Reason that it was not one of the most devastating epidemics in the history of humanity is because that particular flu decided not to be very lent. We dont get a vote. But the Gates Foundation has mathematical modelers that estimated that, had it been anything like the 1918 flu, 33 million, 37 Million People would have died, and we would not be having this conversation because we would be dead. What happens when these sort of things occur is if they dont kill a lot of people, we just move on, especially when it comes to influenza, which people seem to think is just a word that means i dont feel well. For the first question, i would like to ask tony, maybe you can explain why we would want universal vaccines, how does this work, and how is the pandemic different from what we get every year, and where are we . Ok. Thanks, michael. Very briefly, because i know we have a lot to talk about, but the situation with influenza, as many know, is that unlike a virus like measles, which, if you have a measles virus and you get vaccinated against measles, or you get infected with measles, then you are protected, essentially, for life, for the simple reason that measles does not change from year to year or from decade to decade, whereas influenza is very unique in that it is a virus, a group of viruses. There are different kinds of influenzas that tend to drift from season to season. You need to get vaccinated each year, and you try to anticipate the right match between a vaccine antivirus that will be circulating. Every once in a while, as michael alluded to, you have a very dramatic change, either by mutations or evolutions, from animal influenzas that jump species. It is a big change. The viral inflections we deal with, polio, smallpox, measles, etc. Dont do that. So we are dealing with a continual moving target from season to season and the threat of a pandemic. The title of this session is the quest for a universal flu vaccine. When we talk about a universal flu vaccine, it really is an aspirational goal, the quest being to make a vaccine that induces a response in the body, to the part of the virus that does not change from season to season or decade to decade. The scientists throughout the country and world have been able to identify components of the influence of that really do not change much at all. The critical issue is getting a vaccine to induce a response against that part. A universal flu vaccine is not going to be, today we dont have it and that we flip a switch and then the next month or year we have it. It is a process. If you look at the display of influenza as, they are in two different groups and there are 18 different ages. There is a lot of wiggle room you will have to cover. The quest on the road to a universal flu vaccine will be to take one of the influenzas in group 1, lets take h one, and we know it changes a bit from season to season, to make a vaccine that would cover all the iterations of h1. The next iteration would be all the influenzas in group one. There is group two, with h3 and it. It will be a stepwise process with the ultimate aspirational goal of having a vaccine that you could give relatively infrequently, compared to now. It would cover the broad array of the influences that we would be experiencing. Thats in a nutshell. The things i have done as a journalist is constantly write stories telling people to get flu vaccinations, but they really kind of suck. People always say to me, why should i get a flu vaccine . I would say 23 is better than 0 . As far as my mouth goes, that is true, but im wondering i wrote something for a report that many of you have access to, the vaccine report on influence and we put out last year, and i talked to literally dozens of people in this field, and not one person i asked them all this as good as we can do . At least one question. Is not one person said yes. Not one person said we are as close to doing it as we can do. Im curious, why are we so bad at protecting ourselves from what many people consider the sort of most likely virus to cause the most damage to humanity . I am going to let anyone of you who wants to answer this do so. Thanks, michael. I wish the narrative would have come up on the video coming through, because it was called a sense of urgency to address this problem. There are still 650,000 people around the world dying every year from seasonal influenza, and if we take the scenario that the Gates Foundation modeled, which says if we have another outbreak like we did today, we would have 33 Million People dead. Not only that, that virus would have been seeded all around the globe. And then we start releasing vaccines. We are still behind the gun on the tools we use to make the vaccines. We have reasonable vaccine foundations, and we can make them better by adding highdose vaccines that are not fully utilized. A lot of people across the world do not have access to the vaccines at all. I think the sense of urgency needs to be there, but also the fact that we need to leverage the tools we have and envision what that universal flu vaccine is in a very rapid, urgent pace to t there. For part of my life, i taught at stanford, and people use this word in Silicon Valley that i mostly hate, but im going to use it now disruption. Why dont we blow the system up . Obviously we cant turn off the spigot and say everyone in the world should get this new vaccine we have not given yet, but there must be some way that we grow vaccines mostly in eggs, the way we did in 1947. We live in a world where i can download whatever song i want onto my phone at command, and we grow vaccines the way we did 70 years ago. What is going on with that, peggy . I think i can talk on my own. I never knew that about you it certainly is the case that we are behind where we have to be in terms of the urgency of this threat and how we are harnessing advances in science and technology, and how we are mobilizing society to recognize the magnitude and scale of the problem before us. Clearly, disruption comes with uncertainty, and it comes with uncertainty on many levels uncertainty within the Scientific Community and how we do science, regulatory uncertainty, which i know something about, and also uncertainty about adoption and access and all of that. I think one of the