Let's get started. I'm Sharon Burke. I'm a senior advisor here at New America, and I run a program on natural resource security and also a new project called the Phase Zero project. But today I'm happy to be here on behalf of my colleagues at Future Tense, Andreas Martinez this year. He's the director of that. Future Tense is a great program. It's a partnership between New America, ASU, and Slate Magazine, and it explores emerging technologies and their transformative effects on society, and especially on public policy. Future Tense does this in a variety of ways, but most importantly through terrific public events here in New York City and Arizona, and also I should make sure that everybody here realizes that not only do they do these public events with an in-person audience, they have a considerable live stream audience. And anybody who's joining us through those means, you can follow the conversation with hashtag, water will come. You can also follow Future Tense on Twitter at future tense now. And a couple of housekeeping items, if you haven't already silenced your cell phone, please do that. I will publicly shame anybody whose phone rings, unless it's a really good ringtone. And then also during the Q&A, do make sure that you wait until the microphone gets to you, because as I said, we usually have hundreds of people joining us online, and if you jump the gun on your question, they will not hear your question. So wait for the microphone. And you're very fortunate today and that the author we're here to talk to will stick around and sign copies of his book afterwards if you stick around and buy a book, which I would encourage you to do. So with that, let me introduce our two speakers. Right next to me is Man of the Hour. This is Jeff Goodell. Jeff was a class of 2016 and 2017 New America Fellow, most importantly, aside from everything else he's done. But he's also currently a contributing editor to Rolling Stone Magazine, which is also pretty impressive, I guess. This book that's just coming out today, right? Today's the day it's coming out. It's called The Water Will Come, Rising Seas, Sinking Cities, and the Remaking of the Civilized World. This is not Jeff's first time at this particular rodeo. He's written many books, award-winning books, terrific books, geoengineering. I have to actually look at the whole title, but I certainly remember what it was about. How to Cool the Planet, geoengineering and the audacious quest to fix the Earth's climate. He wrote about Silicon Valley. He's written about Big Cole. So this is a great thinker in our cultural life in this country, and we're very, very delighted to have him here today to talk about this book. And then we have Senator Sheldon Whitehouse. So if you don't know who Senator Whitehouse is, you need to know, and you're so lucky you're going to get to find out today, because he's not only a courageous voice for Democrats, for all Americans, for governance, for good governance, for Rhode Island. He's also a passionate voice on climate change and on climate security, which is where I know him in particular. He has a number of committee assignments. The one that's particularly important today is that he's the ranking member on the Committee on Environment and Public Works. But he's on the Budget Committee. He's on the Judiciary Committee, which I think reflects your background as a lawmaker in Rhode Island and in the nation's capital. So we're delighted to have him here today as both a voice of reason in our government at the moment, but also particularly on this issue. So Jeff, let me start, as you can see, I have lots of comments on your book, and they're vaguely color-coded, but at some point that became beside the point. You know, one of my first questions for you about this book is almost, what would you classify that as? What genre? Part travel log, part science story. It's a lot of narrative stories. How would you describe what kind of book this is? That's a very good question. I think of it as a sort of exercise of my kind of tragic imagination. Okay. You know, I had been thinking about and writing about climate change for a long time and knew about sea level rise. I'd read the studies.  And I was very familiar with all this. And then Hurricane Sandy hit. And I wasn't in New York at that moment. I went there a couple of days later and I saw the Lower East Side and I saw the nine-foot storm surge that had come in. And I was like, wow, it really was visceral for me in a way that other things had not been. And I was talking to some scientists. And one of the scientists at Columbia said, one way to think about this, Jeff, is as a kind of dress rehearsal for sea level rise. Because imagine this nine-foot storm surge comes in and it doesn't go away. I mean, with Sandy, it was there for two hours, three hours, and it recedes. And sea level rise, think about what the world would look like if you have that water like that. And so I kind of did. And they took up that challenge. And I thought about it. And I thought about it for another three days and talked to more people. And they said, well, if you're really gonna think about this, you gotta go to Miami. And so I went to Miami. And I thought about it there for about another three days. And I mean, it was just very apparent that the risks in what this world was sort of facing with in the future was sea level rise. It was something that no one had really been thinking about in any real way. Because it became clear to me that Miami was not gonna make it in any kind of real scenario of anything like five or six feet of sea level rise that we're talking about to be at the end of the century or more. And so I just thought, wow, this is a great American city that basically is tragically kind of doomed for the future. And I need to write about that. And what does that mean? What does it mean to a great city? How will a city like this adapt? What will happen as the water comes in? And just, that's where I started. And Miami is almost a leitmotif all throughout the book. You come back to it. It's sort of the guideposts as you tour the world. So tell us exactly how screwed is Miami and why? What's the history here? And when is this gonna happen? Is it already happening? Well, it depends on your definition of screwed, but... Are you a writer? I mean, I would say that, I've thought about this for a long time and I don't see any kind of scenario in which Miami, as we know it today, the Miami that, as we think of it, kind of exists by the end of the century. I mean, and that's mind-boggling to say and I realize it sounds really kind of nutty, but it's not. Because Miami is a particularly difficult situation because vast majority of it is less than six feet above sea level. It's built on a kind of porous limestone plateau so that unlike, say, New York or other places, many other places, you can build seawalls and potentially hold back the waters for some time as the waters rise and you can build the walls higher and higher and there's problems with that, but at least it's a defense mechanism. There really isn't a defense mechanism for Miami. I mean, people talk about putting like this sort of giant, sort of kind of epoxy thing underneath the entire base of Miami Beach and the coast of Miami, which is, of course. I mean, there's all kinds of really nutty technological fixes out there, but so what's gonna happen is, as the senators, we've been in Miami together and we've stood in Fort Lauderdale and watched the water come up right into the streets of Fort Lauderdale. We are there at King Tide together. And this is not during a storm or other events. No, this is just an October day with the King Tides. And so, one of the things that really is important to kind of get about this and why Miami's in so much trouble and Southern Florida in general and other places, but that's really the poster child, is that it doesn't take like six or eight feet. You don't have to wait till there's sharks swimming through the lobby of hotels for it to be a problem. The problem is that the costs of a continued beach erosion, a road erosion, buildings being eroded, and washed out and flooded, the sort of economic costs of trying to sort of patch all these things. In Miami right now, they're spending $500 million to build pumps and try to elevate some of the city, a couple of feet up. And that's fine, but it's 500 million bucks and you've elevated like 12 blocks for two feet and that will help a little bit. So you can do things to buy time. But eventually, the costs of doing this, of trying to keep up with this are so huge. And especially if we get into scenarios which are certainly possible, not probable, but possible of dramatic impulses of sea level rise where we could get a foot or two in a decade or a decade and a half, that's possible. And if that kind of thing happens, of course, that's it. And you talk to a lot of people in Miami. So all the places in your book you went to and you talk to people. And I think at one point in the book, you described it as people are going through the stages of grief. So where do you think Miami is in that process? They're just coming out of the denial moment. There's a powerful impulse for denial in Miami and in South Florida in general because the engine of the economy is basically real estate development.  