Health Council of the Netherlands

Transcription

Dr. Sally Howard: Good morning. Welcome to NIH Natcher Center. My name is Sally Howard. I'm the Chief of Staff to Secretary Kathleen Sebelius here at the United States Department of Health and Human Services. It's my distinct honor to welcome everyone to this international consultative workshop on highly pathogenic avian influenza H5N1 viruses. I hope you're all getting yourselves situated. It's a nice early start to the day, on a nice drizzly day at that. The Department of Health and Human Services is the United States' government's principal agency for protecting the health of all Americans and for providing essential human services for those in need. These missions are underpinned by biomedical research, which yields the fundamental insights and practical knowledge that moves us from basic discovery into therapies, treatments, and cures for tackling both chronic health concerns as well as emerging disease threats. The biomedical research mission of the Department is carried out for the Centers for Disease Control and Prevention, the federal Food and Drug Administration, as well as the National Institutes of Health, the host of today's meeting. Our topic for the next two days, highly pathogenic avian influenza, is pertinent to the research and public health missions of the Department, but, as importantly, it is an issue of major concern around the globe. Highly pathogenic avian influenza has long been recognized as a significant agricultural problem. It is widespread among poultry in parts of Asia and the Middle East, and to date has caused an estimated $20 billion U.S. in economic damage across the globe. More worrisome is the possibility is that HPAI H5N1 will become a major public health threat. We already know from experience that this virus is capable in some instances of jumping hosts and moving from avian species into humans, causing severe respiratory illness. This is thankfully a relatively rare event, but when this leap occurs it can be quite lethal. Some 600 human cases have been reported since 2003, with a mortality rate of approximately 60 percent. Although currently H5N1 is not well adapted for sustained human-to-human transmission, recent studies underscore the growing concern that the virus may acquire this ability, and thus the importance of understanding this virus and its potential to become a pandemic disease agent. Research into this virus may prove critically important to such public health activities as surveillance of naturally occurring strains of influenza; development and evaluation of countermeasures such as vaccines, antivirals, and diagnostics; and enhanced preparedness and response strategies. There are different approaches for studying the ways in which the H5N1 virus can spread, adapt to new hosts, or become more pathogenic. One approach is to engineer into the virus genetically-based traits that mimic those that might occur in nature. These so-called gain-of-function experiments are not without risks, however, and have generated much discussion over biosafety and biosecurity issues. I think we all remember about a year ago reading The New York Times article that talked about the doomsday virus. I think that launched us off onto a very vibrant discussion about this type of research. These safety and security concerns are global in scope and thus any path forward for this type of research must be developed through an international dialogue, and hence the purpose and value of today's meeting. Here at the Department of Health and Human Services, we've had extensive discussion about the analytical framework that should govern our decision-making when considering HPAI H5N1 gain-of-function research. The discussions over the next two days will provide important insights to consider as we finalize our approach to decisions about the type of research we should fund, and can also inform your own considerations of these issues in your home countries. In light of that, it is especially gratifying to see the robust participation at this meeting from countries around the globe, including those for whom H5N1 is an ongoing agricultural and public health concern. I know those from -- there are a number of people from Southeast Asia in attendance. We're glad to have you share your views about the value of the research, its potential risks, the risks to public health preparedness of not doing the research, which again is the counter to the biosecurity risks of doing this research, and the principles that should guide any research in the future. I'm also pleased at the different expertise that is represented. There are four very distinguished panels. Actually, now I'm seeing six. Six very distinguished panels that represent a range of expertise from public health, science, biomedical research, biosecurity, and biosafety. In concluding my remarks, I want to express the gratitude of the United States Department of Health and Human Services to everyone for making the journey to be here today and to be a part of advancing this dialogue. I know it will be very helpful as we move forward. Without further ado, I'm now going to turn the proceedings over to the co-moderators of this meeting: Dr. Robbert Dijkgraaf and Dr. Harvey Fineberg. Dr. Dijkgraaf is co-chair of the InterAcademy Council, past president of the Royal Netherlands Academy of Arts and Sciences, and Director of Institute for Advanced Study at Princeton. Dr. Fineberg is President of the U.S. Institute of Medicine and professor of health policy and management emeritus at Harvard University. And I'll be very remiss if I did not thank Amy Patterson and a number of those at NIH for all of the hard work that they've done in pulling together this very fine agenda and making sure that you all were invited to attend. So, thank you very much. I look forward to hearing from you in the next two days. [applause] Dr. Robbert Dijkgraaf: Thank you, Ms. Howard. Ladies and gentlemen, it's a great honor for me to serve