 Thank you, all. Good afternoon. It's a pleasure to be here. Thank you, Terry, for the invitation. I'm going to talk just very briefly, highlight some of the recommendations that the Presidential Commission for the Study of Bioethical Issues made in its October 2012 report called Privacy and Progress in Whole Genome Sequencing. This is the copy of the report here. It is available at bioethics.gov, where all of our reports are. This one specifically of interest to you, I'm sure, if you have not already seen it. It is available there. This report was one of the reports that this commission was interested in in terms of its forward-looking work, concerned about large-scale sequencing and privacy and what that might mean for both in the research context as well as in the clinical context. And so while there are a lot of ethical issues clearly associated with large-scale sequencing, we had to actually complete a report, so we decided to choose a topic, and the topic we picked was privacy. Not an easy one, not a small scope itself, but there were plenty of ethical things to chew on in terms of privacy and progress. So we did choose that. We are currently working on another aspect that kind of tumbled out of this topic, which is incidental findings, and our commission is currently taking on that issue, though we do speak to it briefly in this report. We considered five basic ethical underpinnings or principles, if you will, as we talked about privacy and progress. The first, respect for persons, sound familiar to most of you, which highlighted the real need for consent, not just a consent form, but the consent process. Secondly, responsible stewardship, that is appropriate oversight and management of data collected through whole genome sequencing or large-scale sequencing, as well as responsibility across a project. Every person, whether they're the PI, the data manager, the data collector, the IT person, every person who has contact with these data, these big data, whole genome or large sequencing data, has responsibility, personal and professional responsibility to respect these data, and that was something really important, which came out in one of the recommendations here. Intellectual freedom and responsibility is our third principle here, where we really wanted to be clear that we were recommending models for broad data sharing to allow for individuals who are very interested in sharing their own data for the progress of science to have that happen, while at the same time allowing for people not wanting their data to be available to others to let that happen. In a context of regulatory parsimony, so that is a concept we introduced in our very first report in 2010. The fourth principle, democratic deliberation, we recognize that there will be a need for changes in policies and practices. This is a very dynamic field, and we wanted to be clear that our approach needed to be agile and flexible as this field moves forward. Evolving science requires us to be evolving in our policies. And finally, justice and fairness, we wanted to ensure that both the burdens and the benefits of this really important science was fairly and justly distributed. So we came up with, the commission came up with five areas where they made recommendations. The first was a strong baseline protection while promoting access and data sharing. So it sounds a bit contradictory, but the idea was to create a very safe space, because we know we need a lot of data to do good science in large scale sequencing, so we needed to ensure that the protections were very strong so people would be willing to participate. So creating this strong baseline protection so we could promote access and sharing. Our first recommendation was to maintain or establish very clear policies that defined acceptable access and permissible uses for these kinds of sequencing data. That would allow models for data sharing by individuals who really wanted to share. We heard from a lot of folks that they really, you know, people very interested in ensuring their data get used to find cures and preventive measures for their illnesses. Our second recommendation in this area was to ensure that there was a consistent floor of privacy for folks. We found that in the 50 states there were 50 different ways that privacy and confidentiality were protected. In about half the states it is not illegal to take someone's coffee cup, take a swab of their saliva and have it sequenced. We thought that there should be some consistency across states, so we recommended that a floor of protections be developed. The second area that was really important, a wide area, was data security and access to databases. We felt like all persons, this will sound familiar, but all persons who work with genome data be guided by professional ethics and ethical standards and be held accountable for any lapses or negligence in use of data, whether those are used recklessly or accidentally. The second recommendation in the security area was that data should be stripped of any traditional identifiers whenever possible, when at rest, or even when in use if at all possible, and that there should be only exceptional circumstances when entities such as law enforcement or other kind of security agencies have access to data for any non-health related purposes. And finally, the third recommendation in this data access and security area, that third party and trustment of whole genome sequence be particularly evaluated and they interpret and hold genome data and sequence data according to relevant regulatory schemes, including HIPAA, whatever else. So we know that