How's that gonna work? So once the reality of this starts being factored in, it's a pretty scary scenario because there's no state income tax. You have a governor who is basically banned saying the words climate change from any kind of government. He's like a pioneering denier. So you have this political infrastructure there as well as the sort of economic infrastructure that is all committed to sort of saddest quo. And so people who got most in my face in Miami when I was reporting this were the real estate industry that realtors and accusing me of trying to destroy Southern Florida and Miami and why do I hate Miami so much to talk about this? And they were worse than, I mean in the sense of being worse and in the sense of being more aggressive than I spent a couple of years in coal country reporting on the coal industry and the real estate agents in Miami are more fearsome coal miners in West Virginia. Well, and it's even though Miami is a theme that runs throughout the book and you come back to it several times, it's also a parapetetic book. Literally, you're going all over the world but you're also hitting all the key issues in climate change and what's happening right now but I wrote down some of the cities you go to. Venice, Rotterdam, London, New York City, Marshall Islands, not just a city but a whole country.   You mean climate change? You mean how people think about climate change? You know, I think that it's pretty consistent that the more of a sort of vested interest you have in the status quo as in like the more expensive real estate you own on the coast and the more at risk, the more libel you are to be in denial about it and so the places that are at least within denial about it and the most embracing of the changes were places like Lagos where I went into these water slums and people live on- You explain what a water slum is. Yeah, so there's a, you know, Lagos is a city in Nigeria that is, no one knows exactly how many people live there. It's possible to count but the numbers range from 13 to 20 million people and a lot of people have migrated into Lagos from the outlying parts of the country and they've just sort of created these water slums. They've just gone out into the lagoon that is on the interior of Lagos and built houses in the water on stilts essentially and they're essentially kind of squatters but they've been squatting there for, you know, 100 years or so, a long time and there are these immense communities. They're like, you know, a kind of poor version of Venice. Hundreds of thousands of people living on the water and it was a really remarkable place for me to go because first of all, they were like very happy people. It was like they liked their life on the water. They fished, you know, they built these houses and, you know, I talked to them about climate change and sea level rise and storm surges and they're like, yeah, so what? So we'll build our stilts a little bit higher and, you know, it's great, you know, we don't, we're not worried about that at all and it really underscores the fact that what the real problem here is that we have this huge amount of infrastructure that are built with this idea that the line between land and sea never changes, you know, that somehow that this is a sort of stationary thing and one of the profound lessons that I learned in this is that that is so not true. Obviously sea level rise has risen and fallen over time. We're pushing that faster now, exhilarating that and in addition to that, you know, things like beaches, you know, are like mobile devices. They're like, you know, they move all the time and we try to make them stationary because we have an economy, especially in places like Miami, but in matter banks and many places where beaches are a key part. People don't come to the shore to lay on, you know, a crag of limestone. They come to lay on a nice beach. So there's a lot of money put into keeping these beaches in place, which is gonna be more and more difficult. But just let me say one more thing just to turn this one more about the Lagos in Miami connection is that I said that Miami, you know, is, I can't see a vision of it the way Miami we know today is surviving. But I do think that it's really important to underscore that I think that there's gonna be a lot of creativity in how we live with water and how this is gonna force us to rethink and to think about things like floating cities, floating platforms, canals, all kinds of ways of living with water that we haven't thought about because we haven't had to or because we haven't realized the sort of risks that we're facing. But I do actually think that, you know, along with all the flooding and destruction and economic problems we're just gonna create, I also think it's going to create, you know, some wonderful new places. People love living, I love living by the water.    We're gonna keep talking about the book, but I do wanna bring the senator in also. And there's also, I'm gonna give you something to think about and then I wanna ask the senator a couple of questions. This book is entertaining, it's funny. You have some great stories in here and some really rich language and I would love to share some quotes with people to wet their appetite for the book, but I do wanna read how you end it because you strike me in the time that I've gotten to know you as an upbeat and optimistic guy and I think anybody with kids has to be thinking about the future and that is the nature of this program, so that's fine. This is the last paragraph in your book, but mostly the city will be forgotten, one of many places lost to the attacking sea and some distant future, someone or some human-like machines may explore the sunken city and find bowling balls, stainless steel knives, gold wedding bands, and ceramic tiles. They may wonder about the people who lived there, what their lives were like and what they were thinking as their world went under. So you don't exactly end on an optimistic note, so think about that for a minute and let's talk about that. But I think one of the things that's, yeah, but I think, we'll come back to that in a minute especially because you do talk a lot about various solutions and my question on that is, is this really an anti-adaptation book as an area of focus? Think about that. One thing that's true throughout the book is that our ability to govern through these kinds of challenges is weak, worldwide, but certainly in this country and our capacity as a polity to approach these issues in a credible and realistic way is just nothing, it's so weak. And one of the questions I had for you, Senator Whitehouse, is I know you've written your own book about that, a very good book, and you've talked about it passionately, but I also wanna ask why? Why you have taken this on? I looked up the demographics of Rhode Island and it's down the middle, it's a median household income of about $58,000 which is right at what the national average is. 86% of the population I think is white which is above the national average. Most people have only a high school degree. It's not like Rhode Island is an elitist paradise of people who believe in climate change. You have the same population the rest of the country does. So why are you able to be an advocate for this and other senators are awfully quiet or actually against doing anything on this topic or against the science? Well, Rhode Island has a very different geography. Then the rest of the country does. We are the ocean state and we have a lot of waterfront along our South County coast, up through Narragansett Bay and up along the shores of Portsmouth and Tiberton, Little Compton, Aquedic Island is a big island right in the middle. So everywhere you, there are a lot of places in Rhode Island that are very close to the shore. And we're being warned by NOAA, by our Coastal Resources Management Council and by the University of Rhode Island that by the end of the century we're gonna have nine vertical feet of sea level rise and you can do the map. And when you do the map and you look at the before and after, I don't want it to be on my watch that the decisions were made that made that damage and that removal of so much valuable property from our very small state, inevitable. And it's not that hard to foresee this happening. It also doesn't hurt that I'm married to a marine scientist and so the scientific facts of this are not very disputable. I realize you're ducking my attempt to call you out as a political hero, but Houston is in Texas so I don't hear any of the politicians in Texas being saying what you just said, Florida. Large parts of Florida are at imminent risk. Okay, well look. We don't hear. Why you? We have a fundamental defect. Why not everyone else? We have a fundamental defect in our political system right now. It is primarily the fact that we did not respond appropriately to the I think very erroneous and mischievous Citizens United decision. The result of that has been that unlimited money can now be spent in politics by big special interests. And because there hasn't been good cleanup, unlimited money can now be spent anonymously in politics by special interests. And if you think there's something worse than unlimited special interest money in politics, try unlimited special interest money in politics that nobody knows where it came from. That's where we are right now. And I think it's gonna be a lasting disgrace that we didn't fix that decision or fix the dark money problem that relate to it. But that is the fundamental reason why we are incapacitated in doing this. It is not that there is some partisan disagreement. It's that a very big industry got brand new political artillery, went to the Republican Party and says, anybody in this party that crosses us on this is dead.  