as co-chair of this important meeting. And the subject matter, gain-of-function research on highly pathogenic avian influenza H5N1, is a topic of special concern of course to scientists across the world, but also one which the scientific community in the Netherlands has given a lot of thought. So it's got very active researchers working on this and understanding the agricultural and public health threats. In fact, we -- in the Netherlands, we had a very active public discussion, wide ranging, including many opinion leaders and policymakers. It's also of interest because some of this work fits perfectly, the characteristic of dual-use research of concern, a reference to important scientific work that can nonetheless yield information and technologies that in the wrong hands could be misused to cause great harm to the public health or global security. This dual-use question has been a topic of concern to the Royal Netherlands Academy of Arts and Sciences, which actually spearheaded the development of -- both nationally and internationally -- the development of a biosecurity code of conduct that emphasizes awareness raising, oversight, and accountability among scientists. And these are themes that have great pertinence to our aims today, as well. In charting a path forward, it's essential that scientists enter into a dialogue with those who have other perspectives, including security experts, safety experts, and the public at large. And the opportunity for that is what makes this meeting, I think, so significant. It's a unique occasion to have the kind of transparent conversation among our communities that's essential if we are to safely and responsively advance science, but continue to earn the public's trust. This is a conversation that must cut across not only many disciplines, but -- which are rightly represented today, luckily, but are also many countries and inter-governmental organizations, which is a global problem. On that point, I'm particularly gratified to see an ample representation from countries across the world. I expect to hear very diverse points of view and that is a good thing. The organizers have made every effort to represent a balanced representation of the issues as possible. And it's important to emphasize there are no foregone conclusions in this workshop; all points of view are fair and will be taken into account by the U.S. Department of Health and Human Services and by all of us at this meeting in charting the best course forward. And certainly this issue is a prime example that I would say motivates a coordinated global approach. Because of this diversity of views and the challenges posed by balancing the hopeful benefits of this research against its potential risks, I'm confident that the next two days are going to be extremely interesting and very enlightening. So, with further ado, I'm now going to turn the proceedings over to my co-moderator, Dr. Harvey Fineberg, President of the U.S. Institute of Medicine, who wills ay a few words, as well. Thank you. [applause] Dr. Harvey Fineberg: Well thank you, Dr. Dijkgraaf, and good good morning, everyone. It's my pleasure, also, to serve as a co-chair for today's program and tomorrow's. In one sense, we're dealing with a very circumscribed topic, highly pathogenic avian influenza H5N1 virus, but in a larger sense the subject of this meeting literally affects every individual in the world; every citizen in every country has a stake in the research that will or will not go forward with respect to these highly pathogenic agents. For those of us here today, we have an extraordinary opportunity to share with one another our perspectives, our ideas, our concerns, our aspirations, with respect to this research. Our aim, in a sense, over these two days is two-fold: on the one hand, we do have a draft framework prepared by the government through the Department of Health and Human Services for which we will all have an opportunity to comment in these days and beyond. So we are eager to seek your views on that framework. But, in a larger sense, this meeting is about advancing a global dialogue on the issues that directly and indirectly emanate from research with this highly pathogenic agent that has the character of dual-use that Professor Dijkgraaf referred to. In the course of our deliberations over these two days, we're going to be organizing our discussion through a series of panels, each of which will deal with a discrete topic. Each of those panels will have an opportunity for the individuals to present their views and we will then have the opportunity, indeed the desire, to hear from those of you who are here for you to express your perspective, your opinion, your concern, and your desires. We want this meeting to be a place where we can invite every point of view to be expressed openly, candidly, in a forthright manner, and respectfully. We invite you to think and to share. Dr. Dijkgraaf and I will be very active listeners in the course of this discussion and we urge that all of you also be active listeners in the course of this discussion. In the concluding panel tomorrow, we'll have the opportunity to hear from the co-moderators of each of the other panels and offer an overall perspective on insights and lessons from this gathering. It's very important for us to keep in mind that our aim is not to reach a consensus amongst those here or amongst the panelists or in any group that is represented here. Our goal is to share and to hear individual points of view so that they can inform both the framework and the larger dialogue that surrounds these issues. Our topic, of course, is of course centrally focused on the safety and responsible conduct of research. And the research program in the United State government is focused particularly on the work of the National Institute of Allergy and Infectious Diseases here at the NIH. And we are very privileged, in opening our conversation over the course of these two days, to be able to hear the perspective of