these data are big data and they're hard to store on a PC or laptop, that we do need this cloud computing and such, and anyone who holds these data should be required to do so according to industry standards. We also mentioned here that best practices for security, for keeping data secure should be freely shared across the industry, not kept as possible marketing or possible a leg up in some way for the cloud, for somebody to store data. They should in fact be shared, this is a common good or a public good not to be used as a competitive edge. The third area of the five was consent, and in this area we did recognize that there's a big difference between the consent form and the consent process, and we did hear from many people that there were many different ways to gain consent for these, for the use of these data, and many people had really strong feelings about which was the best way. There were however few data about which were the best ways, so what we recommended was that researchers and clinicians should evaluate and adopt robust and workable consent processes, and we should really understand who has access to the data, for what reason and how these data might, people who participate in these studies should understand how these data might be used in the future. It's important to ascertain consent and preferences at the time the samples are obtained. We also heard from researchers that there was a lot of confusion about what should be in the consent form, what's the minimum amount of information, some consent forms were numerous pages long, others were very short, people didn't want to overload or under load people with the science, so we did also recommend that OHRP or another organization established some clear guidelines for what should be in the consent form. We also felt this is where we talked a little bit about incidental findings that individuals should be made aware that incidental findings are likely to occur or be discovered, and they should be told whether these findings will be returned and to whom. In addition to that, we thought it would be important to support studies, and we recommended that people support studies to evaluate proposed frameworks for returning or offering the return of incidental findings and investigate what participants' preferences are, and there is some work, obviously a body of literature in that now as well. To facilitate progress in whole genome sequencing, again to move the science forward, the science is critical and will have enormous benefit both to individuals and to public health. We think it's critical to facilitate, we recommended that relevant clinical entities and the commercial sector actually should facilitate explicit exchange of information between genomic researchers and clinicians while maintaining this robust data protection and safeguards. It's that safe space so people participate. We also felt that recommended that policymakers promote opportunities for the public to benefit from whole genome sequencing research, and the community should promote opportunities for exploration of alternative models between researchers and research participants, things like participatory models and collaborative relationships between participants and researchers. Finally, the public benefit. We thought that it makes most sense for the federal government to facilitate access to the numerous scientific advantages and advances generated through the investments in whole genome sequencing to the broadest population and group possible and to ensure that all persons who can benefit from these scientific advances do so. So in summary, those are our recommendations from the report. It's a rich report of a hundred pages or so. I gave you just a very high-level overview, and if you haven't already taken a look at it or you're interested in any of the specifics about any of those recommendations that I went through, I would really encourage you to take a look. Again, it's bioethics.gov and our contact information is there as well, our email address is info at bioethics.gov, but a very important set of recommendations for this fast-moving and fast-changing science. So we'll take questions. I guess we have a few minutes for that, I'm assuming. Okay. Great. Thank you very much. Okay. Great. Anybody? So questions for the Office of the Assistant Secretary? Yes. Thanks. The issue of informed consent forms and processes, I think we all know it's been broken for a long time. OHRP has not really been forthcoming with helpful new approaches to this, and where the rubber meets the road, things are being added on, such as you just said for incidental findings, you should include what and to whom and whatever. We have to include stuff for DB Gap. We have to include stuff for CT.gov. I mean, the various agencies have got to get together and figure out how are we going to get this information across? I think the short consent form with all of the things we have to put into it, A, I think it's difficult for people to understand what it is they're signing up for, and two, short is just not an option. So I truly think we need some major work in this area, but I think the efforts so far have not been very productive. So I guess it was more of a whining than a question. Well, since we're here, we'll have to take the hit for that one, but no, thank you for your comments, and we'll obviously relay that to OHRP, and I'm sure Dr. Menecoff. You really thanked me for that comment. Well, I think we need to hear everything. Well, I think certainly Dr. Menecoff, who I think hopefully many of you have worked with, you know, I think he's an