involved in the decision about data sharing and the vast majority said yes when we asked them how do you want to be involved overwhelmingly we heard just ask me about it I just want to know about it and I want to be asked about it and when we kind of probed that more qualitatively we found that this really wasn't about primarily about concerns about their privacy it was about respect it was about feeling respected as a research participant and feeling like they were being treated respectfully so I'm presenting all of this to you really to kind of make the point that this type of research has implications I think for all areas of research funded by all NIH institutes not just genome research there's a lot you know we had cancer researchers funded by NCI we had neurologic researchers funded by other institutions and so this has implications for all of them so I'm going to move forward in their research so I'll just bring us back to our three themes and just to highlight these again and I just want to reiterate one more time that I'm presenting you with my experience and my sort of narrow lens at which I'm looking at these three themes I do think they're important themes and I hope that this can contribute to a discussion about the best ways that we can integrate, collaborate and expand so that LC research has the greatest impact on science as we move forward in the next decade and I said I'm a multidisciplinary researcher so this is a multidisciplinary team of investigators that I'd like to acknowledge thank you