the Director of the NIAID, who in this audience needs no introduction, but it is for me a great pleasure and a source of privilege to be able to introduce to you the director of the NIAID, Dr. Tony Fauci. [applause] Dr. Anthony Fauci: Thank you very much, Harvey. It's a great pleasure to be here with you this morning. I want to take this opportunity, as you see on this first slide, to first welcome you all. I know I see so many friends and colleagues in the room who have travelled a great distance to be here with us today to discuss this extraordinarily important topic, but also to give a brief overview. As Harvey said, a considerable amount of the activity that goes on in this area from a research standpoint comes from the NIH and NIAID. As you know, we're part of the Department of Health and Human Services, as is the Centers for Disease Control and Prevention, who also have a considerable amount of contributions, both from a public health surveillance as well as from a research standpoint, in the topic today, which is gain-of-function research on highly pathogenic avian influenza H5N1. So what I'd like to do is to give you a perspective historically -- briefly, but historically -- about how we got here today to discuss with you in an open forum, represented by many different perspectives, in the questions that we'll be asking today. So, from the standpoint of research in general, we at the NIH and the CDC have been involved in the study of influenza literally for decades and decades. I don't need to tell this audience, but I know there are those who are listening in who may not have the historical perspective, is that seasonal influenza itself is an extraordinary threat to global health, resulting in approximately a half-a-million deaths per year worldwide. Every once in a while, unpredictably, we have a pandemic. History has shown us that pandemics occur and almost certainly will continue to occur. On this slide, you see the history from the last century and this century of the now iconic pandemic influenza of 1918, which killed between 50 and 100 million people. A serious pandemic in 1957, again in '68, and then most recently in 2009, the first of the pandemics of the 21st century. Now, highly pathogenic avian influenza, as you've heard from Sally, is widespread among poultry in parts of Asia and the Middle East. Infections of humans, i.e. jumping species, is rare, but when it occurs, it occurs and causes severe respiratory illness. Currently, this virus is not well adapted for sustained human-to-human transmission, but there is concern that has been going on now for approximately a decade -- in fact, the first cases were in 1997, but since 2003 there has been considerable concern that the virus may ultimately acquire the ability to adapt itself better for human-to-human transmission. This is the now familiar map of the worldwide cases as of just a few weeks ago. As Sally mentioned, there are about 600 cases, but, importantly -- and I'm going to get back to that in a moment, because this is one of the issues which actually brings us here today and caused the discussion that has been intense over the last 13 to 14 months, and that is the 59 percent -- the reported 59 percent mortality, which makes this a most, most unusual smoldering, pre-pandemic threat. Now, back in 2003, when the cases began to accumulate, there was considerable concern at the highest level of the federal government, including HHS -- which, as you know, is the one with the biggest stake from the standpoint of action in this area. So, on this slide you see in November of 2005 the federal government came out with a pandemic influenza plan, and immediately thereafter, as part of that, HHS came out with our pandemic influenza plan, and then the next year an implementation plan came out. I tell you this because some of you, as I know in our discussions, are not fully appreciative of the historical nature of how we started getting involved in an intensified research in this arena. On the right-hand slide of the slide you see the strategy and implementations that were outlined in these documents, and this is one that comes from our HHS pandemic plan: international and domestic surveillance, vaccines, antivirals, communications, and state and local preparedness. Several of these mandates were for the CDC, several for the NIH, and some overlapped among -- between the two agencies. The two we're going to focus on now is vaccines and antivirals, which was the mandate that we as a research institution were given as part of our already ongoing decades of work on influenza in general. As part of our research endeavors, clearly interventions in the form of diagnostics, therapeutics, and vaccines were important. But on the lower part of the slide, you see basic research, and that has always been and will continue to be an important part of our mission and our activities. If you look at basic research as we've approached it, through the years, long ante-dating the appearance of H5N1 highly pathogenic virus, as part of that influenza basic research was intensive study of host adaptation, transmissibility of influenza viruses, pathogenesis, and virulence. And integral to that study has always been the issue of gain-of-function research, not only for influenza but essentially for all infectious diseases research. Now, there are a few ways to look at gain-of-function research. There's the naturally occurring mutations which naturally give gain-of-function, and investigators study these effects on the phenotypes of interest. Does this mutation make something more transmissible, more pathogenic, or adapt to hosts better? Or, what historically investigators have done, is to actually create gain-of-function by making mutations, passage adaptation, or other newer genetic techniques, such as reverse genetics and genetic re-assortment. When we do that, often some phenotypes appear and others disappear. For example, it is commonly seen that when you increase a transmissibility, you