things is, and i think hopefully one of the messages coming out of this panel is, its time to stop talking. Its time to act. We have talked about these issues for a very long time, and that has taken the place of action sometimes, i think. But in terms of why we are still growing it mainly in eggs, i think part of it is that its just the way weve always done it. Its the way we know we will get some kind of vaccine into the marketplace. And theres always the hope that in the meantime, other work will be going on and we will have the breakthrough and the aha moment clearly is not going to happen. It is also that we have not had the sense of urgency. Do we need to have lots of people die for that sense of urgency to occur . The incredible thing is lots of people do die every year, and yet we are not mobilizing. To be more positive, since i cant really answer the question of why it has taken us so long, because i think it shouldnt have, and there really is not a good excuse, the science has had to move forward. Gaps in the science bill persist, including our understandings of immune protection in addition to understanding the nature of this particular virus, which has its complexities. Certainly part of the problem has been that it is much safer for a company to just keep doing what its doing than trying to do something new. But also, we have not funded all the work that needs to be done. On an optimistic note, there is a lot going on, and tony is leading efforts, and there are of her efforts from the Gates Foundation, european research, horizon 2020. But we are also not collaborating, and that needs to be addressed. We needs just we need to start sharing knowledge. We need to identify where the gaps are, how we can fill those. We need to identify, what are the rats we are stuck in that we have to get out of, and how are we going to use all the capabilities of science and Technology Today and the energy of our society and the Scientific Community to get the job done . This collaboration issue seems particularly interesting and urgent to me, because there is a vast amount of data out there. A lot of it just falls by the wayside. If you do a study and it is not published, then it goes away. Yet there may be good data. I think casey has something to say about that, about openness and collaboration . Can you hear me . Yes. I dont need a mic. Good day. I think isolation is our enemy, and there are opportunities to expand transparency and expand a culture of transparency and open data sharing that i think could unlock breakthroughs and create new insights to accelerate our progress. We are the sole philanthropy on the group, and we really build into our dna a bravery about asking really hard questions. For example, we have been asking, what is the role that publication bias may play in limiting our progress going what are the opportunities for funders in this space to meaningfully collaborate, to build code funding opportunities and build strategies together . What are the ways by which there can be cohorts in a collaborative session and less as individual contributors . One of the programs i think michael is alluding to we established a new collaboration with the center for open science and the Public Library of science to really create new incentives for researchers to publish no and the negative null and negative findings. If we can shed more light on data that is not published, can we create new incentives to bring that those analyses to the front and shed more light on them . I think it would be wonderful. This new program we are starting, we are asking researchers to open the file drawers, pull out the floppy disks, whatever they have, and we will pay them to reduce that opportunity cost and to draft to those manuscripts and work and help them get those published because we think there are a number of opportunities ahead of us if we shed light on opportunities. Im curious, it is a pr issue in some ways. People talk about the flu i had the flu, i feel fluish, and 80 of that time, i am making that number up, they dont have a lot bit a lot of time. I had a bug. I wont call it the stomach flu, but most people would call it that. Is the problem we dont have appropriate nomenclature . There is complacency on that side, as well. Peggy mentioned the institutional architecture that keeps innovation from happening. I think those things are connected. People say the disease isnt so bad, i had the flu, i got over it. The vaccine isnt so great, fair enough, ill take it. There is that piece, as well. But the Vaccine Institute is in washington. Innovation is one of our pillars and we teamed up with aspen last year. The idea was a Diverse Group of thinkers, science, philanthropy, industry, journalism to take on issues in vaccination and not surprisingly, given the 100th anniversary of the 1918 pandemic, that was the issue. That is where the speech with video came from. But that is where the urgency came from, and the recognition is we need to do some things differently. There was a discussion about the cascade from communication to coordination to collaboration to convergence, and we need to work our way down the pipeline to make sure we are actually getting all the way to the end to bring in as much as possible to take on this problem. The complacency really israel. Reflecting back on when i was in government, not in the last administration but a few administrations back, and i was developing Public Health preparedness programs, and i went to fema to talk to them about doing a tabletop exercise around preparedness for biological threats and we were going to do a flu pandemic scenario and they said we dont do infectious disease. We do hurricanes, we do floods, earthquakes, all kinds of disasters, but disease outbreaks . I encouraged them to participate and it was incredible to watch them as events unfolded and realizing how much this kind of an outbreak would undermine all of the essentials of civic life, how it would undermine their own ability to mobilize and respond to needs, and also, the recognition of the Economic Costs and productivity costs in addition to the medical concerns and ultimately the loss of faith in people in government and leadership, because of the failure to be able to provide vaccine in a timely way and