And there are an awful lot of Republicans who are waiting for the weather to clear so they can do what they know is the right thing to do but the weather is not really clearing. So I don't have the problem of a big home state fossil fuel industry. I have a problem of a home state that really depends on fishing and coasts and things like that. In that sense it's easy for me to take them on. But I also have a sense of, I take offense that the democracy that people bled, fought and died for generations to build and preserve now gets to be taken over so easily by this particularly noxious industry and it's particularly bad behavior. How do we get out of this? Transparency in political spending would be an opening bid because my guess is that three quarters of the unlimited money in politics would go away if it wasn't dark money. We are going to get out of this. We're gonna get out of this to follow Jeff's point when it becomes clear to real estate agents that properties that they wanted to sell are unsellable. Insurance agents that they can't insure properties, community banks that they can't put a mortgage on properties and coastal property owners that the property that they had invested their time and their money and their effort and their emotions and their family vacations and everything into now have negative value because the present value of all the flood insurance exceeds the value of the home. They can't sell it, they can't mortgage against it, they can't do anything with it. And that, when that shock comes, is going to be a very, very powerful shock and I think then people are gonna look around and say, how the hell did we get into this? And there's gonna be a very direct finger of blame to point at the fossil fuel industry and all of its front groups which have propagated one of the biggest scams in modern political history. You think about that? I think that's exactly right.  But of course, like all these kinds of things, by that time has already been so much, you know, most of us know carbon dioxide stays in the atmosphere, you know, hundreds and thousands, parts of the hundreds, parts of the thousands of years. It's not like other kinds of pollution where you stop the emitting and it falls out of the sky. So we're sort of front loading all of this stuff now. Oh, by the way, it's not just us saying this. If you look at Freddie Mac, which is the ginormous federal agency that backs residential mortgages, they've said very plainly that the coming property collapse along our coasts is gonna be worse than the mortgage crisis and the Great Recession and they've been backed in that by industry publications like the Risk and Insurance Journal, which looks at this stuff. So this is not just, you know, an author and a senator saying this. These are the people who understand the mortgage and risk industry firsthand. So they're warning us, here it comes. Is the moment here? I mean, granted, what just happened? Getting very, very close. With the start can season? I mean, we heard in an event here a couple of weeks ago from our partners at Florida International University that, I mean, this was a near miss from Miami. It wasn't even a direct hit, but that they're gonna have a very hard time with recovery. We heard that in Houston that one of our guests works with insurance companies. She said 90% of the early estimations of damages are from floods, not wind, which means the National Flood Insurance Program has to cover it, which is already. If they had national flood insurance policies. If they had it. And many did not because those maps aren't accurate. And even if they did, Senator, that, and you write about the program as well, it's not, it's a program that was well intended but hasn't had great results. And, but it's something that everyone in the Senate knows is a problem that no one can fix. Is that gonna continue to be the case? Well, we're gonna have to reauthorize it. We just poured huge buckets of money into it in the bill that's pending before us now to forgive the debt and tee it up for the next round. But, as Jeff said earlier, this is a program that presumes a stable boundary between land and sea. And that presumes that a 500 year storm is a 500 year storm. If a 500 year storm becomes a five year storm and the border between land and sea is mobile, then you've gotta rethink that program quite a lot because you can't simply pay to have people rebuild and rebuild and rebuild and rebuild in the same place. And how you manage that transition is a big problem for us to face in Congress. You see this as a coming federal crisis? It is gonna pit states against each other, it already does. Yeah, well, we got a lot of landlocked states that say this is just a big subsidy for you coastal people. And then I think we say, yeah, well, how about crop insurance? So everybody's got their own thing. And frankly, to the extent that this turns into a regional dispute, a geographic dispute, that actually might be a lot healthier than the current lockdown of the Republican Party by this massive fossil fuel special interest. If we could break that dynamic, the geographic dynamic is one that the Senate has faced for generations and it usually operates reasonably well. It's a peculiarity in our history that we have this circumstance in which one party has been basically bullied and forced into becoming deniers of something that is virtually self-evident to the world at this point. Do you see any change in that? We've heard that there's some new. The pressure is boiling. And I think a lot of people felt they had cover when the Obama administration was gonna do things to fix this anyway and they could theatrically be dragged behind the wagon, complaining about it as they went. But once the wagon has actually stopped and you own responsibilities for nothing and exactly and it even might be going backwards, suddenly you've got to rethink. Particularly if you think you might be around for six or 12 years and you think ahead to, okay, what's this issue gonna look like to the American public in 2026? What's it gonna look like to the American public in 2030? You start looking at what it's gonna look like then and you dial back to what you're saying now, not a great place to be. You know, we're doing a project here on severe weather in the United States and one thing we found is that you only really get action after a crisis but that people also have short memories for severe weather. I mean, these storms all happened, Maria, Irma, Harvey, after you finished the book. You think this is gonna be a catalyst moment or just something that people forget about quickly? Puerto Rico won't forget. In fact, it's more of a danger that Puerto Rico gets forgotten but are you optimistic at all that this is a moment? No, I was on stress area today and you'll be on today and Harry asked me the exact same question and because it's a good question. It's like what will be the thing, right? And I didn't tell her this, so I forgot. I didn't, I just wasn't, I had not had enough sleep so I didn't remember this. But I remember when I first started writing about climate change, I went out from Woods Hole with some climate scientists for a month-long cruise in the North Atlantic and it was a really great thing for me because I was just learning about climate change and I had a lot of questions and we would sit out on the fan tail with a bottle of bourbon and look at the stars and talk for hours about everything, from bioluminescence to, you know, just everything. And I remember asking this really growing in scientists at the time, what is it gonna, what's gonna change, you know, people, because he was already like saying that the science, it's far worse than the scientists were telling me, you know, that we know more than we can really say kind of thing about the risks. And I said, so what's gonna change? And he said, well, when a big storm comes and wipes it out in American city, I think that will wake people up. And of course, you know, we had Katrina, Sandy, I mean, it's just, I think this notion that some traumatic event is going to wake people up, I don't see evidence of that. You know, I think that it's a slow progression. I think it's about, I mean, I do think people who experience it, who see it, have a different feeling about it. You know, there are Republicans in South Florida who understand that climate change is real and are willing to speak about that. But, you know, I don't know about this sort of transformative event thing. I just, you know, I don't know, it's skeptical. You talk a lot in the book about the various ways people are trying to deal, and particularly engineering solutions. Could you talk about a couple of them, like Moe's or Big U or some of these projects that you visited and what people are trying to do? Well, I mean, one of the things about Sea Level Rise and about the problems that cities face is that every city is different. The situation that they have to deal with is different because of the coast, the shape of the coastline, the geology, the population, all the money, all kinds of things. So, but the, you know, sort of basic fundamental question is about walls and do you build walls? Because Sea Level Rise is really a problem of elevation, right? If you're high enough, it's not a problem. It's so a wall is a way of kind of building elevation. So, for a lot of places, Lower Manhattan is the great example.  Most valuable real estate in the world. You're not going to move Wall Street from Lower Manhattan.  So, you know, the idea of spending, as they're planning now, they don't have an exact number, but three, four, five, six billion dollars to build this thing called the Big U, which basically goes from 50 or 48 street on both sides, all the way around Lower Manhattan.  