may see a decrease in pathogenesis or vice versa. You may deliberately increase pathogenesis and see a decrease in transmissibility. But the bottom line is that gain- and loss-of-function research is critical to understanding disease pathogenesis, antimicrobial resistance, and host responses, as well as to developing better techniques of surveillance, vaccines, and therapeutics. Specifically to gain of function on HPAI H5N1, what we're talking about now is the gain-of-function research in studies that increase predominantly the transmissibility, as was -- is the case that I'm going to get into in a moment -- as well as pathogenesis and alteration of host range of the virus. Now, the reason we are here today in this room, with H5N1, highly pathogenic influenza, and we're not in this room discussing so many of the other gain-of-function research that we do, is because naturally-occurring HPAI H5N1 viruses cause a reported almost 60 percent mortality in humans, which triggered a concern, understandably, clearly, that if you give a gain-of-function of a pathogenic virus to make it more transmissible that's a whole different story than some of the other things we faced. So let's get down to what happened, very briefly. You know historically -- I'm going to go very quickly through the historical perspective that brought us here today. There were studies done by two NIH/NIAID-funded investigators, Ron Fouchier and Yoshi Kawaoka, in which H5N1, a strain from Indonesia and a strain from Vietnam, were altered in a gain-of-function either by direct mutation or by re-assortment. And by passage in ferrets, the mammal model for this virus for humans, there was an increase -- in fact, a development of aerosol transmissibility in a mammal, which this particular virus did not have. Because of that, this triggered concern. This was after the experiments had been done and after they had been submitted to the journals. And from this press statement, we put it before our National Science Advisory Board for Biosecurity here at NIH, which is representative and advisory to the entire department of HHS as well as to other agencies. And the conclusion was made, and this is critically important for us to understand and I take this right out of the statement that came from the NSABB, that due to the importance of the findings to the public health and research communities the NSABB recommended that the general conclusions highlighting the novel outcome be published, but the manuscript did not include methodologic and other details that could enable replication of the experiments by those who would seek to do harm. What was also discussed: that might accidentally be released. So it is not just people who would deliberately do harm. As Sally mentioned, following that there was an explosion of reactions, sometimes bordering on the very extreme as shown by this editorial from The New York Times, "An Engineered Doomsday." This is just one, but, as some of you may recall, there was a lot of activity talking about worst-case scenarios where the world might be destroyed. In that setting, the influenza community voluntary imposed upon themselves a pause of 60 days from January 2012 on any research involving highly pathogenic avian influenza virus leading to the generation of viruses that are more transmissible in mammals. That was supposed to be a 60-day, and, as you know, the moratorium is still in place, the voluntary moratorium on the part of part of the investigators. But soon thereafter there began to be an open discussion clarifying that research in different for a outside of the NSABB. The NIH and the CDC, because we do similar work, also agreed that we -- in our own intramural investigators -- we would refrain from these types of experiments and essentially abide by the moratorium that was signed on by a significant number of our extramural investigators. And I'm talking about the investigators at NIAID and other institutes, as well as the CDC. From there came open discussion. Many of you remember the meeting in Geneva in February of 2012 where, importantly, new data were presented and, even more importantly, original data was substantially clarified, which led that group, which was predominantly influenza people, with a consensus to delay publication but ultimately to publish them after there had been some more emphasis and discussion of safety, public health, and communication issues. But, also, they recommended to extend the moratorium in order to have further discussion, as well as reaffirming the PIP agreement. Then, back in the United States, what happened was a series, as you can see from the dates on these, of open discussions in different forum. There was a meeting sponsored by the ASM on Biodefense. Shown here, the people who were a part of the panel, myself included: Bruce Alberts of Science, Mike Osterholm of the NSABB, and Ron Fouchier, one of the investigators. And we discussed openly the situation of the publishing of these data and the experiments that would be performed. The NSABB re-met the next month and they examined the revised manuscripts with a clarification of data and they voted unanimously to have Kawaoka manuscript be communicated in full, and in the 12-to-six decision also that the Fouchier manuscript be communicated after appropriate scientific review and revision, which, as you'll see in a second, actually occurred. Then we had a National Academy of Science workshop here we looked at the lessons learned. Where did we -- how did we get to where we were and what do we need to do in the future to proceed in a responsible manner? The next day, the publication of the manuscripts occurred, as shown here, in the Nature and Science titles. But the discussion continued, and one of the questions that was asked by the investigators, since this was a voluntary moratorium on their part, is "how long is this moratorium going to go on and what are really going to be some of the guidelines that we can actually follow on the basis