excellent scientist, he knows this space really well, and very easy to work with. So certainly if there's a way, if this is a space that you all are interested in from your perspective here, he'd be happy to engage with you on that. I mean, these are complicated issues, particularly when you talk about human research protections and the common rule, which is 17 federal departments coming together and changing things take time. In fact, it hasn't happened in about 20 years. So obviously there are changes that need to be made, and folks are working in this area, but I think I'm sure Jerry would welcome conversations with you if you had specific suggestions on how to improve the process. I will add to that that one of the things we did hear from researchers was that they weren't sure how to do this balance between too much information and too little. This informed consent, the informed part is just very confusing. You can have 30 pages of, you know, a genomics 101, and that's not informing anyone of anything. So we really were hearing that people wanted a balance. And so in our recommendation, we did, we recommended, you know, four or five basic things that we thought we heard from researchers that they thought would be useful to be in there. And we've actually had conversations with OHRP about implementing that recommendation. So we've begun talk with them about how to create some guidance for that. Now it right now doesn't, it is not a requirement that certain things be in there, but researchers obviously feel compelled to put certain things in there because they want to inform participants. So, but we are, we are, we have begun talks with, with Dr. Manikoff and his staff about how to make that accessible without being overwhelming. But again, it's a very long process to change policy, as we all know. Yes, go ahead. So is interested in your findings, the distinction between clinical written consent documents for genome sequencing need not be as detailed as research consent documents, but with the obvious implication that they need to be done. What we're seeing now is a proliferation of panels of tests with 30, 50, 50 genes often, often packaged together. And it's, you know, and these vary from genes that can cause cancer, P53, very important genes, to cytochrome panels. And, you know, nobody really cares whether what your CIP 2D19 profile is, frankly, that's not a, and is that different than, than testing the serum creatinine? Are we practicing reverse genetic, well, no, just genetic exceptionalism because it's DNA we need to consent. So I'm, I'm interested in your, your thoughts about the spectrum of genetic testing as well as the difference between clinical and research applications. This is an excellent question. There are some, where this comes from is there are some differences between when you do, you know, you take someone's, measure someone's hematocrit. You know what that means. You know how to interpret that. There's not anything that we're going to find out about that in the future that we go, oh my gosh, your hematocrit of 14 really meant, but there are those things when we do large, you know, like whole genome sequence or whole exome sequence, we're going to find things that we don't know what they mean yet. So we all understand in this room about what it, what things are, what the different qualities of a whole genome sequence, what makes this unique? Not only are we discovering things that we don't know what they mean yet, and they're in the record, right? Like, you can't take it out. You can't get rid of it. It's there forever, somewhere forever associated with this patient forever. And it's also reflective of this patient's blood relatives. So we've got that piece of it too. So there are things about it that are different. Exceptional, I, you know, I don't want to use that word, but there are qualities of these tests that are different. Just like when we image someone, we risk that we'll find something else. Different qualities, okay, it's not about their parents or their to be born children, but there is a risk that we'll find something we didn't expect when we image someone. Okay, so that's kind of a unique characteristic of imaging someone. We have to tell them about that. Just like when we do this, we have to tell them about what kinds of things we, what the risks are for the test. So it's not exceptionalism in the sense that we're, we're asking for something different. We're asking for the risks of this test versus that test. The risks for drawing someone CBC are pretty straightforward and low and we know what to tell them. We're going to find this, this and this. And there's not really anything too risky about that. We do your whole genome sequencing. These are the risks. They're different. And we have to do something with those. So that, that may be a debatable point that we could go on debating for some time. We do need to move on. I know we had two comments. You had one. Can yours be really quick, Mark? Yes, and that is that coming back to Pearl's point, I think that as we think about takeaways from today's meeting, in other words, what are things that we can aggregate around and perhaps do something about. I would say that this privacy and data sharing is a perfect topic to look at bringing the people that are around this table together and see if there are some things we can do outside of major policy changes where we can bring some, at least some clarification and resolution. Yeah. Thank you very much. Thank you guys very much. Okay. Next we have Dr. Joseph Selby from the Patient Centered Outcomes Research Institute.