Yeah, I mean, it's like, it's a downtown Manhattan kind of wall. So, you know, that's a no-brainer. Of course they're gonna do that. There's no, it's not even any, there's no other way to think about it, really. But then you have places like Venice is really fascinating because Venice is obviously, I mean, I went there, I've been there a number of times, but I went there for this, and I loved it so much, partly because I saw the sort of tragedy of it. I was sitting in like Piazza San Marco, like in first day, and the water just starts running into Piazza San Marco.  It's like no big deal, it just happens all the time. And you really get the sense of a sinking city. But so they have decided that they want to build a wall also. But being, because they're Italians and it's a Venice, you know, can't be a wall, it has to be this thing that recedes and goes down so you don't see it. One engineer there calls it the Ferrari on the seafloor that goes down in Venice on a lagoon. And this thing goes down until you have high tides or big surges and then it floats up and cuts it off from the sea and protects the city. The problem is that they've been engineering this for 25 years and planning on it. And, you know, at 25 years ago, no one was thinking about sea level rise or at least certainly not the degree that we are. And so this thing is going to cost four billion plus a billion and a half for ski condos for all the contractors and government officials, 500 of which were arrested for the corruption of this project. So they're gonna spend, you know, six billion dollars of public money or so for something that's engineered for 18 inches of sea level rise, which is, you know, nothing. And so this problem of how do you build engineering infrastructure at a time when you don't know, if we could say, oh, in 2100 it's gonna be two feet or three feet, then okay, here's how we do that. Here's what we're, it's worth it to spend this much for this long a time. But we don't know that. We don't know if it's gonna be two feet. I think it's gonna be, personally, it's gonna be six or seven feet or more and it's gonna keep going after that. And so then what do you do? So this sort of engineering uncertainty is what's really hard. And there's ways of dealing with that. There's ways of thinking about that. Doing engineering project in stages. They're doing a pretty good job of that in London, around the 10th, Newbury or there. But it's a real big challenge. And ultimately, this is not a complicated story. The simple story here is two things have to happen. One, rack will cut into missions, as you've talked about. The other thing is retreat. So there's gonna be- Explain what you mean by that. Well, there's gonna be tons and tons of, or billions and billions of dollars wasted in coastal adaptation that is not going to last for very long. Or it's just gonna be buying time, or it's not gonna work, like I would argue, this Venice Wall is just six billion dollars, basically. There's other ways they could have done this that wouldn't have cost that much. There's just gonna be a lot of money spent on things that are only gonna buy time for a short amount of time. And the real solution to this is to move to higher ground. That's really what's gonna be the sort of economic solution to this. That's the smart solution. It's just how do you plan that? How do you, what kind of tools do you use, whether it's in zoning or taxes or various kinds of investments to encourage people to move to higher ground? And make this risk transparent to people. You mentioned transparency. I think everything that can be done to make this risk transparent to people so they can make their own decisions and begin moving. But the hard thing is moving big public infrastructure, like New York, the Subways, how do you deal with that? Miami's airport, many airports are right on the water, Boston. How do you deal with that? You can raise them a little bit, but it's the same problem with Norfolk Naval Station. It's like you can protect the base, but how do you protect the fact that 75,000 people need to get to the base and you have roads and all that kind of thing. So how do you protect the area around us? You can raise the elevation of a runway, but if you can't get there because the roads are flooded, that's a big problem. In fact, you say at one point, and Senator, I want to throw this one to you. In the book you say, this is how disaster relief works in America. There are lots of incentives to rebuild, but few incentives to rebuild differently. How do we change the incentive structure? Because what Jeff is saying about, we need to retreat and we need to stop burning fossil fuels. How doable is that? Changing the incentive structure is something that already began to happen in the Sandy Relief package. And much more investigative and research work was funded by that than just clean rebuild and much more flexibility in how you rebuild and how you rebuild sustainably and how you rebuild in a survivable way was allowed. So we have a considerable repertoire of experience with that that I think will inform our next go rounds as we look more and more at this. So I think there'll be less of the problem of, unless you build the exact same thing, exactly where it was, we're not gonna fund it. I think we've beaten that. It doesn't help us address the larger problem of what happens when it really isn't rebuildable reasonably and how do you compensate that person and should you compensate that person and to what degree? All of those questions are still pretty vague and of course the larger question of how you stop the carbon dioxide emissions is the race that we are in because the folks who are profiting from the carbon dioxide emissions are very interested in not having the transparency about what's coming because they don't want action. They want to continue to do their thing. So that's the real hard part to try to solve. Let's talk more about that. But I'm more optimistic than Jeff. I think we can. Why are you optimistic? Because I have got a lot of... Did you read his book yet? I have a, yeah, yeah I did. I have a lot of conversations with Republican colleagues who are ready to do something who are interested in doing something who encourage me to keep making noise who agree that a carbon price is the way to go about this and they're like looking for the way to get there. It's like talking to prisoners about escape. They want out. They know that it's a hell of a dangerous fence to try to get across because of the fossil fuel attacks that they can see through all the front groups and everything. But on the other side, we've got a pretty strong agreement about what the right solution is which is a revenue neutral border adjustable price on carbon. Yes, okay, good. So this is actually quite a solvable problem in that sense and there's considerable motivation within the Republican caucus to try to get there. The problem purely in my view is the political force of the fossil fuel industry and its front groups that continues to be brought to bear on this. If you've heard that the CEOs of Chevron, Exxon, Mobile and Shell have all said climate change is real. We're causing it and we think a carbon price is a good solution. Don't believe them because that word has not gotten to any of their lobbying and political operation. Their lobbying and political operation is still entirely at cross us and you're dead. And I kind of doubt that their lobbying and political operation is operating independently of those CEOs. So I think this is just more of the dissimulation that they've been famous for. So it is, I mean there's a lot of major oil companies now that are saying that. And it's great that they feel that they need to say that. I just wish they were actually treating it as true and instructing their political forces. Okay guys, it's over. Let's get a deal and let's get something done here. So you think a carbon tax is politically feasible? Yep. Would it come through the budget committee? No, it would come through the finance committee most likely and conceivably with some elements from environment public works. But a bipartisan budget, if we could ever do one, could tee up an enterprise like this. Frankly, as it is the way they've teed themselves up for tax reform, this could be a part of tax reform when they get around to it. They find that they're in another blind alley and they can't get out of it and they need a way. You'll offer them a way. We've got it. Okay. What about, I mean one of the things that's really hard about this is that our economy and the global economy does run on fossil fuels. It's about what 89, 90% of current primary consumption is fossil fuels. So that's a monumental task. Are you optimistic about the technologies available to improve efficiency and substitute other kinds of energy generation? Very. When you look at places like Iowa, which not only has more than 30% of its power coming from wind, it's investing huge amounts more so that number is going to be driven way further up and telling me the grid operator for Iowa has been able to figure out that this is in fact baseload power. You just need the right algorithms to figure out where it comes from and when but you can treat a significant portion of it as baseload power. So the argument that oh if you buy wind it doesn't help because you still have to have the coal plant for when the wind doesn't blow is just a falsehood as demonstrated by the people who actually run