of this?" We at NIAID, being the major funders of most but not all of these people, we obviously were connected to that because they wanted to know, "Since you're our major funders, what kind of research will you fund?" There was a major meeting of the Centers of Excellence for Influenza Research and Surveillance this past summer at the end of July and the beginning of August, and, as many of you know, I went up there to address the group. And what I recommended is that they continue the moratorium but that we have the opportunity to discuss in an open fashion, that is not only influenza researchers but people like yourselves. And, in fact, the transcript edited of my discussion at the CEIRS was recently published in Bio, in which I referred to this workshop, and I said the meeting participants would consider the general principles concerning the rationale for risks and benefits of such experiments and what lines might be drawn in their conduct and the reporting back and forth with the funding agencies. And so here we are, and this is the workshop that I was referring to, that will take place today and tomorrow. And the purpose, from the standpoint of -- and I'm speaking from a pure research standpoint -- is to review the key issues related to the gain-of-function of these viruses, scientific public health, biosafety, biosecurity, and, importantly for the decisions we have to make now, is the considerations of the possible criteria for funding by HHS, i.e. NIH/CDC, of gain-of-function research on highly pathogenic avian influenza. As you know, there's a draft framework, that Harvey referred to that we will be discussing in detail and you'll have an opportunity to comment on, to guide funding decisions. And that's the critical point I want to make from the standpoint of the NIH about this gain-of-function research. Now, just to put in perspective, are we talking about a major chunk of what we do? No. As a matter of fact, this is relatively small because the research gain-of-function of transmissibility, et cetera, on H5N1 highly pathogenic is a very minor part, but an important part, of our portfolio. It's part of four flu research projects that contain this. It's around 10 percent of the entire H5N1 portfolio and less than 1 percent of the total NIAID flu research funding, but it has triggered a very important question. Now, I want to close on these last two slides because I believe it's important that you keep this in consideration. First of all, questions have come up about the concern of the danger of people that you fund. NIAID, NIH, certainly CDC only funds and conducts gain-of-function research on H5N1 highly pathogenic avian influenza viruses for researchers who are highly trained, skilled, experienced, and adequately regulated. This issue has not been a major concern about the investigators, certainly the ones that I just mentioned, who clearly fall into that category. That was not the concern. The concern was that the products or information that were generated by these experiments might be used by others in a way that could harm society, either carelessly, in an unregulated fashion, by inexperienced people, or even by deliberate misuse. Now, there are some disagreements, and we've heard them in the broad discussion in those months that went from the time of the moratorium until now. There's disagreements as to the scientific and/or public health value of these experiments, but I believe the people who feel that they shouldn't be conducted are in the minority because even the most concerned members of NSABB felt that the experiments should be done, but the distribution of the knowledge should be restricted. Now here comes the rub: as of today, there is no mechanism to provide restricted access to information regarding research funded by NIH. So if NIH funds a grant, it is assumed that the results will be published. The only mechanism for restricted access is classification right now. NIAID does not, nor will we fund or do classified research. So really the fundamental question with regard to our involvement is -- and the discussion in general -- is the issue is the risk to global health of the work that we fund, the risk of not funding that research versus the risk to the global health of the information, harming society. That really is the critical question. So therefore, even though, as Harvey said, there're going to be no conclusions or consensus, from our standpoint the question is, "Should or should we not fund this research?" And that's the thing that we're going to be concentrating on in the discussions that occur. Thank you very much. [applause] Amy Patterson: Good morning everyone. By way of introduction, I'm Amy Patterson. I've had the pleasure of emailing many of you in the room and I want to extend a warm welcome to you, especially to those who have travelled thousands of miles from countries around the world, countries concerned about avian influenza, both in terms of -- as a threat to both agriculture as well as public health, with some of your nations feeling its impact very, very directly. In a phrase, we are here because of scientific responsibility. While collectively we bring a broad, diverse range of expertise, from infectious disease expertise, epidemiology, public health, countermeasure development, safety, security, ethics, agriculture, law, we bring a wealth of diverse perspectives and opinions on the topic at hand, but what we share is a common interest in advancing scientific understanding but first and foremost a desire to protect public health. And underpinning that common interest is a shared value, a value that when we conduct science it's important for us to not only think about its aims, its purposes, but also about its implications, its potential repercussions for society. And that's essentially why we're here today. I'd like to take a couple of minutes to go over some of the key points that have already been discussed, but to try to pull them together, and then I'm going to