other things, so people still dont think enough about what this really means in our daily life and what the impact our, even though every year impacts are coming even though every year, we are suffering a lot of preventable deaths, illness, and disability. That is on why i asked the dark question, do something really that have to happen . It seems one of the curses of the Public Health world is if you guys do your job well, everyone goes along but if you dont or do your job well and people get sick anyway, somehow you just failed. Im not sure how you get around that. Id like to take a half step back and maybe tony is the person to address this, cor rick. Can you give a better sense of how far we have come on our approach to a universal vaccine in the last decade . We really didnt we didnt really have a real confidence in the scientific asus basis that we could produce a response or even what component of the virus, if you had an immune response would actually broadly cover. When we had the evolution of structure based vaccine design, when we used cryo ems to look at the molecular configuration of the stem, one of the big targets of a universal flu vaccine, certainly not the only target, but one of the targets if you look at the hemaglutin in molecules, if you metabolically construct it, it is like a head, which is a mushroom cap with a broccoli cap with a stalk. Part of the body the part the body makes an immune response against is the head. When it sees influenza, it much prefers to make a response against the head. When that gets it right, that is good news because you will get protected. The sobering news is that is the part that does the mutations i mentioned a bit ago. The stalk or the stem doesnt really change much at all. That is potentially good news. The challenging news is the body doesnt readily make an immune response against that because it is not immuno dominant and it hasnt been studied well. Now that we know that if, in fact, you make a response against the part of the virus that doesnt change, that when you look at the response body makes and test it against an array of viruses, you get a much broader coverage than against just that particular head of the hemagglutinin, which likes to change from season to season, whereas the stem stays the same relatively speaking. That is not something we knew 40 years ago. That is something that just now is beginning to appreciate. What investigators are doing and not the only target is to take the stem and get rid of the distracting head, and stabilize that stem and put it in a way, not growing it in eggs, not growing the virus at all, but getting the protein and sticking it on a self assembling nano particle that is much more immunogenic. You dont have to grow it, you can make a lot of it, and if you do it right and partner with industry, that is the kind of thing that doesnt have the vicissitude of growing an end. Egg. The critical challenge, and it relates to one of the things peggy said, is in order to make the transition from getting out of the tried and true egg growing, which we know gives us results that can be beneficial, weve done well with that, to something that has to be much better. You have to prove that this works, and then youve got to go through all of the clinical trials, phase one, phase two, phase three, and show this particular product is going to be good over a period of years. That alone if it works perfectly is going to take a decade. Im not a representative of the industry but ill pretend i am one. I make a flu vaccine every year and it protects people to the degree why the hell when i go spend 400 million to do this thing which may be great . That is where the federal government comes in. Seriously, what happens you bring up an excellent point. Our responsibility to the Public Health and not the profit line has to be able to push the process to the point where industry will find it to be a benefit to do that. If you sit back and the company that has been growing eggs for thirty years to spontaneously change without any incentives, it is not going to happen. Can i add . It is not that the field is not active. For 40 years or more, there have been concepts and approaches and it has eb and flowed, the amount of energy from biotech and from large pharma. In the 1980s and 1990s, the target had a lot of energy focused around there. Been funding became available from government in 2005 and 2006, so a lot of new ideas cropped up, but they were still focused on the framework that the government put out saying it should be an ha based antibody vexing. Dear vaccine. We have been learning so much about vaccines through the field that we have had a dogmatic approach that an antibody is the only thing that will save the day for influenza and now the resume of science from investigators, and studies showing how the breadth of an immune response is critical for so many of these lifelong or long durable vaccine or immuno responses. The energy now, trying to pull that into an influenza vaccine approach is out there, but what i think peggy said is we are seeing a lot of silent approaches, where there might be 40 different approaches on companies in the pipeline attempting a broadly reactive universal or crossreactive as very different labels are putting on it for funding primarily, they are kind of siloed. You dont see them leveraging the. Of knowledge weve of what we have learned. We are not conducting really large efficacy trials, understanding the details of the immune response. We are not comparing the new Tech Knowledge hes we are technologies against each other. Where redistributed 100 50 million doses in our country every year, we dont know how many people are getting vaccinated, how many are delivered to people, which doses they got, and what the outcomes were. We can learn how to improve our vaccine. There are opportunities today with wealth of data that has been created for years that is being ignored because it is not hold up into some larger brain trust for 40 Different Companies to leverage and make the best vaccine approach or even for us to determine which vaccines we have today are working or not. If we uncloaked the poorest performing vaccines on the marketplace today, it might be very revealing to tell us which technologies