the grid there and solar is picking up in the same way. The technologies of battery allow solar to become baseload itself. You can get a much more individualized off the grid approach for a lot of people and the prices of solar and wind continue to go down and they're already past a crossing point with coal and they're on their way to a crossing point with all fossil fuel and you put those two things together and suddenly you have like the digital revolution that's just happened with clean energy and it can happen very, very fast. You have I think in Rhode Island the first offshore wind. We do. And you know what made that happen? It had nothing to do with anything else other than that the regulatory setup had always been fatal to offshore wind proposals and some very smart people in Rhode Island figured out how to redo the regulatory piece so that it became manageable for the developer and we cut no corners but we made it sensible, smart, compact and congruent, coherent. And they got through it and they're in the water as a result. So they're these kind of weird externalities like not having figured out how to do the regulation right of the sighting that prevents something really good from happening. All those things can fall away and that enormously expedites these technologies. We're doing something, we're developing a common app for every one of Rhode Island's little towns so that if you're installing residential solar you have the same application no matter where you go. So you don't have to become an expert in how Coventry or East Greenwich or Burlville or Portsmouth license the stuff and what you have to do to get through them to get the approval, it's boom. So if you're the installer and you went from a three day process of trying to figure out the permit to a one hour process, you just really dropped the price and the availability of solar. So there are lots of things like that that are going on parallel to the technical lowering of the cost of solar and that all is just headed one way only and that is very, thank God for that. I wanna ask you a couple of other things before we give the audience a chance to ask questions and make comments. You have a lot of stories in the book about individuals like the senator who are, I don't know if they're your heroes of the story but you have several people throughout like Klaus Jacob, Tony DeBrum, Lowell Wood. There are a couple of people, I'm not sure Lowell Wood would be a hero, but that's more he's the inventor of a dangerous idea, I think we call it a dangerous idea, which is geoengineering, a different kind of engineering solution that's not destined to work. At least I don't think so. But maybe Klaus or other people who are like the senator, you have a couple of people whose stories you tell that you think are instrumental to how we're gonna change this. Don't take the bait on me. He's sitting right here. Yeah. You know, when I think about that, I think of a geologist in Florida that I met named Hal Juanlis, who doesn't make as, he's not as big, he's in introduction. And he's just this geologist in the University of Miami who goes around in South Florida giving this sort of blunt talk about what's happening. He's like in your speed dating scenario. Right? Yeah, right. And he's just like people like me and like the senator and like almost everybody in this conversation think about how do we talk about this in a way that is most effective to communicate and all that. And he's just like totally blunt. He's just like this Old Testament voice of the water. That's why the title didn't come from him. He didn't give me the title, but the title is his tone. I can just imagine him saying the water will come and you know this is like boom. It's like I don't, this is what science says. I'm not here to like soft pedal this and I really respected that because he just goes around and he's like tell me where I'm wrong and he's not wrong and it's just this sort of, I think that a lot of us get so caught up in the messaging and thinking about this and the politics that we forget to just sort of tell the truth. And not that we don't tell the truth, but you know what I mean? So for me, that was very inspiring. He was a very inspiring person because I just respected that about him so much.  You know, the people I met in Legos who were living in this unbelievably, you know, when I went to Legos and going through this water slum it's like we got into these hand dug out canoes, you know, what we rented for like 30 cents and I was with these two Nigerian guys who were my guides and one of them was like 350 pounds and we got into the canoe and the canoe is immediately just like this and as soon as he moves in one direction or the other, you know, the whole boat is about to go over and I'm like oh my God and then I see like little dead piglets floating in the water and I'm like please don't let me go in this water. But meeting the people there and going into that community were some of the people who, you know, it really gave me, they have these wonderful lives, you know, unimaginably poor but very connected to their family but also very like in tune with where they live, you know, they weren't caught up in like whether the water was rising or not and it really gave me a sense of like how inflexible we have become and how we think about how we live. Like we can't imagine modern life existing in any other way than the way we have it but in fact, I think there are lots of ways to imagine a wonderful sort of modern life and one of the challenges that we have now is to rethink that and to think differently about that and to imagine wonderful scenarios where we can deal with these problems and we're not building strip malls on the beach, you know, that are gonna be flooded. So those were sort of two moments for me. It is, I mean, throughout the human history how we've generally dealt with changing weather patterns is to move. Yeah, we move. Yeah, it's the same thing like you're on the beach laying on your towel with high tide comes up, you get up, you move your towel back. It's like, that's basically what's happening here. You also have a chapter in here about the military which is of course where what my background is and when you talk about telling the truth, I thought you did a really nice job because I think a lot of us will point to the half full side of the glass when it comes to the military and that there are people in uniform and veterans who will talk about climate change and the way that it affects security but you also make it clear that there's a lot they're not talking about but you talk in particular about the military as a landowner. So what, 28 million acres worldwide, a lot of it is coastal or in arid places or in Alaska. You wanna talk a little bit about, because you went to Norfolk and you already mentioned Norfolk once with Secretary Kerry and I know that Senator Whitehouse has also been to a lot of military bases and talked to people about these issues as well. I thought, again, I thought you did a really good job of being positive but also telling the truth. Well, the military is in a tough spot, right? Because as one naval commander said to me, we deal with the world as it is, not as we wish it to be. They are very concerned, so they see this, not only do they see this at places like Norfolk Naval Base but as you know in the studies about how droughts and famines are causing political instability and the increasing hurricanes and things like that getting them involved in various kinds of rescue operations, even things like Northwest Passage opening up and have ships going up there and what happens in one of these ocean liners that's going up there, hits an iceberg and goes down and who's gonna rescue them? And so they're thinking about this in all kinds of logistical ways that is very much about there, we have a job to do and this is a factor and we see it and we're dealing with it. The thing that I tried to capture in the book is the political bind that they're in, that I don't know of course as you know and Senator knows is that these people that I'm talking about who understand what's going on, it's not the entire, not everybody in the military, I certainly talked to some Marine commanders and things who were like climate change and it's like enough time for that. But in general, I think in my experience is that they're very knowledgeable about and aware of what's going on. But they can't talk about it because the example I use in my book is that at the Norfolk base they built a couple of new piers which were millions of dollars, they're enormous piers, they're giant concrete things for aircraft carriers and they elevated them four or five, six feet, these new ones and I said, did you do that for sea level rise? And basically the commander said yes, but we couldn't say that because if we would have said that then we would have gotten zeroed out by budgets in Congress, Republicans. And so they have to like do this sort of double talk where they do things that will help them in adapting and dealing with these problems and changing the way they do business basically without talking about it because it's politically too volatile to talk about. And it's really an untenable situation because at a certain point, large decisions are going to have to be made like where do you go with these bases? And it's not just Norfolk, there's a number of bases all around. You know, this is, I mentioned earlier, the problem of thinking long term because these large infrastructure questions are hugely important. And you know, closing or moving a