talk about some of the practical mechanics of this meeting that I think will be helpful to you. As Tony mentioned, the focus of this meeting is what we are referring to as gain-of-function research. And in the context of this meeting, we are referring to research that will confer new biologic properties by enhancing the transmissibility, enhancing the pathogenicity, or potentially expanding or altering the host range of highly pathogenic H5N1. And as Tony mentioned, the reason that is the focus of this meeting is because case reports to date, particularly since 2003, have underscored the high human mortality associated with human infection with this virus, so the notion of potentially conferring additional biologic attributes to this agent is really what underscores the concern today. As Tony mentioned, researchers in this community of work demonstrated their commitment to responsible -- to science by declaring a pause on the research, a pause on research that would increase transmissibility of high-path H5. That pause has been in place since January of this year and we're just about to close out 2012. The community is seeking guideposts for its own path forward, and while this meeting is not going to make a decision, per se, about that pause, we believe that the discussions here today will illuminate the guideposts that are sought for by that community. And, importantly, this meeting is going to provide a wide range of perspectives, hopefully ideas, concepts that we haven't yet thought of that will inform the Department of Health and Human Services as we finalize our framework for how we will approach making decisions about which of this research we will support, if any, and if we do support it, under what conditions will it be funded and supported? The perspectives that you offer over the next two days are going to be taken to heart as we work to finalize this framework over the next several weeks. We believe, in addition, that this forum will make a significant contribution to the international dialogue on this issue. We hope that the meeting will highlight ideas, perspectives, and approaches that will inform your national efforts, for those of you who come from other countries, and help inform the way that you think about policy, the way you might approach your own funding decisions. And at this juncture, I'd like to quickly review just the topics on the agenda and, again, some of the meeting mechanics that I think might come in handy for you. Our first panel will entail a discussion of HPAI H5N1 gain-of-function research, its design, its trajectory, its hoped-for aims in terms of addressing public health issues. And after a very quick break, we'll segue into the next panel, which will focus on the risks and concerns associated with this research. We'll adjourn for a one-hour luncheon, and please come back promptly because we have a lot to do in the afternoon. First session in the afternoon will involve a presentation of the proposed framework and a discussion, and then we'll move into some case studies that were selected with the hope that they will exercise this framework. And I want to just signal up front, the moderators for all the sessions got together yesterday to talk about the meeting and there's a slight change. The discussion session of panel three, a portion of it will be moved to the end of panel four so that we have more discussion time after we've had the benefit of mot only hearing and walking through the framework, but also having walked through some case studies. You don't have to remember that; we'll remind you when the time comes. That concludes our first day and you're going to have the evening to yourself to rest, catch up with friends and colleagues, and, depending on the time zone in which you normally conduct business, maybe catch up with things in the office. Tomorrow we'll begin a session on identifying the conditions, if any, under which this research should be conducted and we'll close out the meeting with a wrap-up session to capture some of the main points expressed. Now, the portions of this meeting allotted to questions and comments from the audience are extremely important, as Dr. Fineberg and others have mentioned. We ask that if you have a comment or question that you approach one of the four floor microphones located -- actually, I only see two. Are there only two, Joel? At the moment. Okay, all right. We're going to have two floor mics and two handhelds positioned throughout the auditorium. And when you approach the mic to speak, please give your name and affiliation and please make your comments or ask your questions in 90 seconds or less in order to allow as many people to ask questions as possible. I wanted to tell you now that you're going to have the opportunity to submit written comments about the proposed framework, so if you don't get a chance to approach the mic or you think of points you wish you had made or questions you wished you had asked after the meeting, you'll have the opportunity to submit comments. And in your meeting packet, there's a paper that gives you the email box address for that and we'll also post it in slides that we'll show throughout the meeting. This comment period will be open through the end of this -- through the end of the week of December. I think it ends on December 23rd. I'll confirm that. Now, to aid you in communicating the proceedings of this meeting to friends and colleagues back home, a summary will be prepared in the coming weeks and will be made available to you and to the public. Please know that this is a public meeting. We do have members of the press in attendance. And while we're not webcasting this meeting, we are making a video recording of the event, which we will plan to post for the benefit of those who could not be here today. And with that road map in front of us, let's begin our first panel, and I'm going to ask Dr. Dijkgraaf to come back to the podium and introduce the co-moderators for this first session. Dr. Dijkgraaf.