military base is already like the most fraught political conversation you could possibly have. And so if physics are demanding it, if you have a base like Norfolk where the people can't get to the base, what do you do? I mean, you have to have this discussion in some way. And so it's like that moment is going to come and it's going to be really messy. I think the role of the military as a landowner has been pretty well documented in this area. The role of the military as an operator and trainer of people has also been quite well documented. And the role of the military as a military force in dealing with conflict, with climate change being a significant catalyst for conflict around the world. All of that has, I think, been fairly well documented in the QDRs and so forth, quadrennial defense reviews. And it's going to be even better documented in response to the language that we got into the National Defense Authorization Bill just now, requiring them to report on all that. The piece that has not been touched on enough, I don't think, is the question of America's reputational interest and our soft power. I think we've been kind of surfing on a wave of international goodwill launched originally by the Marshall Plan, rebuilding Europe after World War II and what we rebuilt in Japan. I guess you called it the MacArthur Plan after World War II and the fact that we're pretty good at not taking places when we go there and we tend to leave freedom behind us. So we've had this really, really good reputation and we hold ourselves forth as a city on a hill. What do we get for all of that? I think we get quite a lot. Come from a diplomat family and I think we get quite a lot. How do you equate America's example in the world as a city on a hill with having our vaunted democracy, having completely failed with respect to climate change for decade after decade in what historians will very clearly attribute to a failure of corruption of that democracy by a big special interest. That's not a great story for us to have to tell against the stories that the Chinese or the Russians or the Islamists or whomever else, they have counter narratives. Your rivals get their arguments and I think we've got to think about this issue in those terms as well. What does it mean for America's reputational power? What Bill Clinton called the power of our example, which has always mattered more than any example of our power. And you've got some passages in the book about that that would not only underscore what the senator is saying but are indicating that we're headed for trouble. You talk about the Paris Accords and some of the controversies there. This is coming. Yeah, you mean in the... Well, you have a whole chapter on climate apartheid, I believe, and talk about the Marshall Islands and that these countries are aware that they're on the short end of this and that they're not gonna, that the negotiations over loss and damage or reparations on some level for being the victims of climate change are not going anywhere. Well, and not only is the heart of the Paris negotiations what the rich nations of the West that have basically caused the problem owe to the people of the Marshall Islands or other places that have done nothing to cause the problem and they're bearing the worst of the burden. And that's the central fight or disagree or negotiating point in this. But it's not only, you don't have to go that far. I mean, I just came back from Alaska two days ago.  And, you know... And it's expensive. It's $100 million for one village of like 300 people. And there's, you know, they tell me 85% of the Alaska native villages need to be moved. And that's a huge amount. And then you start thinking about, okay, well, the Gulf Coast, we have a lot of people who are gonna have to be moved. And Houston, we had all these people who had no insurance and whose house we got wiped out. South Florida, you know, a storm hits there.  What is your relationship with the government? What is, like in the book, I mentioned this idea of a new, new deal. But there's gonna be a lot of questions about as there is right now in Alaska, what does the state and federal government owe to these tribal communities? Do they just let them sit there and say, you know, sorry, you guys built, you know, they actually will move there in some place, but sometimes by government programs.  You know, and who's- Are the people of Rhode Island gonna pay, or are they gonna be happy to pay for villages in Alaska to move? We will very much want to make sure that villages in Rhode Island- Right, yeah, get the same consideration. I mean, you look at the map and there is an enormous amount of Rhode Island territory that goes underwater in this century. And there is an awful lot of what is now mainland that becomes islands. We become a Rhode Island archipelago. And you can bet that Rhode Islanders are gonna be interested in making sure that whatever gets done for this, that they get their share of it. So, and that's gonna be true down the Atlantic coast. It's gonna be true in Florida. The problem is when you stop picking out individual villages and say, okay, we're gonna treat everybody alike here, your number jumps into multiple, multiple trillions of dollars. And then you get all the people up and say, okay, wait a minute, what's up with that? One thing that we got our crop insurance, but I'm a farmer in Iowa and I don't tend to pay for that. So it does create a lot of political tension and it's going to be very challenging and people are gonna be mad as hell. The sooner we start dealing with it though, it's never gonna be easy. And we should never pretend that it will be, but it only gets harder. Right. And at least in America, we have the potential for trying to, because we have so much wealth and so many resources and so much ability to design and engineer and invent. If you are the equivalent of those villages and you're on the coast of Kogo or if you're on the coast of Malaysia or if you're on the coast of Bangladesh, you've got all those same problems plus virtually no resource to help you with it. And if that's not a recipe for getting people mad and turning them to ideologies that scorn capitalism and democracies that fail to prevent this, I think we're asking for it in that sense. I mean, maybe that's already part of what's going on right now worldwide in this sort of global crisis of governance. We have about 20 minutes for Q&A, right, Tonya? Okay, if you've got two quick questions, do your audience. Sorry, we over talked. Yeah, well, there's just so much to talk about. So if you would tell your name in your affiliation and try to make the question quick and we'll bank a few. Incredibly important, particularly where, I mean, the founding fathers set up this country with a safe guard for when the executive and legislative branches were corrupted by what they would have called factions and we would now call special interests and that is the courts and specifically juries which were designed to be protected against special interest influence in a whole variety of ways like it's illegal to tamper with them and you get a new one every time so you can't bribe a repeat performer and all of that. So I think it's going to be incredibly important what happens in our courts to getting this right and holding the people who've done misdeeds to account in ways that we cannot do now in Congress specifically because of their power and their misuse of that power. Do we have any more questions back? Please identify yourselves. The main thing that I want to say is that there's a way to fight back against the rising sea and that is a number of ways. One, flood the Katara Depression and enormous area in Northwest Egypt below sea level, 300 or 400 feet below sea level. Can you pose this as a question please? Yeah, I wonder what your thoughts are on this. It's a giant area of land mass below sea level only 40 miles from the coast in the Mediterranean. The other area is the Dead Sea, 1300 feet below sea level. That could be flooded. Let's talk about it in Israel as a way of providing water for irrigation expanding the Dead Sea, but it's only on paper. That's as far as it goes. And another way of handling things is to go right direct to the Greenland ice mass and break it up and use it for bottled water, something that the world needs. Thanks. Well, you know, I mean, there's a lot of these sort of mega engineering scenarios that are always talked about. I think the idea of, you know, in cities they build flood squares, right? Where they, in Rotterdam, there's that same idea that you were talking about in the Dead Sea or something where when there's a big flood, the water goes in there and it's stored there until it can drain out. But I think that the notion that we're going to resolve sea level rise by digging up basically a hole that's big enough to hold the water that's gonna rise is just not real, not feasible. I mean, I just think it's, I don't think there's a big engineering fix like that. I mean, I do think actually, I'll be very brief about this, but I actually do think that geoengineering, the idea of reflecting some sunlight away to slow the melt of the ice is possible. And that there's a lot of downsides to that. I wrote a whole book about it. I would encourage you to look at it. But I think that's where the big technical fix is going to come. People are going to start to say, we need to start flying some airplanes up there, put a little artificial volcano. Basically building an artificial volcano. Reflect away one or two percent of the sunlight, slow the melt, give us some more time to deal with this. It's a bad idea for a lot of reasons, good idea for some reasons, but that's where the technical fix is gonna come in, I think. We're kind of fighting against human nature a little bit here that I was struck that throughout your book, story after story, people would come to the conclusion, well, we'll figure it out. And that they'll be an answer. My favorite moment is I was at the 100th anniversary of Miami Beach, big party on the beach, it was really fun. And the mayor of, the party's on the beach in Miami, tend to be, the mayor of Miami beach got up and gave a speech and saying, oh, you know, there's all this gloom and doom, you know, people saying, we've been here 100 years and we're not gonna be here another 100 years. But I'm here to tell you, we're gonna have a 200th anniversary. And he holds up his hand, he's got his apple watch. And he says, if someone would have told me 30 years ago that I was gonna have a watch on my hand or I could text my kids or, you know, and check the news and, you know, surf the internet on my wrist, I would have told them they were crazy. And it's the same kind of Yankee ingenuity that's gonna solve this problem. But, you know, that's a happy idea, but it's an order of magnitude different kinds of thinking required to make an apple watch than it is to solve a problem like sea level rise. And I think there's a lot of misapplication of technological optimism in that sense. Although I am, it's ecological optimism. And I share. I am optimistic in a number of ways, but I do think that sea level rise is a call to action in particular about the oceans. Because sea level rise is caused primarily by warming. And when they're warming, other things are happening that create big disturbances that we're not used to in human experience. And we're also acidifying them at a phenomenal astounding rate as the CO2 gets absorbed into the seas. And we're also filling them with plastic at such a rate that it's really now hard to find a plastic-free oyster or clam anywhere. So this is kind of a moment for us to reboot our sense of responsibility about our oceans. They are not infinite waste dumps that we have no accountability for. We really have to change our thinking and sea level rise as kind of a leading indicator as they forcibly intrude their way into our home saying, hey, listen to us. And by the way, we owe them a lot because we're talking about two degrees centigrade being our upper limit, which is probably too high. Without the oceans cooling off, what we've done with the carbon emissions, we'd be at over 30 degrees. And at that point, we're talking about a true planetary emergency. And yes, very dramatic consequences. Reverting to a state of nature for many people.  And again, your book does not end that way. Well, I'm not, no, I mean, I'm not optimist that we're gonna stop the seas from rising. I mean, I think rising and falling of the seas is the fundamental rhythm of life on this planet. And I've been going on as long as this planet has been here, and we're not gonna stop that. And we need to realize that and live with that. And I'm a technological optimist in the sense that I think that we're going to, this movement toward clean energy that you're talking about, I think is going to happen. The economic incentives are so huge. It's so clearly the direction the world's going. I'm totally an optimist in the sense of thinking that we'll move to clean and renewable power much faster than we think we will, despite the horrors that's going on right now, of the kind of regression that fossil fuels. But I do not think that that's going, that's not going to stop the seas from rising. We're gonna have to deal with this. The reason the book is called The Water Will Come is because we're not, even if we go, everyone goes to skateboards tomorrow, turns in their SUVs and goes to skateboards, we're still gonna have to deal with significant sea level rise. And we're not gonna stop that. And so we need to have two conversations at once. We need to have this conversation about how do we cut emissions as quickly as possible for all kinds of reasons, sea level rise is just one of them, ocean acidification, of course, all these other reasons, but we also need to start thinking really seriously about how we're gonna deal with life on our coast and how we're gonna move infrastructure around and some of this long-term planning that has to happen or it's just gonna be, as one person in my book says, a kind of Mad Max scenario on the coast. Any last words, Senator? I'll end on those. Mine were about the oceans. Okay. Well, join me in thanking our speakers and coming by a book. Thank you. Good book. Thank you.


Practically speaking what do you think needs to happen to see that global rollout become a reality? In 2020 the world did come together, coordinated through the World Health Organization. It brought together many of the world's governments, it brought together many of the world's philanthropy and it brought together many of the world's industry and agencies. It's there in order to make sure that the scientific advances of 2020 are now made available and benefit the whole world in an equitable way that brings the pandemic to an end and allows economies to get growing again. And it is that combination of the world coming together under the auspices of WHO in order to make fair inequitable access that brings the pandemic to a close that will allow education to go back, it'll allow economies to regrow and of course it will protect people's lives.


Okay, great, thank you very much for giving me some time to speak to you about some things that we are working on. I'm going to take off from the point of secondary findings and not likely for the reasons you might expect, but I think we fell into this as part of our program and it taught us things that we were surprised to learn and I think are actually useful and helpful for us thinking about how we want to go forward in this realm of research. A couple of minor distinctions here, the distinction of secondary findings from incidental findings is an important one, the former being an intentional search for actionable mutations, much like several of the projects that Gayle described. And the key thing here is that the search for those is independent of the indication for why the sequencing was done in the first place. And those are distinct from incidental which are sort of arbitrary inadvertent discoveries of variants stumbling upon them, et cetera. And suffice it to say, I can summarize a fair amount of angst in a short sentence to say these have been fairly controversial, much derided and often actively avoided part of genomics research and I'm thinking we need to change that because in fact secondary findings are predictive genomic medicine. I would suggest that this is exactly what we want to be doing is going out and finding disease susceptibility in situations where we otherwise might not have even had a reason to ask the question if it was there or not. All right, so precision medicine, predictive medicine, genomic medicine is part of precision medicine. This notion of tailoring risks to individual risk, tailing treatments to individual risk profiles, stratifying risk of disease, stratifying natural history, variation complications, prognosis, treatment responses, et cetera, maximizing efficacy of interventions, minimizing off-target or side effects. And I would say that what this is all about is shifting from a phenotype first approach to a genome first approach and using the genome to tell us what we should be doing, both in the research realm as well as ultimately in the clinical context. And what that will start to look like is having genomic data first and then following that with iterative post hoc phenotyping that is driven by the sequence. It is not driven by the concerns or the questions of the patient or the clinician. That's a bit radical. It makes some people very uncomfortable, but I think this is a activity that we have to do. We sort of stumbled on this originally back a few years ago when we were working with a wonderful collaborator at our institute, Chuck Venditti, who works on typical pediatric onset organic acidemias, combined malonic and methyl malonic acidemia. We set out to figure out what the cause of this was. And this was at the time what we were studying was an autosomal recessive disorder that involved childhood organic acidosis, severe metabolic decompensation, CNS infarction, irreversible stroke, coma, and sometimes death. This is a fairly typical severe pediatric onset metabolic acidosis disorder. So we sequenced a trio, followed it up with validation, Chuck did beautiful functional work and found that it was caused by mutations in a gene called ACSF3. So that's now the very well-established old-fashioned paradigm of how you find a mutation that causes a rare disease. We actually took another step there, which is we wanted to know because this is a subset of a metabolic acidosis phenotype, how common could this disease actually be? So we went into ClinSeq data. And ClinSeq data, as I mentioned, we started in 2006, had about 1,000 samples of people that we had exome data on. So we just went and asked a simple question, what is the carrier rate of that disease and that population from which we could back calculate the frequency of the disease? And so sifting through the ClinSeq data, we came upon a patient who was homozygous for one of the variants that one of the kids had who had the severe metabolic acidosis decomposition and stroke and said, well, that's probably like those variants that Gail mentioned in HGMD, lots of people, including probably us, have made mistakes and incorrectly attributed causation to variants that are in fact benign and were coincidentally present in people with the disease. But in ClinSeq, we have the opportunity to go back and re-phenotype people. So we have the opportunity to go back and ask a question that we never thought to ask when we put the study together, which is, could a patient in ClinSeq have any attributes of combined malonic and methyl malonic acidemia? So we brought the patient in and did testing on her and showed that she had at the age of 66 years old, about 100 times the upper limit of normal of methyl malonic acid in her plasma, about 100 times the upper limit of malonic acid. And then when we scanned her, she had multiple scattered small infarcts that are imaging signal-wise very similar to the strokes that the kids get when they decompensate in the nursery. And then we interviewed her and asked her more questions about her history. Turns out she had a lot of unexplained late onset neurological symptoms. So what did we learn? What we learned is that our pre-hoc conception of what we thought that disease was, was completely wrong. We thought it was just a pediatric onset, severe metabolic decompensation, stroke, and death disease. But it is, in fact, more than that. It is a disease that can present throughout the live spectrum. And we had just never before been aware of that. And no one thought to ask that question until we looked at the patient which was triggered by the genome variants. And so what this told us is we have the ability to do a genome-first ascertainment approach to research that allows us to get beyond some of our ascertainment biases and come to a full understanding of what the genotype-phenotype spectrum is, which is, of course, the essential prerequisite to understanding genotype-phenotype correlations. You have to know what the spectrum of disease is. We've extended that through a number of other genes, collaborating with various groups to look and to identify rare forms of late onset diabetes and cardiac symptoms. And then the secondary findings work that we started, which I would suggest actually opened this field originally by screening our exomes. Back when we only had 500 in some exomes, individuals ascertained for possible cardiovascular disease. We asked the question, what fraction of them have inherited susceptibility to cancer should be unrelated to why they were ascertained for cardiac disease? And in fact, we found a substantial frequency of that. We followed that up with papers on both cardiac dysrhythmias and hypertrophic and dilated cardiomyopathy. And then the most recent one is screening for malignant hyperthermia, classic drug-gene interaction phenotype inhibits. And Gail mentioned this paper and validating this in a broad way across the genome, with the exception that one of the things that we did in these studies is we actually went back and re-phenotyped the individuals for the traits. And this is limited in the ability to do that. But then we wanted to take an even larger step away from phenotype. And again, let the genome tell us what we should be looking at. And so what we did is we said, let's look across the genome for all null variants that our participants might have. This was done in a general way by the 1,000 Genomes project previously. But again, we wanted to couple it to phenotyping. So we searched the exomes for all null variants, then filtered that for genes that are known or have there's good evidence for the gene function being mediated by haploinsufficiency as its mechanism of disease, limited it to things that are plausibly related to disease and not just benign traits. And then whatever variant the participant had, we would go back and phenotype for them irrespective of what it was. And I will tell you the important thing about this is nearly all of the traits that we phenotyped them for. We had no pre-hoc data. And we had to create that post hoc. So that's what this post hoc phenotyping is about. What our result was showed that we have about 50% yield of disease. That is, for any participant who has a loss of function mutations in a gene that appears to have that as a mechanism of disease, half the time they had the phenotype and half the time they did not. The half who did comprise between 2% and 3% of our cohort, which is a number that is much, much higher than I predicted would have been there. And most of those and individuals were not previously diagnosed with these diseases. And I would have to say, if anything, this is probably an underestimate because for sure we don't know all the genes who act in this way. This is obviously a subset of mutations. We're ignoring missense mutations, which are arguably harder to interpret. But there's many more of them there. Our phenotyping was pretty conservative, as well as the fact that we are sequencing adults here. Everyone we sequenced was over the age of 45. And as you all know, loss of function mutations that cause severe disorders often have severe morbidity and mortality in childhood that would not allow them to survive to the age of 45 to be in a research study such as ours. So what have we learned from this? The hypothesis testing model for research absolutely positively works is a fantastic paradigm for approaching scientific questions and should not in any way be limited or supplanted by what we're proposing here. But I would suggest that it can be complemented by what we're proposing to do. And that hypothesis generating research using iterative post hoc phenotyping of patients is essential for us to understand the predictive power of genomics for precision or predictive medicine going forward. We have to have an unbiased ascertainment of phenotypes in order to understand the full spectrum of genotype-phenotype relationships. And this concept of genomic secondary findings was established by this work. The rate we estimated back in about three or four years ago between 2% to 4% has been borne out by several subsequent studies. I would say that what we're thinking about focusing on is that we need to expand and scale this concept of hypothesis generating research. Because I think this is where the payoff will be for us. Genomics has completely revolutionized how we think about basic scientific research. And it has been slower to change how we think about clinical research. Yet I think there is an opportunity there to do that. How we will do that is not a small task. It is harder to change clinicians' minds about how things are than it is basic scientists. They're a conservative bunch. What do we need to do that? We need cohorts that are thoroughly consented for this style and approach to research. They have to be very highly motivated. Some of our participants, it's actually amazing what they will consent to allow us to do to answer questions that may have no relevance to them. It's quite startling. And we need creative and motivated investigators who are willing to do this kind of work to break down the paradigms that we have and move forward. We can envision this going forward in two ways. We're thinking about putting together a combined super cohort within the NIH Intramural Program of adding variants from multiple investigators, cohorts into a pooled bio resource that would consist of volunteers, samples, and genotypes. And then opening that up for investigators basic scientists to go through those data, look for variants and genes of interest to them, request samples, and then get samples from these volunteers to do their basic science research studies on, again, genomically ascertaining the variants that they want to study. And you can also envision, obviously, as I explained how we could do a clinical translational version of this, which is to have investigators queering that database, make study requests, and then have secondary studies performed and those participants, and then feed those results back to investigators so that they can have their questions answered in this hypothesis-generating approach. We also need to push this into clinical space. So I think we have plenty of data, Gail outlined a lot of data that shows good results and validity of findings and approaches that these approaches can be potentially fruitful today in clinical practice in some specific circumstances. We're pushing that out into the NIH Clinical Center, where we are starting a two-track program where we provide sequencing research resources to investigators. And at the same time, use those same data to mine them for secondary actionable clinical findings and return those to research participants so that these researchers can be free to focus on the research that they want to do and they have others take care of this notion of the secondary findings and get this practice and mindset out into the clinical community because, again, it's hard to change how people do things. So my conclusion is I think we need to think genomically in clinical research and that's a much, much easier thing to do than it is to say because, again, these paradigms are hard to change. Hypothesis-generating research I would suggest is a valid, useful, and complementary approach to hypothesis-testing research and I think if we're going to take genomics to the next stage, this is where I think the excitement is, where the opportunities are, and how we can begin to answer some really exciting new questions and make precision medicine actually work. I'll stop there. Thank you for your attention.